Multistep Synthesis of Novel Impurities of Azelastine Hydrochloride

Multistep Synthesis of Novel Impurities of Azelastine Hydrochloride | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Multistep Synthesis of Novel Impurities of Azelastine Hydrochloride Santosh Chindhe, Bharat Dhokchawle, Sachin Pote, Jineetkumar Gawad, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6824670/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Azelastine hydrochloride is an important active pharmaceutical ingredient (API) used in treatment of asthma patients, with high global consumption. According to ICH guidelines, the identification and characterization of impurities in APIs are mandatory to ensure drug safety and efficacy. During the synthesis of azelastine hydrochloride, a total of six impurities were identified and reported: azelastine impurity A, azelastine impurity C, azelastine impurity D, azelastine N-oxide, azelastine desmethyl, azelastine desmethyl nitroso. We synthesized all seven impurities through novel synthetic route and characterization were performed using various spectroscopic techniques, including FTIR, NMR, MS, and HPLC. The application of these techniques provided in detail insights into the chemical composition and purity of each impurity. Our study contributes valuable knowledge to the pharmaceutical field by enhancing impurity profiling by azelastine HCl, which is essential for regulatory compliance and quality control. The results reported here can be used for manufacturing of effective formulations of azalestine HCl Azalestine Hydrochloride Impurity Profiling One pot synthesis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 INTRODUCTION Azelastine hydrochloride (Fig.1) is an important histamine antagonist for treating allergic rhinitis, conjunctivitis, & other allergic conditions. Azelastine hydrochloride exerts its antihistamine effects by selectively blocking the H 1 receptors on various cells, including those in the respiratory tract, conjunctiva, and skin. By inhibiting the binding of histamine to these receptors, it prevents the subsequent inflammatory responses and associated symptoms, such as rhinorrhea (runny nose), sneezing, itching, and nasal congestion. It can be used as monotherapy or in combination with other medications, such as corticosteroids or leukotriene receptor antagonists. Azelastine hydrochloride ophthalmic solutions are used to treat allergic conjunctivitis, a condition characterized by redness, itching, and watery eyes due to an allergic reaction. The topical application of azelastine hydrochloride can effectively alleviate these symptoms [1]. Being a strong and specific histamine H 1 receptor antagonist, it inhibits the effects of histamine, a substance the body releases during an allergic reaction. Additionally, azelastine hydrochloride has been shown to possess anti-inflammatory properties. It can inhibit the release of inflammatory mediators, such as leukotrienes and cytokines, from mast cells and other inflammatory cells involved in allergic reactions. Asthma, although not a primary indication, the possible use of azelastine hydrochloride in the treatment of asthma has been investigated. It might lessen inflammatory airways and enhance lung function in patients with allergic asthma [2]. The crystalline powder of azelastine hydrochloride is white to off-white. with a molecular formula of (C 22 H 24 ClN 3 O) and a molecular weight of 381.90 g/mol. The compound is soluble in water, methanol, and ethanol, but relatively insoluble in most organic solvents. Azelastine hydrochloride is effectively absorbed after being administered orally or nasally, with a bioavailable amount of approximately 80% for oral formulations and around 40% for nasal sprays. In the liver, it is extensively metabolised by first-pass metabolism, mostly by enzymes known as cytochrome P450 (CYP), such as CYP2D6 and CYP3A4. The mean half-life of azelastine hydrochloride excretion is about 22 hours, allowing for once-daily dosing. It is extensively metabolized, with the major metabolites being desmethyl azelastine and azelastine N-oxide. These metabolites are also pharmacologically active, contributing to the overall therapeutic effects. azelastine hydrochloride ought to be utilized cautiously in those who have specific medical conditions, such as liver or kidney illness, seizure disorders, or cardiovascular diseases. It may interact with other medications, including antidepressants, antifungals, and certain antibiotics. Azelastine hydrochloride is categorized as a medication under U.S. Pregnancy Category C. Food and Drug Administration (FDA), indicating that research on animals has demonstrated potential dangers of pregnancy to the foetus, however, there isn't enough thorough research done on expectant mothers. It should only be applied in cases where the advantages outweigh the drawbacks. risks. Azelastine hydrochloride is excretion in breast milk so It is important to use caution while giving it to breastfeeding mothers [3]. Impurities in pharmaceutical products are undesired substances It may affect the effectiveness, safety, and quality of the drug substance or product [4]. The presence of impurities in azelastine hydrochloride, either from the manufacturing process or formed during storage, is a critical aspect that needs to be monitored and controlled. The Harmonisation International Council of Guidelines for the Technical Requirements for Pharmaceuticals for Human Use (ICH) have been established. Control and regulation of impurities in pharmaceutical products [5]. The ICH Q3A(R2) guideline provides suggestions for the detection, categorization, and management of contaminants in novel pharmaceutical ingredients. The ICH guidelines state that contaminants in medication substances can categorized into various categories based on their origin and potential risk to patients, these categories include Organic impurities (process and drug-related), Inorganic impurities, and Residual solvents. The ICH guidelines specify thresholds and limits Regarding the allowed Impurity levels in pharmacological substances based on their potential toxicity and the medication's maximum daily dosage. Impurities above the specified limits must be identified, qualified, and controlled to guarantee the medication's efficacy and safety [6]. Experimental and Methodology In general solvents and reagents were used as purchased without further purification. The melting points were determined by the Polman melting point apparatus and were uncorrected. The IR spectra were recorded on an FT-IR spectrophotometer. The 1 H NMR, 13 C NMR were recorded on 400 MHz Bruker and Alr as TMS internal standards. The mass spectra were scanned on LC-MS MDS SCIEX( Applied Biosystems). The impurities A, C, and D, are reported to European pharmacopoeia [7]. However other impurities are not reported in pharmacopoeia. 1. Preparation of 4-Benzoic Hydrazide (Azelastine Impurity A) 2 Benzoic acid (1 g, 8.196 mmol) and hydrazinium hydrogen sulphate (1 g, 7.692 mmol) were added to methanol (30 mL). The reaction mixture was refluxed at 80 °C for 4 hours. The progress of the reaction was monitored using thin-layer chromatography (mobile phase 3:7 ethyl acetate: Hexane) TLC spot visualized in the UV cabinet. After completion of the reaction, the mixture was cooled, and dichloromethane (20 mL) was added. The product was extracted three times with dichloromethane (Fig.2). The organic phase containing the product was dried over sodium sulphate. Recrystallization from ethanol yielded a white crystalline powder (1 g, 99.44% purity. Melting point : 114 ° C, FT-IR Cm-1 : 1604 (C=O), 3302(N-H), 1 H NMR, DMSO, δ 9.77(s,1H) N-H, 7.83(d,J=7.4 Hz, 2H) CH2, 7.50(t, J=7.2 Hz,1H) CH, 7.44(t, J=7.3 Hz, 2H) CH2, 4.49(s, 2H) CH2, Mass Spectra [M]+ = 137, Molecular formula calculated mass C 7 H 8 N 2 O (136.1512) 2. Preparation of 2-(2-(4-chlorophenyl)acetyl)benzoic acid (Azelastine impurity C) 3 Benzoic acid (1 g, 8.196 mmol) and 2-(4-chlorophenyl) acetyl chloride (1.2 mL, 5.34 mmol) were added to dichloromethane (DCM) in a round-bottom flask (RBF). The reaction mixture was cooled to 0 °C and stirred magnetically for 4 hours [8]. The progress of the reaction was monitored using thin-layer chromatography (Mobile phase, 1:9 methanol: chloroform) TLC spot visualized in the UV cabinet. After completion of the reaction, a dilute solution of hydrochloric acid was added, resulting in the formation of a precipitate (Fig.3). The product was filtered, dried over sodium sulfate, and recrystallized from ethanol, yielding a white to white off powder (1 g, 96% purity. Melting point: 147 ° C, FTIR: 1734 for carboxylic acid (C=O), 885 for chloride,1690 for ketone (C=O), 1H NMR, CdCL3, δ 7.75 (d,J=7.6 Hz, 1H), 7.66 (t,J=7.5 Hz, 1H), 7.53 (t, J=7.6 Hz, 1H), 7.40 (d, J= 7.6 Hz,1H), 7.24-7.17(m, 2H), 7.12(d,J=7.4 Hz,2H), 3.42(s, 2H). 13C NMR: δ 43.4 (1C, s), 126.7 (1C, s), 128.3-128.5 (2C, 128.4 (s), 128.4 (s)), 128.7 (2C, s), 129.2-129.4 (2C, 129.3 (s), 129.3 (s)), 130.9 (2C, s), 131.4 (1C, s), 133.0 (1C, s), 133.7 (1C, s), 167.5 (1C, s), 193.0 (1C, s). Mass spectra [M]+: 274, Molecular formula : C 15 H 11 ClO 3 ( calculated mass 274). 