Factorized vs. Normalized Spectra: Comparative Spectrophotometric Approaches for Enhancing the Resolution of Zero-Order Absorption Spectra of Olanzapine and Fluoxetine in Mixtures | 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 Factorized vs. Normalized Spectra: Comparative Spectrophotometric Approaches for Enhancing the Resolution of Zero-Order Absorption Spectra of Olanzapine and Fluoxetine in Mixtures Khaled Hesham, Hend Z. Yamani, Shereen M. Tawakkol, Lobna A. Hussein, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7659193/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Feb, 2026 Read the published version in BMC Chemistry → Version 1 posted 12 You are reading this latest preprint version Abstract Simple, accurate and precise UV spectrophotometric methods were developed and validated for simultaneous determination of olanzapine (OLA) and fluoxetine (FLU) in both bulk powders and combined pharmaceutical formulations, without any prior separation steps. The methods employed advanced mathematical manipulation techniques using both the Constant Multiplication Method (CM) coupled with Spectrum Subtraction (SS) and the Factorized Zero Order Method (FZM) also coupled with SS. These approaches utilized normalized and factorized spectra, respectively, to resolve the overlapping spectral profiles of the two drugs. Unlike conventional methods in literature like derivative spectrophotometry, our approach enabled the extraction of each component in its original zero-order form, exhibiting spectral features identical to those of pure standards, which enhances accuracy and precision. A direct comparative evaluation of CM–SS and FZM–SS is presented, highlighting their respective analytical merits. The proposed methods demonstrated linearity over concentration ranges of 1.5–14 µg/mL, and 3.5–35 µg/mL for OLA and FLU, respectively. The proposed methods were successfully applied for the simultaneous determination of OLA and FLU in synthetic mixtures and in their combined dosage form with very good accuracy and precision. Furthermore, the environmental and practical merits of the methods were evaluated through the principles of Green Analytical Chemistry (GAC) and White Analytical Chemistry (WAC). The greenness assessment of the proposed spectrophotometric method was evaluated by the Analytical Greenness Metric (AGREE). The overall method performance, including validation efficiency, ecological impact, and practicality, was systematically evaluated using the RGB-based WAC approach. Olanzapine Fluoxetine Constant multiplication method Factorized zero order method Normalized Spectrum Factorized spectrum Full Text Additional Declarations No competing interests reported. Table 1 to 4 are available in the Supplementary Files section. Supplementary Files FinalTablesOLAFLU.docx Cite Share Download PDF Status: Published Journal Publication published 24 Feb, 2026 Read the published version in BMC Chemistry → Version 1 posted Editorial decision: Revision requested 06 Oct, 2025 Reviews received at journal 03 Oct, 2025 Reviews received at journal 30 Sep, 2025 Reviewers agreed at journal 30 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviewers invited by journal 29 Sep, 2025 Editor invited by journal 24 Sep, 2025 Editor assigned by journal 24 Sep, 2025 Submission checks completed at journal 24 Sep, 2025 First submitted to journal 19 Sep, 2025 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. 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