Bediha AKMEŞE, Yüksel ALTUN, Senem ŞANLI, Nurullah ŞANLI

Antiülser İlaçlardan Famotidin, Nizatidin ve Ranitidin’nin Ayrışma Sabitlerinin RP-LC Tayini ve Dozaj Formlarından Kantitatif olarak Belirlenmesi

Ayrışma sabiti değeri pKa , farklı pH değerinde, bir ilaç molekülünün iyonlaşma derecesini tahmin etmek için önemli bir parametredir. Bu çalışmada, Famotidin, Ranitidin ve Nizatidin’in farklı yüzdelerdeki asetonitril-su ikili karışımlarındaki %10, %15, %20, v/v pKa değerleri, sıvı kromatografisi yöntemi RPLC alıkonma faktörü ve hareketli faz pH değişimi ile belirlenmiştir. Hesaplanan pK değerlerinden incelenen bileşiklerin su ortamı pKa değerleri, asetonitrilin mol kesri kullanılarak tahmin edilmiştir. Ayrıca, alıkonma faktörü ve su-asetonitril hareketli fazının pH’sı arasında kurulan ilişki optimum ayırma koşulunun belirlenmesi için kullanılmıştır. Optimize edilmiş koşulu valide etmek için, Famotidin, Ranitidin ve Nizatidin kendi dozaj formlarından incelenmiştir. X-Terra C-18 ters-faz kolonu 250 x 4.6 mm ID, 5 um partikül , geliştirilen yöntem için tercih edilmiştir. Hareketli faz olarak asetonitril-metanol-su 10:6:84, fosfat tamponu pH: 6.5 , 210 ve 320 nm dalga boylarında diyot dizi algılama sistemi ayrım koşulları olarak kullanılmıştır. Çalışılan koşullarda Famotidin’in tayin sınırı 0.5678 ug/mL, Ranitidin ve Nizatidin için sırasıyla 0.3100 ug/mL ve 1.3144 ug/mL bulunmuştur. Doğrusallık, kesinlik, doğruluk, duyarlılık sınırı ve kantitatif tayin sınırı parametreleri, ABD Farmakopesine göre incelenmiştir

Anahtar Kelimeler:

Antiülser ilaçlar, Famotidin, Ranitidin, Nizatidin, pKa, HPLC, Methot validasyonu.

RP-LC Determination of Dissociation Constants and Quantitative Estimation of Antiulcer drugs, Famotidine, Nizatidine and Ranitidine in their Dosage Forms

Dissociation constant value pKa is key parameter for predicting the extent of the ionization of a drug molecule at different pH. In this study, pKa values of famotidine, ranitidine and nizatidine in different percentages of acetonitrile-water binary mixtures 10%, 15%, and 20%, v/v were determined from the mobile phase pH dependence of retention factor with reverse phase liquid chromatographic method RPLC . From calculated pKa values, the aqueous pKa values of studied compounds were estimated by mole fraction of acetonitrile. Moreover, the correlation established between retention factor and the pH of the water-acetonitrile mobile phase was used to determination of optimum separation condition. In order to validate the optimized condition, famotidine, ranitidine and nizatidine were studied in their dosage forms. A X-Terra C-18 reverse-phase column 250x4.6mm I.D., 5 μm particles was preferred to carry out the developed method. Mobile phase of acetonit- rile-methanol-water 10:6:84, phosphate buffer pH: 6.5 and diode array detection system at wavelengths 210 and 320 nm were used as separation conditions. Under studied conditions detection limits of 0.5678 μg/mL for famotidine, 0.3100 μg/mL for ranitidine and 1.3144 μg/mL for nizatidine were found. The parameters, linearity, precision, accuracy, limit of detection, and limit of quantitation were studied according to U.S. Pharmacopoeia.

Keywords:

Antiulcer Drugs, Famotidine, Ranitidine, Nizatidine, pKa, HPLC, Method validation,

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