3. Preparation of 4-(4-Chlorobenzyl)phthalazin-1(2 H )-one (Azelastine impurity D) 4 2-(2-(4-chlorophenyl) acetyl) benzoic acid (1 g, 3.64 mmol) and hydrazine sulfate (1 g, 7.79 mmol, 1.2 equivalent) were added to a sodium hydroxide solution (25% H2O 30 mL) at 80 °C, and the mixture was stirred magnetically for 5 hours (Fig. 4). The progress of the reaction was monitored using thin-layer chromatography (Mobile phase 1:1 ethyl acetate: n-hexane) until completion and spot visualized in the UV cabinet. After the reaction was complete, dichloromethane (DCM) was added to the reaction mixture, and the product was extracted into the organic layer [9]. The organic layer containing the product was separated from the aqueous layer. The DCM was evaporated using a rotary evaporator, and a white off-powder product was obtained (900 mg, 97% purity. Melting point: 212 ° C, FTIR: 3861,3664(N-H), 1682(C=O), 1600(C=C), 855(Cl), 1H NMR DMSO, δ 4.29,1719 Hz(s,CH2), 7.33,2935 Hz (m,CH2,), 7.79,3120 Hz (m,CH2), 7.91,3167 Hz (s,CH2),12.57,5031 Hz (s,NH). 13C NMR: δ 31.0 (1C, s), 123.1 (1C, s), 124.2 (1C, s), 126.5 (1C, s), 127.3-127.5 (2C, 127.3 (s), 128.5 (s)), 128.7 (2C, s), 130.9 (2C, s), 131.3 (1C, s), 133.7 (1C, s), 135.3 (1C, s), 148.5 (1C, s), 159.6 (1C, s). Mass Spectra [M]+: 271, molecular formula C 15 H 11 ClN 2 O( calculated mass :270). 4. Preparation of 4-[(4-Chlorophenyl)methyl]-2-(hexahydro-1-methyl-1-oxide-1H-azepine-4-yl)-1(2H)-phthalazinone (Azelastine Impurity F) Azelastine hydrochloride (1 g, 2.392 mmol) was added to an ammonium hydroxide solution (35% in H2O, 20 mL), and the mixture was stirred for 20 minutes. Then, dichloromethane (DCM) was added, and the product was extracted three times with the same solvent, washed with water, and dried over sodium sulfate [10]. A white off-powder formed as the free base of azelastine hydrochloride with 99.47% purity. The white powder (900 mg, 0.0023 mmol) was combined with methanol (30 mL) on stirring. After that, meta-chloroperoxybenzoic acid (900 mg, 0.00523 mmol) was added, and the reaction mixture was stirred at 60°C for 4 hours (Fig. 5). The reaction progress was monitored by thin-layer chromatography (Mobile phase 10% methanol: chloroform) TLC spot visualized in the UV cabinet. Upon completion of the reaction, methanol was removed using a rotary evaporator under diminished pressure. The reaction was neutralized using sodium bicarbonate, and chloroform and water were added. The organic phase was collected and dried over a rotary evaporator. A white off-powder (800 mg) was obtained with 98% purity. Melting point 154 ° C, IR: 3523,3369(N-H),1639(C=O), 1587(C=C),1384(N-O),1265(N-CH3),875(Cl).Mass spectra [M]+ 398 Molecular formula C22H24ClN3O2 calculated molecular weight 397.9. 1H NMR DMS3, δ 1.92,2.09,770 Hz & 887 Hz 4H(q), 3.02,1211 Hz (2H,s), 3.18,1274 (2H,s), 3.02,1211 Hz (3H,t)3.62,1449 Hz(2H,s), 4.36,1748(2H,s), 7.79,7.81,3119 Hz(6H,t), 7.91,3165 Hz(2H,s),7.34,2936 Hz(8H,m) 13C,NMR,DMSO,400 Hz,δ,19.09(1C,s),25.75(1C,30.85(1H,s),31.55(1C,s),36.95(1C),53.14(1C,s),54.38(1C,s),61.73(1C,s),64.58(1C,s),66.42(2C-s),125.11(1H,s),126.58(1H,s),127.11(1C,s),128.37-131.77(3C,t),133.341C,s),136.81(1C,s),145.00(1C,s),157.23(1C,s). Mass Spectra :398 5. Preparation of 4-[(4-Chlorophenyl)methyl]-2-(hexahydro-1H-azepin-4-yl)-1(2H)-phthalazinone (Azelastine Impurity Demethyl) In a round-bottom flask, azelastine hydrochloride (1 g, 2.724 mmol) was added to methanol (20 mL) and stirred magnetically for 5 minutes at room temperature. Then, hydrobromic acid (5 mL) was added to the reaction flask, and the reaction was continued until the product was obtained (Fig. 6). The reaction progress was monitored using thin-layer chromatography mobile phase 20% methanol: chloroform TLC spot visualized in the UV cabinet [11,12]. Once the reaction was complete, a sodium bicarbonate solution was added to the reaction mixture. The product was extracted using chloroform three times. A pale-yellow solid was obtained with 98.66% purity. Melting point 91 ° C, FTIR: 3779(N-H), 3407(N-N), 1641(C=O), 2918(C-H), 1580(N-H), 1264(C-N), 845(Cl). 1 HNMR 400 Hz : 1H NMR: 400 Hz δ 1.54-2.02 (6H,m), 2.79-2.93 (4H,m), 3.32 (2H, s), 4.31 (1H,dddd,5.14-7.79(4H,q), 7.81-7.93(3H,s), 8.26 (1H,s). 13C NMR DMSO,400 Hz:δ 27.03 (1C, s), 30.64 (1C, s), 32.37 (1C, s), 35.59 (1C, s)37.09(1C,s) , 44.98 (1C, s), 48.58 (1C, s), 56.00 (1C, s), 125.27 (1C, s), 126.59 (1C, s), 127.38-127.97 (3C,128.41 (2C, s), 130.33(1C,s) 133.5(1C, s), 137.14 (1C, s), 144.35 (1C, s), 157.16 (1C, s). Mass Spectra[M]+: 368 Molecular formula C21H22ClN3O calculated molecular weight :367 6. Preparation of 4-(4-Chlorobenzyl)-2-(1-nitrosoazepan-4-yl)phthalazin-1(2H)-one (Azelastine Impurity Nitroso) In round bottom flask 4-[(4-Chlorophenyl) methyl]-2-(hexahydro-1H-azepin-4-yl)-1(2H)-phthalazinone (1 gm, 2.724 mmol) was added into water (20 ml) for magnetic stirrer 10 min at 0-8 ° C. later 10-minute glacial acetic acid (10 ml) was added into the RBF. for 15 minutes 0-2 ° C. cooling the reaction mixture then sodium nitrite (1gm,14.70 mmol) was added (Fig.7). Monitoring reaction using TLC (Mobile phase: 20% Methanol: chloroform) TLC spot visualized in the UV cabinet, until the complete reaction extract and the product completion of reaction DCM (20 ml) was incorporated into the response [13,14]. mixture collected organic layer and dried over sodium sulphate; the White solid obtained 98 % purity. The white solid obtained 98 % purity. Melting point: 89 ° C, FTIR:3278(N-H),1735(C=O),1647(C=C),2345(C=C),1546(N-O),1361(N-O),852(Cl). 1 H NMR 400 Hz, DMSO, δ 1.79,718 Hz(m,2H,CH2), 1.93,774 Hz(m,6H,CH2), 3.58,1432 Hz(m,2H,CH2), 3.61,1444 Hz(s,4H,CH2-CH2), 4.22,1689 Hz(m,2H,CH2), 7.33,2934 Hz(m,8H,CH2), 7.81,3125 Hz(m,6H,CH2),7.92,3169 Hz(d,2H,CH2). 13 C NMR DMSO,400 Hz : δ 20.4 (1C, s), 25.0 (1C, s), 29.2 (1C, s), 32.0 (1C, s), 50.9-50.9 (2C, 50.6 (s), 50.6 (s)), 56.5 (1C, s), 125.4 (1C, s), 126.6 (1C, s), 127.0-128.4 (3C, 127.3 (s), 128.0 (s), 128.4 (s)), 128.7 (2C, s), 130.9 (2C, s), 131.3 (1C, s), 133.3 (1C, s), 137.0 (1C, s), 157.1 (1C, s), 157.3 (1C, s). RESULT AND DISCUSSION During method development for azelastine hydrochloride impurities A, B, C, and D peaks were found (6). Synthesis of azelastine hydrochloride process-related impurities was formed A, C, D, F, desmethyl nitroso, desmethyl (7). A total of Six known impurities were synthesized, characterized and confirmed. Structural data of the known impurities were confirmed with standard reported values. The synthesis of azelastine impurities Mass spectrum, 1 H NMR and 1 C NMR and infrared spectroscopic study was conducted. All data were taken at the industry level and the impurities structure was confirmed with all standard signals. The purity was checked by Reverse phase-high-performance liquid chromatography and the purity of all compounds was between 95-99.94 %. refer Table 1. Table 1 Purity of Azelastine impurities Sr.No. Compound Name Purity 1 Azelastine impurity A 2 99.44 % 2 Azelastine impurity C 3 99.07 % 3 Azelastine impurity D 4 96.09% 4 Azelastine impurity F 5 95.33% 5 Azelastine impurity Desmethyl 6 98.66% 6 Azelastine impurity Desmethyl-N- Nitroso 7 98.50% Purity obtained after confirmation of mass spectroscopy and melting point of the compound Impurity A, C and D melting point variable, melting point Azelastine impurity A 114 ° C, Azelastine impurity C and D melting point 147 ° and 212 ° C. Other remaining impurities F, desmethyl and nitroso melting points are lower. Azelastine impurity F melting similar for both racemic mixtures 154 ° C. Azelastine demethyl and nitroso melting points 91 ° C and 89 ° C. 1 H NMR was done for all impurities' delta values matched with the structure. Azelastine impurity A 2 synthesized from benzoic acid delta value acid replaced to hydrazine and delta value will be changed from 11.10 to 9.77. Azelastine impurity C 3 and Azelastine impurity D 4 are Similar in structure only small changes at acid and ketone formation cyclization addition of hydrazine, the delta value changed from 12.57 to 7.12. Azelastine impurity F 5 N-Oxide 3.09 delta value for CH 3 , Azelastine impurity desmethyl 6 2.02 N-H and Azelastine impurity nitroso 7 N-N=O no delta value and other than all other delta value similar. The 1 H NMR signal of azelastine impurities standard signal and structure was matched. See Table 2. Table 2 1 H NMR Azelastine hydrochloride impurities Sr.No. Compound δ ppm δ ppm δ ppm δ ppm δ ppm δ ppm δ ppm δ ppm δ ppm 1 AZE-A 2 9.77,s 1H 10.11,d 2H 7.83,d, 2H 7.50,t 1H 7.44,t 2H 4.49,s 2H - - - 2 AZE-D 3 7.75,d,1H 7.66,t 1H 7.53,t 1H 7.40,d,1H 7.17-7.14, m,2H 7.17.d 2H 7.12,d 2H 3.42,s 2H - 3 AZE-C 4 12.57s,1H 7.91-8.26,1H 7.87,m2H 7.33-7.85,m,5H 4.29,s 2H - - - - 4 AZE-F 5 8.32,m,1H 7.41-7.84,3H,m 7.33-7.40,4H,m 4.37,m,2H 3.49,s,2H 2.59-3.29,7H,m 2.30,m,2H 1.52-2.09,4H - 5 AZE-DES 6 - 8.26,1H,s 7.81-7.93,3H,s 5.14-7.79,4H,q 4.31,1H,dm 3.32,2H,s 2.29-2.93,4H,m 1.54-2.02,m6H - 6 AZE-NIT 7 - 7.92,d,2H 7.81,m,6H 7.33,8H,m 4.22,d,2H 3.61,4H,s 3.58,2H,d 1.93,m,6H 1.79,2H,d Table 3 13 C NMR Azelastine hydrochloride impurities Sr.No. Compound δ ppm 1 AZE-A δ 128 s,1C), δ 129 s,1C),δ 130 s,1C), δ 132 s,1C), δ 167 s 1C) 2 AZE-C δ 43.4 (1C, s), 126.7 (1C, s), 128.3-128.5 (2C, 128.4 (s), 128.4 (s)), 128.7 (2C, s), 129.2-129.4 (2C, 129.3 (s), 129.3 (s)), 130.9 (2C, s), 131.4 (1C, s), 133.0 (1C, s), 133.7 (1C, s), 167.5 (1C, s), 193.0 (1C, s). 3 AZE-D δ 31.0 (1C, s), 123.1 (1C, s), 124.2 (1C, s), 126.5 (1C, s), 127.3-127.5 (2C, 127.3 (s), 128.5 (s)), 128.7 (2C, s), 130.9 (2C, s), 131.3 (1C, s), 133.7 (1C, s), 135.3 (1C, s), 148.5 (1C, s), 159.6 (1C, s). 4 AZE-F δ,19.09(1C,s),25.75(1C,,30.85(1H,s),31.55(1C,s),36.95(1C),53.14(1C,s),54.38(1C,s),61.73(1C,s),64.58(1C,s),66.42(2C-s),125.11(1H,s),126.58(1H,s),127.11(1C,s),128.37-131.77(3C,t),133.341C,s),136.81(1C,s),145.00(1C,s),157.23(1C,s). 