Estradiol valerat ve dienogest'in farmasötik preparatlarda aynı anda miktar tayinleri

Bu tez kapsaminda; dienogest (DNG) ve estradiol valerat (EV) iceren bir karisimda her iki maddenin ayni anda miktar tayininin yapilabilmesi icin yeni yontemler gelistirilmesi amaciyla calismalar yapilmistir. Calismalarda spektrofotometrik analizler temel alinmis ve 1. turev spektrofotometri (D), spektrofotometrik verilerin temel bilesen regresyonu (TBR) ve kismi en kucuk kareler (KEK) yontemleriyle analizi kullanilmistir.D yonteminde, DNG + EV karisiminin metanol ? su (3:1) icerisindeki cozeltilerinin 200 ? 400 nm arasindaki spektrumlarinin 1. turevinde, DNG icin 328.8 nm' de, EV icin ise 258.4 nm'de analitik sinyaller okunmustur (??= 2 nm, skala faktoru = 30). TBR ve KEK yontemlerinde ise, DNG icin metanol ? su (3:1) icerisindeki cozeltilerinin UV spektrumunlarinin (0. derece) 300 - 350 nm'ler arasindaki bolgede ?? = 1 nm olarak 51 adet dalga boyundaki absorbanslari, EV icin 260-300 nm'ler arasindaki bolgede ?? = 1 nm olarak 41 adet dalga boyundaki absorbanslari okunmus ve TBR ve KEK ile analizleri yapilmistir. Yontemlerdeki ortalama % geri kazanim ve % bagil standart sapma degerleri sirasiyla DNG icin; D'de % 99.28 ve % 0.98, TBR'de % 99.33 ve % 0.34, KEK'de % 99.18 ve % 0.26, EV icin; D'de % 98.56 ve % 0.96, TBR'de % 100.48 ve % 1.58, KEK'de % 100.54 ve % 1.58 olarak bulunmustur. Yontemlerdeki calisma araliklarinin D'de DNG icin 2.0 ? 24.0 ?g/mL, EV icin 10.0 ? 275.0 ?g/mL oldugu, TBR ve KEK'de DNG icin 2.0 ? 24.0 ?g/mL, EV icin 20.0 ? 270.0 ?g/mL oldugu saptanmistir. Gelistirilen bu uc spektrofotometrik yontem Turkiye ilac piyasasinda bulunan draje preparatina basariyla uygulanmistir. Ayrica yeni bir YPSK yontemi gelistirilmistir ki yontemde kolon olarak ACE C8 ters faz kolonu, mobil faz olarak asetonitril ? amonyum nitrat (pH: 5.4, 0.03 M) (70:30 h/h) kullanilmis ve deteksiyon 280 nm'de yapilmistir. Ic standart olarak siproteron asetat secilmistir. Yontemde alikonma zamanlari DNG icin 1.85 dakika, siproteron asetat icin 3.01 dakika ve EV icin 5.95 dakikadir. Yontemdeki ortalama % geri kazanim ve % bagil standart sapma degerleri sirasiyla DNG icin % 101.10 ve % 0.49, EV icin % 100.32 ve % 1.18 olarak bulunmustur. Yontemdeki calisma araliginin DNG icin 3.0  45.0 g/mL EV icin 18.0 ? 100.0 ?g/mL oldugu saptanmistir. Gelistirilen YPSK yontemi de ayni preparata uygulanmis ve elde edilen sonuclar istatistiksel olarak birbirleriyle karsilastirilmistir.AbstractIn the scope of this thesis, studies were conducted in order to develop new methods for the simultaneous determination of dienogest (DNG) and estradiol valerate (EV) in their binary mixture. In the studies; spectrophotometric analysis were essential and first derivative spectrophotometry (D), principle component regression (PCR) and partial least squares (PLS) methods were used in the analysis.In D method, analytical signals were measured at 328.8 nm for DNG, and 258.4 nm for EV in the first derivative spectra of the solution of DNG + EV mixture in methanol ? water (3:1) in 200 ? 400 nm range (?? = 2 nm, scaling factor = 30). In PCR and PLS methods, absorbances were measured at 51 wavelengths between 300-350 nm (?? = 1 nm) for DNG and at 41 wavelengths between 260-300 nm (?? = 1 nm) for EV in original absorption spectra of DNG + EV mixture in methanol ? water (3:1) and, PCR and PLS analysis were achieved. For DNG; mean recoveries and relative standard deviations were found as % 99.28 and % 0.98 in D; % 99.33 and % 0.34 in PCR; % 99.18 and % 0.26 in PLS methods respectively. They are % 98.56 and % 0.96 in D; % 100.48 and % 1.58 in PCR; %100.54 and % 1.58 in PLS for EV respectively. Working ranges were 2.0 ? 24.0 ?g/mL in D, PCR and PLS for DNG. It is 10.0 ? 275.0 ?g/mL in D and 20 ? 270 ?g/mL in PCR and PLS for EV. These three methods were successfully applied to a sugar coated tablet marketed in Turkey. Moreover we developed an HPLC method in which ACE C8 reverse phase column and acetonitril ? ammonium nitrate (pH: 5.4, 0.03 M) (70:30 v/v) mobil phase was used and 280 nm was selected for detection. Cyproteron acetate were chosen as internal standard. Retention times were 1.85 min. for DNG, 3.01 min. for cyproteron acetate and 5.95 min. for EV. Mean recoveries and relative standard deviations are % 101.10 and % 0.49 for DNG; % 100.32 and % 1.18 for EV respectively. In HPLC method, working ranges were found as 3.0 ? 45.0 g/mL for DNG and 18.0 ? 100.0 g/mL for EV. HPLC method was also applied to the same formulation selected and the results were compared with each other statistically.