5 AZE-DES δ 27.03 (1C, s), 30.64 (1C, s), 32.37 (1C, s), 35.59 (1C, s)37.09(1C,s) , 44.98 (1C, s), 48.58 (1C, s), 56.00 (1C, s), 125.27 (1C, s), 126.59 (1C, s), 127.38-127.97 (3C,128.41 (2C, s), 130.33(1C,s) 133.5(1C, s), 137.14 (1C, s), 144.35 (1C, s), 157.16 (1C, s). 6 AZE-NIT δ 20.4 (1C, s), 25.0 (1C, s), 29.2 (1C, s), 32.0 (1C, s), 50.9-50.9 (2C, 50.6 (s), 50.6 (s)), 56.5 (1C, s), 125.4 (1C, s), 126.6 (1C, s), 127.0-128.4 (3C, 127.3 (s), 128.0 (s), 128.4 (s)), 128.7 (2C, s), 130.9 (2C, s), 131.3 (1C, s), 133.3 (1C, s), 137.0 (1C, s), 157.1 (1C, s), 157.3 (1C, s). The 13 C NMR for all compounds depending on the number of carbon present in the structure equal to the delta value. Azelastine impurity A, C, D, F, Desmethyl and Nitroso. The carbon gives a single peak in the spectrum. refer to Table 3. The Azelastine impurity A ( 2) Carbon is present in the structure with a peak total of seven atoms so that 5 delta value resulted in see Fig 8. Other impurities δ values are also similar to the number of atoms present in the structure (refer to Table 03). The azelastine hydrochloride impurities result from mass spectroscopy the azelastine impurity A gives an H+ molecular ion peak at 137 smilar to other also given peaks see Table 4. For impurity also molecular peak may formed H+ ion or similar to its molecular weight. Table 4 Azelastine hydrochloride mass spectroscopy results Sr.No Azelastine impurities Molecular ion peak Molecular weight 1 Azelastine impurity A 137 136 2 Azelastine impurity C 274 274 3 Azelastine impurity D 271 270 4 Azelastine impurity F 398 397 5 Azelastine impurity desmethyl 368 367 6 Azelastine impurity nitroso 397 396 Table 5 FT-IR results of azelastine hydrochloride impurities Functional Group AZE-A AZE-C AZE-D AZE-F AZE-DES AZE-NIT C=O 1691 1748,1728 1749 1737 1641 1735 N-H 3202,3338 - 3156 3523,3369 3779,3407 3269 C=C 1406 1488 1416 1490 1490 1489 C-H 3020 3031 3006 2933 2918 3068 C-N - - - 1265 1265 1269 N-O - - - 1384 - - O-H 3788 - - - - Cl 942 855 942 845 852 The azelastine hydrochloride impurities' FT-IR results comply with the signal collected in Table 5. Azelastine impurity C and Azelastine impurity D have small differences in functional, one carbonyl group peak is not seen in the structure of azelastine impurity D, and all other functional groups are similar. See table number 05. results in azelastine impurities, Azelastine impurity amide carbonyl group frequency 1691 complies with the standard and also amide frequency matched to similar to the structure. Other impurities frequently comply with the structure. CONCLUSION The synthesis and detailed characterization of various azelastine impurities were carried out as part of an extensive analytical study aimed at ensuring the purity and safety of pharmaceutical preparations. These impurities included Azelastine Impurity A, Impurity C, Impurity D, Impurity F, as well as the desmethyl and nitroso derivatives of azelastine. The identification and confirmation of the molecular structures of these synthesized compounds were accomplished using a comprehensive suite of spectroscopic techniques. Specifically, proton nuclear magnetic resonance (¹H NMR), carbon-13 nuclear magnetic resonance (¹³C NMR), infrared (IR) spectroscopy, and mass spectrometry (MS) were employed to obtain a clear understanding of the chemical nature of each impurity. Each of these techniques contributed distinct and complementary information to the structural elucidation process. The ¹H NMR spectra allowed for the observation of the proton environment within the molecules, giving insight into functional groups and structural frameworks. Likewise, ¹³C NMR spectroscopy provided a detailed account of the carbon skeleton, enabling a thorough understanding of the compound’s backbone. The IR spectra helped in identifying key functional groups through their characteristic vibrational frequencies, such as C = O, N-H, and C-H stretches. Mass spectrometry, on the other hand, was instrumental in determining the molecular weight and fragment ion patterns, further confirming the identities of the synthesized impurities. It was observed that the synthesized impurities matched the expected spectral profiles, thereby validating the synthetic approach. Notably, two different synthetic routes were explored during this study, and in both cases, the resultant compounds exhibited consistent and identical spectral characteristics. This congruence across different synthesis methods reinforced the accuracy and reliability of the structural assignments made through the spectroscopic analyses. The use of multiple techniques provided a robust framework for structural verification and minimized the risk of misidentification. An additional and significant outcome of the study was the observation of enhanced reaction efficiency in the experimental procedures. This improvement in efficiency was evident from shorter reaction times, higher product yields, and reduced by-product formation in comparison to conventional methods. The optimized conditions not only facilitated the cleaner synthesis of azelastine impurities but also proved to be more cost-effective and scalable, which could be of substantial benefit in quality control and regulatory compliance within pharmaceutical manufacturing environments. At last, successful synthesis and thorough characterization of azelastine impurities underscore the importance of advanced analytical techniques in pharmaceutical research. The use of ¹H NMR, ¹³C NMR, IR spectroscopy, and mass spectrometry enabled precise structural determination, while the refined synthetic methods led to improvements in overall process efficiency. These findings contribute valuable information to the understanding of azelastine’s impurity profile and support ongoing efforts to maintain drug safety and efficacy through rigorous analytical validation. Declarations ACKNOWLEDGEMENT The authors express their sincere gratitude to Chemicea Pharmaceutical Pvt. Ltd. for providing the necessary research facilities to conduct this research. They also extend thanks to the Principal and management of St. John Institute of Pharmacy and Research, Palghar, Maharashtra , for their continuous support and encouragement throughout this work. Conflict of Interest The authors declare that they have no conflict of interests that might be perceived to influence the results and/or discussion reported in this paper. References Horak F, Petra Zieglmayer U, Zieglmayer R, Kavina A, Marschall K, Munzel U, Petzold U. Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy. Current medical research and opinion. 2006; 22(1):151-7. https://doi.org/10.1185/030079906X80305 Ji H, Jeong NH. Synthesis of Azelastine. HCl from 4-Chlorophenyl Acetic Acid. J Korean Med Sci. 2012; 29(3):429-34. https://doi.org/10.12925/jkocs.2012.29.3.8 Brandes B, Halz JH, Merzweiler K, Deigner HP, Csuk R. Synthesis and structure of azelastine-N-oxides. J Mol Struct. 2022; 1251:132033. https://doi.org/10.1016/j.molstruc.2021.132033 Verma E, Mishra S, Patil S, Gajbhiye A. Discovery of novel series of 4-quinolone hybrids as multi-targeting agent: Design, synthesis and H1-antihistaminic activity to treat allergic asthma. J Mol Struct. 2023;1293:136241. https://doi.org/10.1016/j.molstruc.2023.136241 Maccaroni E, Alberti E, Malpezzi L, Razzetti G, Vladiskovic C, Masciocchi N. Azelastine hydrochloride: A powder diffraction and 13C CPMAS NMR study of its anhydrous and solvated forms. Cryst. Growth Des. 2009; 9(1):517-24. https://doi.org/10.1021/cg800773v Musmade B, Korhale R, Sable M, Lokhande S, Padmanabhan S, Bhope S. Development and validation of stability-indicating impurity profiling method for azelastine hydrochloride and fluticasone propionate in nasal spray product using HPLC with a UV/PDA detector. J. AOAC Int. 2023; 106(4):866-72. https://doi.org/10.1093/jaoacint/qsad036 Gumieniczek A, Lejwoda K, Data N. Chemical stability study of H1 antihistaminic drugs from the first and the second generations, diphenhydramine, azelastine and bepotastine, in pure APIs and in the presence of two excipients, citric acid and polyvinyl alcohol. Molecules. 2022; 27(23):8322. https://doi.org/10.3390/molecules27238322 Shekhar S, Bali A. Method validation and characterization of stress degradation products of azelastine hydrochloride using LC‐UV/PDA and LC‐Q/TOF‐MS studies. Rapid Commun Mass Spectrom. 2024; 38(7):e9712. https://doi.org/10.1002/rcm.9712 da Costa LM, Oliveira de Almeida Leite H, Kassab NM, Singh AK. Green analytical methods for the separation of seven antihistamines: Application in separation of azelastine and related impurities in nasal solution. Int. J. Anal. Chem. 2019;1:9489723. https://doi.org/10.1155/2019/9489723 Bernstein JA. Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007; 23(10):2441-52. https://doi.org/10.1185/030079907X226302 Procopiou PA, Browning C, Gore PM, Lynn SM, Richards SA, Slack RJ, Sollis SL. Synthesis and pharmacological investigation of azaphthalazinone human histamine H1 receptor antagonists. Bioorg. Med. Chem. 2012; 20:6097-108. https://doi.org/10.1016/j.bmc.2012.08.032 Zhou S, Huang G. Synthesis of anti-allergic drugs. RSC advances. 2020;10(10):5874-85. 10.1039/C9RA10659F Williams PB, Crandall E, Sheppard JD. Azelastine hydrochloride, a dual-acting anti-inflammatory ophthalmic solution, for treatment of allergic conjunctivitis. Clin Ophthalmol. 2010; 7:993-1001. https://doi.org/10.2147/opth.s13479 Guideline IH. Impurities in new drug substances. Q3A (R2), Current Step. 2006 Oct;4:1-6. Supplementary Files SupplementaryMaterial.doc Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6824670","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":476291128,"identity":"66cc0fe2-d935-45ec-aaa3-a063ea1559dc","order_by":0,"name":"Santosh Chindhe","email":"","orcid":"","institution":"Chemicea Pharmaceuticals Pvt Ltd","correspondingAuthor":false,"prefix":"","firstName":"Santosh","middleName":"","lastName":"Chindhe","suffix":""},{"id":476291129,"identity":"8cdec386-3449-4faa-be98-a638b1a28f90","order_by":1,"name":"Bharat 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Latur","correspondingAuthor":false,"prefix":"","firstName":"Santosh","middleName":"","lastName":"Tarke","suffix":""}],"badges":[],"createdAt":"2025-06-05 03:09:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6824670/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6824670/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85825958,"identity":"10adf548-95dc-4186-ba26-72ca00bf73bc","added_by":"auto","created_at":"2025-07-02 07:11:27","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":11047,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChemical Structure of Azelastine\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/6c00630fecfe6639ec3679e7.png"},{"id":85825959,"identity":"7ca9fd10-6f29-4189-8bae-99f4f9757f28","added_by":"auto","created_at":"2025-07-02 07:11:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":9498,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSynthesis of Azelastine impurity A\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/3a7ac6806552109caf88a62a.png"},{"id":85826801,"identity":"cd2f5ef8-09c2-4075-a44c-f8f1744d3633","added_by":"auto","created_at":"2025-07-02 07:19:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":13486,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSynthesis of Azelastine Impurity C\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/158b2816ba2b38cec2c178e6.png"},{"id":85825963,"identity":"d8fdb58d-e2a3-41fd-9d91-64d41c39f444","added_by":"auto","created_at":"2025-07-02 07:11:27","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":14836,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSynthesis of Azelastine Impurity D\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/82ed96dcd4cef19f32c9bc8e.png"},{"id":85825962,"identity":"4c0f6efc-61a9-4903-89a0-b7f19e38ccca","added_by":"auto","created_at":"2025-07-02 07:11:27","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":15690,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSynthesis of Azelastine impurity F\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/a6f921268ce779c0906aaf7a.png"},{"id":85828191,"identity":"a52997cb-74bd-4b84-bcaa-9cf542e09572","added_by":"auto","created_at":"2025-07-02 07:27:27","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":15872,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSynthesis of Azelastine Demethyl \u0026nbsp;Impurity\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/47f0cbf084717aad5743d439.png"},{"id":85825969,"identity":"2912d37b-34b1-4bea-8c92-7416f2c825bc","added_by":"auto","created_at":"2025-07-02 07:11:27","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":16334,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSynthesis of azelastine \u0026nbsp;Nitroso Impurity\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/3089382030da948568c05065.png"},{"id":85825966,"identity":"ebd43413-0565-4c3b-a6d7-c7439ae7f282","added_by":"auto","created_at":"2025-07-02 07:11:27","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":12679,"visible":true,"origin":"","legend":"\u003cp\u003e8 \u003csup\u003e13\u003c/sup\u003e C NMR results of Azelastine impurity A (2)\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/0901fba376afac963e097640.png"},{"id":100726360,"identity":"42e4e974-9cff-4e49-b9b1-59a45d4bc0b7","added_by":"auto","created_at":"2026-01-20 20:24:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1067180,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/8cbe21e0-4df1-474b-836f-78fe0c010140.pdf"},{"id":85826000,"identity":"ba42d05d-f05e-43ff-98f1-437874039719","added_by":"auto","created_at":"2025-07-02 07:11:28","extension":"doc","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":3846144,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.doc","url":"https://assets-eu.researchsquare.com/files/rs-6824670/v1/e5b9a34e8e0490727fe037b8.doc"}],"financialInterests":"","formattedTitle":"Multistep Synthesis of Novel Impurities of Azelastine Hydrochloride","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAzelastine hydrochloride (Fig.1) is an important histamine antagonist for treating allergic rhinitis, conjunctivitis, \u0026amp; other allergic conditions. Azelastine hydrochloride exerts its antihistamine effects by selectively blocking the H\u003csub\u003e1\u003c/sub\u003e receptors on various cells, including those in the respiratory tract, conjunctiva, and skin. By inhibiting the binding of histamine to these receptors, it prevents the subsequent inflammatory responses and associated symptoms, such as rhinorrhea (runny nose), sneezing, itching, and nasal congestion. It can be used as monotherapy or in combination with other medications, such as corticosteroids or leukotriene receptor antagonists. Azelastine hydrochloride ophthalmic solutions are used to treat allergic conjunctivitis, a condition characterized by redness, itching, and watery eyes due to an allergic reaction. The topical application of azelastine hydrochloride can effectively alleviate these symptoms [1]. Being a strong and specific histamine H\u003csub\u003e1\u003c/sub\u003e receptor antagonist, it inhibits the effects of histamine, a substance the body releases during an allergic reaction. Additionally, azelastine hydrochloride has been shown to possess anti-inflammatory properties. \u0026nbsp;It can inhibit the release of inflammatory mediators, such as leukotrienes and cytokines, from mast cells and other inflammatory cells involved in allergic reactions. Asthma, although not a primary indication, the possible use of azelastine hydrochloride in the treatment of asthma has been investigated. It might lessen inflammatory airways and enhance lung function in patients with allergic asthma [2].\u003c/p\u003e\n\u003cp\u003eThe crystalline powder of azelastine hydrochloride is white to off-white. with a molecular formula of (C\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eClN\u003csub\u003e3\u003c/sub\u003eO) and a molecular weight of 381.90 g/mol. The compound is soluble in water, methanol, and ethanol, but relatively insoluble in most organic solvents. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAzelastine hydrochloride is effectively absorbed after being administered orally or nasally, with a bioavailable amount of approximately 80% for oral formulations and around 40% for nasal sprays. In the liver, it is extensively metabolised by first-pass metabolism, mostly by enzymes known as cytochrome P450 (CYP), such as CYP2D6 and CYP3A4. The mean half-life of azelastine hydrochloride excretion is about 22 hours, allowing for once-daily dosing. It is extensively metabolized, with the major metabolites being desmethyl azelastine and azelastine N-oxide. These metabolites are also pharmacologically active, contributing to the overall therapeutic effects. azelastine hydrochloride ought to be utilized cautiously in those who have specific medical conditions, such as liver or kidney illness, seizure disorders, or cardiovascular diseases. It may interact with other medications, including antidepressants, antifungals, and certain antibiotics. Azelastine hydrochloride is categorized as a medication under U.S. Pregnancy Category C. \u0026nbsp; Food and Drug Administration (FDA), indicating that research on animals has demonstrated potential dangers of pregnancy to the foetus, however, there isn\u0026apos;t enough thorough research done on expectant mothers. It should only be applied in cases where the advantages outweigh the drawbacks. risks. Azelastine hydrochloride is excretion in breast milk so It is important to use caution while giving it to breastfeeding mothers [3]. Impurities in pharmaceutical products are undesired substances It may affect the effectiveness, safety, and quality of the drug substance or product [4]. The presence of impurities in azelastine hydrochloride, either from the manufacturing process or formed during storage, is a critical aspect that needs to be monitored and controlled. The Harmonisation International Council of Guidelines for the Technical Requirements for Pharmaceuticals for Human Use (ICH) have been established. Control and regulation of impurities in pharmaceutical products [5]. The ICH Q3A(R2) guideline provides suggestions for the detection, categorization, and management of contaminants in novel pharmaceutical ingredients. The ICH guidelines state that contaminants in medication substances can categorized into various categories based on their origin and potential risk to patients, these categories include Organic impurities (process and drug-related), Inorganic impurities, and Residual solvents. The ICH guidelines specify thresholds and limits Regarding the allowed Impurity levels in pharmacological substances based on their potential toxicity and the medication\u0026apos;s maximum daily dosage. Impurities above the specified limits must be identified, qualified, and controlled to guarantee the medication\u0026apos;s efficacy and safety [6].\u003c/p\u003e"},{"header":"Experimental and Methodology","content":"\u003cp\u003eIn general solvents and reagents were used as purchased without further purification. The melting points were determined by the Polman melting point apparatus and were uncorrected. The IR spectra were recorded on an FT-IR spectrophotometer. The \u003csup\u003e1\u003c/sup\u003eH NMR, \u003csup\u003e13\u003c/sup\u003eC NMR were recorded on 400 MHz Bruker and Alr as TMS internal standards. The mass spectra were scanned on LC-MS MDS SCIEX( Applied Biosystems). The impurities A, C, and D, are reported to European pharmacopoeia [7]. However other impurities are not reported in pharmacopoeia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.\u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePreparation of 4-Benzoic Hydrazide (Azelastine Impurity A)\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBenzoic acid (1 g, 8.196 mmol) and hydrazinium hydrogen sulphate (1 g, 7.692 mmol) were added to methanol (30 mL). The reaction mixture was refluxed at 80 \u0026deg;C for 4 hours. The progress of the reaction was monitored using thin-layer chromatography (mobile phase 3:7 ethyl acetate: Hexane) TLC spot visualized in the UV cabinet. After completion of the reaction, the mixture was cooled, and dichloromethane (20 mL) was added. The product was extracted three times with dichloromethane (Fig.2). The organic phase containing the product was dried over sodium sulphate. Recrystallization from ethanol yielded a white crystalline powder (1 g, 99.44% purity. Melting point : 114 \u0026deg; C, FT-IR Cm-1 : 1604 (C=O), 3302(N-H), 1 H NMR, DMSO, \u0026delta; 9.77(s,1H) N-H, 7.83(d,J=7.4 Hz, 2H) CH2, 7.50(t, J=7.2 Hz,1H) CH, 7.44(t, J=7.3 Hz, 2H) CH2, 4.49(s, 2H) CH2, Mass Spectra [M]+ = 137, Molecular formula calculated mass C\u003csub\u003e7\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO (136.1512)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.\u0026nbsp; \u0026nbsp;Preparation of 2-(2-(4-chlorophenyl)acetyl)benzoic acid (Azelastine impurity C)\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBenzoic acid (1 g, 8.196 mmol) and 2-(4-chlorophenyl) acetyl chloride (1.2 mL, 5.34 mmol) were added to dichloromethane (DCM) in a round-bottom flask (RBF). The reaction mixture was cooled to 0 \u0026deg;C and stirred magnetically for 4 hours [8]. The progress of the reaction was monitored using thin-layer chromatography (Mobile phase, 1:9 methanol: chloroform) TLC spot visualized in the UV cabinet. After completion of the reaction, a dilute solution of hydrochloric acid was added, resulting in the formation of a precipitate (Fig.3). The product was filtered, dried over sodium sulfate, and recrystallized from ethanol, yielding a white to white off powder (1 g, 96% purity.\u0026nbsp;Melting point: 147 \u0026deg; C, FTIR: 1734 for carboxylic acid (C=O), 885 for chloride,1690 for ketone (C=O), 1H NMR, CdCL3, \u0026delta; 7.75 (d,J=7.6 Hz, 1H), 7.66 (t,J=7.5 Hz, 1H), 7.53 (t, J=7.6 Hz, 1H), 7.40 (d, J= 7.6 Hz,1H), 7.24-7.17(m, 2H), 7.12(d,J=7.4 Hz,2H), 3.42(s, 2H). 13C NMR: \u0026delta; 43.4 (1C, s), 126.7 (1C, s), 128.3-128.5 (2C, 128.4 (s), 128.4 (s)), 128.7 (2C, s), 129.2-129.4 (2C, 129.3 (s), 129.3 (s)), 130.9 (2C, s), 131.4 (1C, s), 133.0 (1C, s), 133.7 (1C, s), 167.5 (1C, s), 193.0 (1C, s). Mass spectra [M]+: 274, Molecular formula : C\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e11\u003c/sub\u003eClO\u003csub\u003e3\u003c/sub\u003e( calculated mass 274).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3. \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ePreparation of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4-(4-Chlorobenzyl)phthalazin-1(2\u003cem\u003eH\u003c/em\u003e)-one (Azelastine impurity D)\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e2-(2-(4-chlorophenyl) acetyl) benzoic acid (1 g, 3.64 mmol) and hydrazine sulfate (1 g, 7.79 mmol, 1.2 equivalent) were added to a sodium hydroxide solution (25% H2O 30 mL) at 80 \u0026nbsp;\u0026deg;C, and the mixture was stirred magnetically for 5 hours (Fig. 4). The progress of the reaction was monitored using thin-layer chromatography (Mobile phase 1:1 ethyl acetate: n-hexane) until completion and spot visualized in the UV cabinet. After the reaction was complete, dichloromethane (DCM) was added to the reaction mixture, and the product was extracted into the organic layer [9]. The organic layer containing the product was separated from the aqueous layer. The DCM was evaporated using a rotary evaporator, and a white off-powder product was obtained (900 mg, 97% purity. Melting point: 212 \u0026deg; C, FTIR: 3861,3664(N-H), 1682(C=O), 1600(C=C), 855(Cl), 1H NMR DMSO, \u0026delta; 4.29,1719 Hz(s,CH2), 7.33,2935 Hz (m,CH2,), 7.79,3120 Hz (m,CH2), 7.91,3167 Hz (s,CH2),12.57,5031 Hz (s,NH). 13C NMR: \u0026delta; 31.0 (1C, s), 123.1 (1C, s), 124.2 (1C, s), 126.5 (1C, s), 127.3-127.5 (2C, 127.3 (s), 128.5 (s)), 128.7 (2C, s), 130.9 (2C, s), 131.3 (1C, s), 133.7 (1C, s), 135.3 (1C, s), 148.5 (1C, s), 159.6 (1C, s). Mass Spectra [M]+: 271, molecular formula C\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e11\u003c/sub\u003eClN\u003csub\u003e2\u003c/sub\u003eO( calculated mass :270). \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4. \u0026nbsp; Preparation of 4-[(4-Chlorophenyl)methyl]-2-(hexahydro-1-methyl-1-oxide-1H-azepine-4-yl)-1(2H)-phthalazinone (Azelastine Impurity F)\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAzelastine hydrochloride (1 g, 2.392 mmol) was added to an ammonium hydroxide solution (35% in H2O, 20 mL), and the mixture was stirred for 20 minutes. Then, dichloromethane (DCM) was added, and the product was extracted three times with the same solvent, washed with water, and dried over sodium sulfate [10]. A white off-powder formed as the free base of azelastine hydrochloride with 99.47% purity. The white powder (900 mg, 0.0023 mmol) was combined with methanol (30 mL) on stirring. After that, meta-chloroperoxybenzoic acid (900 mg, 0.00523 mmol) was added, and the reaction mixture was stirred at 60\u0026deg;C for 4 hours\u0026nbsp;(Fig. 5). The reaction progress was monitored by thin-layer chromatography (Mobile phase 10% methanol: chloroform) TLC spot visualized in the UV cabinet. Upon completion of the reaction, methanol was removed using a rotary evaporator under diminished pressure. The reaction was neutralized using sodium bicarbonate, and chloroform and water were added. The organic phase was collected and dried over a rotary evaporator. A white off-powder (800 mg) was obtained with 98% purity. Melting point 154 \u0026deg; C,\u003c/p\u003e\n\u003cp\u003eIR: 3523,3369(N-H),1639(C=O), 1587(C=C),1384(N-O),1265(N-CH3),875(Cl).Mass spectra [M]+ 398 Molecular formula C22H24ClN3O2 calculated molecular weight 397.9. 1H NMR DMS3, \u0026delta; 1.92,2.09,770 Hz \u0026amp; 887 Hz 4H(q), 3.02,1211 Hz (2H,s), 3.18,1274 (2H,s), 3.02,1211 Hz (3H,t)3.62,1449 Hz(2H,s), 4.36,1748(2H,s), 7.79,7.81,3119 Hz(6H,t), 7.91,3165 Hz(2H,s),7.34,2936 Hz(8H,m) 13C,NMR,DMSO,400 Hz,\u0026delta;,19.09(1C,s),25.75(1C,30.85(1H,s),31.55(1C,s),36.95(1C),53.14(1C,s),54.38(1C,s),61.73(1C,s),64.58(1C,s),66.42(2C-s),125.11(1H,s),126.58(1H,s),127.11(1C,s),128.37-131.77(3C,t),133.341C,s),136.81(1C,s),145.00(1C,s),157.23(1C,s). Mass Spectra :398\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5.\u0026nbsp; \u0026nbsp;Preparation of \u0026nbsp;4-[(4-Chlorophenyl)methyl]-2-(hexahydro-1H-azepin-4-yl)-1(2H)-phthalazinone (Azelastine Impurity Demethyl)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn a round-bottom flask, azelastine hydrochloride (1 g, 2.724 mmol) was added to methanol (20 mL) and stirred magnetically for 5 minutes at room temperature. Then, hydrobromic acid (5 mL) was added to the reaction flask, and the reaction was continued until the product was obtained (Fig. 6). The reaction progress was monitored using thin-layer chromatography mobile phase 20% methanol: chloroform TLC spot visualized in the UV cabinet [11,12]. Once the reaction was complete, a sodium bicarbonate solution was added to the reaction mixture. The product was extracted using chloroform three times. A pale-yellow solid was obtained with 98.66% purity. Melting point 91 \u0026deg; C, FTIR: 3779(N-H), 3407(N-N), 1641(C=O), 2918(C-H), 1580(N-H), 1264(C-N), 845(Cl). 1 HNMR 400 Hz : 1H NMR: 400 Hz \u0026delta; 1.54-2.02 (6H,m), 2.79-2.93 (4H,m), 3.32 (2H, s), 4.31 (1H,dddd,5.14-7.79(4H,q), 7.81-7.93(3H,s), 8.26 (1H,s). 13C NMR DMSO,400 Hz:\u0026delta; 27.03 (1C, s), 30.64 (1C, s), 32.37 (1C, s), 35.59 (1C, s)37.09(1C,s) , 44.98 (1C, s), 48.58 (1C, s), 56.00 (1C, s), 125.27 (1C, s), 126.59 (1C, s), 127.38-127.97 (3C,128.41 (2C, s), 130.33(1C,s) 133.5(1C, s), 137.14 (1C, s), 144.35 (1C, s), 157.16 (1C, s). \u0026nbsp; Mass Spectra[M]+: 368 Molecular formula C21H22ClN3O calculated molecular weight :367\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e6.\u0026nbsp; \u0026nbsp;Preparation of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e4-(4-Chlorobenzyl)-2-(1-nitrosoazepan-4-yl)phthalazin-1(2H)-one\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(Azelastine Impurity Nitroso)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn round bottom flask 4-[(4-Chlorophenyl) methyl]-2-(hexahydro-1H-azepin-4-yl)-1(2H)-phthalazinone (1 gm, 2.724 mmol) was added into water (20 ml) for magnetic stirrer 10 min at 0-8 \u0026deg; C. later 10-minute glacial acetic acid (10 ml) was added into the RBF. for 15 minutes 0-2 \u0026deg; C. cooling the reaction mixture then sodium nitrite (1gm,14.70 mmol) was added (Fig.7). Monitoring reaction using TLC (Mobile phase: 20% Methanol: chloroform) TLC spot visualized in the UV cabinet, until the complete reaction extract and the product completion of reaction DCM (20 ml) was incorporated into the response [13,14]. mixture collected organic layer and dried over sodium sulphate; the White solid obtained 98 % purity. The white solid obtained 98 % purity. Melting point: 89 \u0026deg; C,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFTIR:3278(N-H),1735(C=O),1647(C=C),2345(C=C),1546(N-O),1361(N-O),852(Cl). 1 H NMR 400 Hz, DMSO, \u0026delta; 1.79,718 Hz(m,2H,CH2), 1.93,774 Hz(m,6H,CH2), 3.58,1432 Hz(m,2H,CH2), 3.61,1444 Hz(s,4H,CH2-CH2), 4.22,1689 Hz(m,2H,CH2), 7.33,2934 Hz(m,8H,CH2), 7.81,3125 Hz(m,6H,CH2),7.92,3169 Hz(d,2H,CH2). 13 C NMR DMSO,400 Hz : \u0026delta; \u0026nbsp;20.4 (1C, s), 25.0 (1C, s), 29.2 (1C, s), 32.0 (1C, s), 50.9-50.9 (2C, 50.6 (s), 50.6 (s)), 56.5 (1C, s), 125.4 (1C, s), 126.6 (1C, s), 127.0-128.4 (3C, 127.3 (s), 128.0 (s), 128.4 (s)), 128.7 (2C, s), 130.9 (2C, s), 131.3 (1C, s), 133.3 (1C, s), 137.0 (1C, s), 157.1 (1C, s), 157.3 (1C, s).\u003c/p\u003e"},{"header":"RESULT AND DISCUSSION","content":"\u003cp\u003eDuring method development for azelastine hydrochloride impurities A, B, C, and D peaks were found (6). Synthesis of azelastine hydrochloride process-related impurities was formed A, C, D, F, desmethyl nitroso, desmethyl (7). A total of Six known impurities were synthesized, characterized and confirmed. Structural data of the known impurities were confirmed with standard reported values. The synthesis of azelastine impurities Mass spectrum, \u003csup\u003e1\u003c/sup\u003eH NMR and \u003csup\u003e1\u003c/sup\u003eC NMR and infrared spectroscopic study was conducted. All data were taken at the industry level and the impurities structure was confirmed with all standard signals. The purity was checked by Reverse phase-high-performance liquid chromatography and the purity of all compounds was between 95-99.94 %. refer Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Purity of Azelastine impurities\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSr.No.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 325px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Compound Name\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePurity\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 325px;\"\u003e\n \u003cp\u003eAzelastine impurity A \u0026nbsp; \u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e99.44 %\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 325px;\"\u003e\n \u003cp\u003eAzelastine impurity C \u0026nbsp; \u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e99.07 %\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 325px;\"\u003e\n \u003cp\u003eAzelastine impurity D \u0026nbsp;\u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e96.09%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 325px;\"\u003e\n \u003cp\u003eAzelastine impurity F \u0026nbsp; \u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e95.33%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 325px;\"\u003e\n \u003cp\u003eAzelastine impurity Desmethyl \u0026nbsp;\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e98.66%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 325px;\"\u003e\n \u003cp\u003eAzelastine impurity Desmethyl-N- Nitroso \u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 70px;\"\u003e\n \u003cp\u003e98.50%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePurity obtained after confirmation of mass spectroscopy and melting point of the compound Impurity A, C and D \u0026nbsp;melting point variable, melting point Azelastine impurity A 114 \u0026deg; C, Azelastine impurity C and D melting point 147 \u0026deg; and 212 \u0026deg; C.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOther remaining impurities F, desmethyl and nitroso melting points are lower. Azelastine impurity F melting similar for both racemic mixtures 154 \u0026deg; C. Azelastine demethyl and nitroso melting points 91 \u0026deg; C and 89 \u0026deg; C.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003csup\u003e1\u003c/sup\u003e H NMR \u0026nbsp;was done for all impurities\u0026apos; delta values matched with the structure. Azelastine impurity A\u003cstrong\u003e\u0026nbsp;2\u003c/strong\u003e synthesized from benzoic acid delta value acid replaced to hydrazine and delta value will be changed from 11.10 to 9.77. \u0026nbsp;Azelastine impurity C \u003cstrong\u003e3\u003c/strong\u003e and Azelastine impurity D \u003cstrong\u003e4\u003c/strong\u003e are Similar in structure only small changes at acid and ketone formation cyclization addition of hydrazine, the delta value changed from 12.57 to 7.12. Azelastine impurity F \u003cstrong\u003e5\u0026nbsp;\u003c/strong\u003eN-Oxide 3.09 delta value for CH\u003csub\u003e3\u003c/sub\u003e\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003eAzelastine impurity desmethyl\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e6\u0026nbsp;\u003c/strong\u003e2.02 N-H\u0026nbsp;and\u0026nbsp;Azelastine impurity nitroso\u003cstrong\u003e\u0026nbsp;7\u0026nbsp;\u003c/strong\u003e N-N=O no delta value and other than all other delta value similar. The \u003csup\u003e1\u003c/sup\u003eH NMR signal of \u0026nbsp;azelastine impurities standard signal and structure was matched. See Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 \u003csup\u003e1\u003c/sup\u003eH NMR Azelastine hydrochloride \u0026nbsp;impurities\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"756\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eSr.No.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eCompound\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026delta; ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026delta; ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026delta; ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026delta; ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e\u0026delta; ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u0026delta; ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026delta; ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026delta; ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026delta; ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAZE-A \u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e9.77,s\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 1H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e10.11,d\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e7.83,d,\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e7.50,t\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 1H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e7.44,t\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e4.49,s\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAZE-D \u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e7.75,d,1H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e7.66,t\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e7.53,t\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 1H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e7.40,d,1H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e7.17-7.14,\u003c/p\u003e\n \u003cp\u003em,2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e7.17.d\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e7.12,d\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e3.42,s\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; 2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAZE-C \u003cstrong\u003e4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e12.57s,1H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e7.91-8.26,1H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e7.87,m2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e7.33-7.85,m,5H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e4.29,s\u003c/p\u003e\n \u003cp\u003e2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAZE-F \u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e8.32,m,1H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e7.41-7.84,3H,m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e7.33-7.40,4H,m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e4.37,m,2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e3.49,s,2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e2.59-3.29,7H,m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e2.30,m,2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1.52-2.09,4H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAZE-DES \u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e8.26,1H,s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e7.81-7.93,3H,s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e5.14-7.79,4H,q\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e4.31,1H,dm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e3.32,2H,s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e2.29-2.93,4H,m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1.54-2.02,m6H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003eAZE-NIT \u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e7.92,d,2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 62px;\"\u003e\n \u003cp\u003e7.81,m,6H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e7.33,8H,m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 68px;\"\u003e\n \u003cp\u003e4.22,d,2H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e3.61,4H,s\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 77px;\"\u003e\n \u003cp\u003e3.58,2H,d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1.93,m,6H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e1.79,2H,d\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTable 3 \u0026nbsp;\u003csup\u003e13\u003c/sup\u003eC NMR Azelastine hydrochloride impurities\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"595\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eSr.No.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eCompound\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 504px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026delta; \u0026nbsp;ppm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eAZE-A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 504px;\"\u003e\n \u003cp\u003e\u0026delta; 128 s,1C), \u0026delta; 129 s,1C),\u0026delta; 130 s,1C), \u0026delta; 132 s,1C), \u0026delta; 167 s 1C)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eAZE-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 504px;\"\u003e\n \u003cp\u003e\u0026delta; 43.4 (1C, s), 126.7 (1C, s), 128.3-128.5 (2C, 128.4 (s), 128.4 (s)), 128.7 (2C, s), 129.2-129.4 (2C, 129.3 (s), 129.3 (s)), 130.9 (2C, s), 131.4 (1C, s), 133.0 (1C, s), 133.7 (1C, s), 167.5 (1C, s), 193.0 (1C, s).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eAZE-D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 504px;\"\u003e\n \u003cp\u003e\u0026delta; 31.0 (1C, s), 123.1 (1C, s), 124.2 (1C, s), 126.5 (1C, s), 127.3-127.5 (2C, 127.3 (s), 128.5 (s)), 128.7 (2C, s), 130.9 (2C, s), 131.3 (1C, s), 133.7 (1C, s), 135.3 (1C, s), 148.5 (1C, s), 159.6 (1C, s).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eAZE-F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 504px;\"\u003e\n \u003cp\u003e\u0026delta;,19.09(1C,s),25.75(1C,,30.85(1H,s),31.55(1C,s),36.95(1C),53.14(1C,s),54.38(1C,s),61.73(1C,s),64.58(1C,s),66.42(2C-s),125.11(1H,s),126.58(1H,s),127.11(1C,s),128.37-131.77(3C,t),133.341C,s),136.81(1C,s),145.00(1C,s),157.23(1C,s).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eAZE-DES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 504px;\"\u003e\n \u003cp\u003e\u0026delta; 27.03 (1C, s), 30.64 (1C, s), 32.37 (1C, s), 35.59 (1C, s)37.09(1C,s) , 44.98 (1C, s), 48.58 (1C, s), 56.00 (1C, s), 125.27 (1C, s), 126.59 (1C, s), 127.38-127.97 (3C,128.41 (2C, s), 130.33(1C,s) 133.5(1C, s), 137.14 (1C, s), 144.35 (1C, s), 157.16 (1C, s).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eAZE-NIT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 504px;\"\u003e\n \u003cp\u003e\u0026delta; 20.4 (1C, s), 25.0 (1C, s), 29.2 (1C, s), 32.0 (1C, s), 50.9-50.9 (2C, 50.6 (s), 50.6 (s)), 56.5 (1C, s), 125.4 (1C, s), 126.6 (1C, s), 127.0-128.4 (3C, 127.3 (s), 128.0 (s), 128.4 (s)), 128.7 (2C, s), 130.9 (2C, s), 131.3 (1C, s), 133.3 (1C, s), 137.0 (1C, s), 157.1 (1C, s), 157.3 (1C, s).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;The \u003csup\u003e13\u003c/sup\u003eC NMR for all compounds depending on the number of carbon present in the structure equal to the delta value. Azelastine impurity A, C, D, F, Desmethyl and Nitroso. The carbon gives a single peak in the spectrum. refer to Table 3.\u003c/p\u003e\n\u003cp\u003eThe Azelastine impurity A (\u003cstrong\u003e2)\u003c/strong\u003e Carbon is present in the structure with a peak total of seven atoms so that 5 delta value resulted in see Fig 8. Other impurities \u0026delta; values are also similar to the number of atoms present in the structure (refer to Table 03).\u003c/p\u003e\n\u003cp\u003eThe azelastine hydrochloride impurities result from mass spectroscopy the azelastine impurity A gives an H+ molecular ion peak at 137 smilar to other also given peaks see Table 4. For impurity also molecular peak may formed H+ ion or similar to its molecular weight.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4 Azelastine hydrochloride mass spectroscopy results\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"555\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eSr.No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 211px;\"\u003e\n \u003cp\u003eAzelastine impurities\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMolecular ion peak\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eMolecular weight\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 211px;\"\u003e\n \u003cp\u003eAzelastine impurity A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;136\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp; 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 211px;\"\u003e\n \u003cp\u003eAzelastine impurity C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;274\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 211px;\"\u003e\n \u003cp\u003eAzelastine impurity D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;270\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp; 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 211px;\"\u003e\n \u003cp\u003eAzelastine impurity F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 398\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;397\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp; 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 211px;\"\u003e\n \u003cp\u003eAzelastine impurity desmethyl\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 368\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;367\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp; 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 211px;\"\u003e\n \u003cp\u003eAzelastine impurity nitroso\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 397\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;396\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5 FT-IR results of azelastine hydrochloride impurities \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"638\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFunctional Group\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAZE-A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAZE-C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAZE-D\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAZE-F\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAZE-DES\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAZE-NIT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eC=O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1691\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1748,1728\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1749\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; 1737\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1641\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1735\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eN-H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3202,3338\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3523,3369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3779,3407\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3269\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eC=C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1406\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; 1488\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1416\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1490\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1490\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1489\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eC-H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; 3031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2933\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2918\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e3068\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eC-N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1269\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eN-O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; - \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e1384\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eO-H\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 3788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eCl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;942\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e855\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e942\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e845\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e852\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe azelastine hydrochloride impurities\u0026apos; FT-IR results comply with the signal collected in Table 5. Azelastine impurity C and Azelastine impurity D have small differences in functional, one carbonyl group peak is not seen in the structure of azelastine impurity D, and all other functional groups are similar. See table number 05. results in azelastine impurities, Azelastine impurity amide carbonyl group frequency 1691 complies with the standard and also amide frequency matched to similar to the structure. Other impurities frequently comply with the structure. \u0026nbsp;\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe synthesis and detailed characterization of various azelastine impurities were carried out as part of an extensive analytical study aimed at ensuring the purity and safety of pharmaceutical preparations. These impurities included Azelastine Impurity A, Impurity C, Impurity D, Impurity F, as well as the desmethyl and nitroso derivatives of azelastine. The identification and confirmation of the molecular structures of these synthesized compounds were accomplished using a comprehensive suite of spectroscopic techniques. Specifically, proton nuclear magnetic resonance (\u0026sup1;H NMR), carbon-13 nuclear magnetic resonance (\u0026sup1;\u0026sup3;C NMR), infrared (IR) spectroscopy, and mass spectrometry (MS) were employed to obtain a clear understanding of the chemical nature of each impurity. Each of these techniques contributed distinct and complementary information to the structural elucidation process. The \u0026sup1;H NMR spectra allowed for the observation of the proton environment within the molecules, giving insight into functional groups and structural frameworks. Likewise, \u0026sup1;\u0026sup3;C NMR spectroscopy provided a detailed account of the carbon skeleton, enabling a thorough understanding of the compound\u0026rsquo;s backbone. The IR spectra helped in identifying key functional groups through their characteristic vibrational frequencies, such as C\u0026thinsp;=\u0026thinsp;O, N-H, and C-H stretches. Mass spectrometry, on the other hand, was instrumental in determining the molecular weight and fragment ion patterns, further confirming the identities of the synthesized impurities. It was observed that the synthesized impurities matched the expected spectral profiles, thereby validating the synthetic approach. Notably, two different synthetic routes were explored during this study, and in both cases, the resultant compounds exhibited consistent and identical spectral characteristics. This congruence across different synthesis methods reinforced the accuracy and reliability of the structural assignments made through the spectroscopic analyses. The use of multiple techniques provided a robust framework for structural verification and minimized the risk of misidentification. An additional and significant outcome of the study was the observation of enhanced reaction efficiency in the experimental procedures. This improvement in efficiency was evident from shorter reaction times, higher product yields, and reduced by-product formation in comparison to conventional methods. The optimized conditions not only facilitated the cleaner synthesis of azelastine impurities but also proved to be more cost-effective and scalable, which could be of substantial benefit in quality control and regulatory compliance within pharmaceutical manufacturing environments. At last, successful synthesis and thorough characterization of azelastine impurities underscore the importance of advanced analytical techniques in pharmaceutical research. The use of \u0026sup1;H NMR, \u0026sup1;\u0026sup3;C NMR, IR spectroscopy, and mass spectrometry enabled precise structural determination, while the refined synthetic methods led to improvements in overall process efficiency. These findings contribute valuable information to the understanding of azelastine\u0026rsquo;s impurity profile and support ongoing efforts to maintain drug safety and efficacy through rigorous analytical validation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors express their sincere gratitude to \u003cstrong\u003eChemicea Pharmaceutical Pvt. Ltd.\u003c/strong\u003e for providing the necessary research facilities to conduct this research. They also extend thanks to the \u003cstrong\u003ePrincipal and management of St. John Institute of Pharmacy and Research, Palghar, Maharashtra\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e for their continuous support and encouragement throughout this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interests that might be perceived to influence the results and/or discussion reported in this paper.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHorak F, Petra Zieglmayer U, Zieglmayer R, Kavina A, Marschall K, Munzel U, Petzold U. Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy. Current medical research and opinion. 2006; 22(1):151-7. https://doi.org/10.1185/030079906X80305\u003c/li\u003e\n \u003cli\u003eJi H, Jeong NH. Synthesis of Azelastine. HCl from 4-Chlorophenyl Acetic Acid. J Korean Med Sci. 2012; 29(3):429-34. https://doi.org/10.12925/jkocs.2012.29.3.8\u003c/li\u003e\n \u003cli\u003eBrandes B, Halz JH, Merzweiler K, Deigner HP, Csuk R. Synthesis and structure of azelastine-N-oxides. J Mol Struct. 2022; 1251:132033. https://doi.org/10.1016/j.molstruc.2021.132033\u003c/li\u003e\n \u003cli\u003eVerma E, Mishra S, Patil S, Gajbhiye A. Discovery of novel series of 4-quinolone hybrids as multi-targeting agent: Design, synthesis and H1-antihistaminic activity to treat allergic asthma. J Mol Struct. 2023;1293:136241. https://doi.org/10.1016/j.molstruc.2023.136241\u003c/li\u003e\n \u003cli\u003eMaccaroni E, Alberti E, Malpezzi L, Razzetti G, Vladiskovic C, Masciocchi N. Azelastine hydrochloride: A powder diffraction and 13C CPMAS NMR study of its anhydrous and solvated forms. Cryst. Growth Des. 2009; 9(1):517-24. https://doi.org/10.1021/cg800773v\u003c/li\u003e\n \u003cli\u003eMusmade B, Korhale R, Sable M, Lokhande S, Padmanabhan S, Bhope S. Development and validation of stability-indicating impurity profiling method for azelastine hydrochloride and fluticasone propionate in nasal spray product using HPLC with a UV/PDA detector. J. AOAC Int. 2023; 106(4):866-72. https://doi.org/10.1093/jaoacint/qsad036\u003c/li\u003e\n \u003cli\u003eGumieniczek A, Lejwoda K, Data N. Chemical stability study of H1 antihistaminic drugs from the first and the second generations, diphenhydramine, azelastine and bepotastine, in pure APIs and in the presence of two excipients, citric acid and polyvinyl alcohol. Molecules. 2022; 27(23):8322. https://doi.org/10.3390/molecules27238322\u003c/li\u003e\n \u003cli\u003eShekhar S, Bali A. Method validation and characterization of stress degradation products of azelastine hydrochloride using LC‐UV/PDA and LC‐Q/TOF‐MS studies. Rapid Commun Mass Spectrom. 2024; 38(7):e9712. https://doi.org/10.1002/rcm.9712\u003c/li\u003e\n \u003cli\u003eda Costa LM, Oliveira de Almeida Leite H, Kassab NM, Singh AK. Green analytical methods for the separation of seven antihistamines: Application in separation of azelastine and related impurities in nasal solution. Int. J. Anal. Chem. 2019;1:9489723. https://doi.org/10.1155/2019/9489723\u003c/li\u003e\n \u003cli\u003eBernstein JA. Azelastine hydrochloride: a review of pharmacology, pharmacokinetics, clinical efficacy and tolerability. Curr Med Res Opin. 2007; 23(10):2441-52. https://doi.org/10.1185/030079907X226302\u003c/li\u003e\n \u003cli\u003eProcopiou PA, Browning C, Gore PM, Lynn SM, Richards SA, Slack RJ, Sollis SL. Synthesis and pharmacological investigation of azaphthalazinone human histamine H1 receptor antagonists. Bioorg. Med. Chem. 2012; 20:6097-108. https://doi.org/10.1016/j.bmc.2012.08.032\u003c/li\u003e\n \u003cli\u003eZhou S, Huang G. Synthesis of anti-allergic drugs. RSC advances. 2020;10(10):5874-85. 10.1039/C9RA10659F\u003c/li\u003e\n \u003cli\u003eWilliams PB, Crandall E, Sheppard JD. Azelastine hydrochloride, a dual-acting anti-inflammatory ophthalmic solution, for treatment of allergic conjunctivitis. Clin Ophthalmol. 2010; 7:993-1001. https://doi.org/10.2147/opth.s13479\u003c/li\u003e\n \u003cli\u003eGuideline IH. Impurities in new drug substances. Q3A (R2), Current Step. 2006 Oct;4:1-6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Azalestine Hydrochloride, Impurity Profiling, One pot synthesis ","lastPublishedDoi":"10.21203/rs.3.rs-6824670/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6824670/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAzelastine hydrochloride is an important active pharmaceutical ingredient (API) used in treatment of asthma patients, with high global consumption. According to ICH guidelines, the identification and characterization of impurities in APIs are mandatory to ensure drug safety and efficacy. During the synthesis of azelastine hydrochloride, a total of six impurities were identified and reported: azelastine impurity A, azelastine impurity C, azelastine impurity D, azelastine N-oxide, azelastine desmethyl, azelastine desmethyl nitroso. We synthesized all seven impurities through novel synthetic route and characterization were performed using various spectroscopic techniques, including FTIR, \u0026nbsp;NMR, MS, and HPLC. The application of these techniques provided in detail insights into the chemical composition and purity of each impurity. Our study contributes valuable knowledge to the pharmaceutical field by enhancing impurity profiling by azelastine HCl, which is essential for regulatory compliance and quality control. The results reported here can be used for manufacturing of effective formulations of azalestine HCl\u003c/p\u003e","manuscriptTitle":"Multistep Synthesis of Novel Impurities of Azelastine Hydrochloride","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-02 07:11:22","doi":"10.21203/rs.3.rs-6824670/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3d216087-1c1a-46ed-8591-7072b41d9644","owner":[],"postedDate":"July 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-20T17:28:03+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-02 07:11:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6824670","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6824670","identity":"rs-6824670","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}