Engin KOÇAK, Mustafa ÇELEBİER, Sacide ALTINÖZ

RP-HPLC’ nin Rosuvastatin Kalsiyumun İyonlaşma Sabitlerinin Bulunmasında Kullanımı

Bir ilaç molekülünün iyonlaşma sabiti pKa , o ilacın biyofarmasötik davranışını etkileyen en önemli fizikokimyasal parametrelerden biridir. Bu çalışamda, rosuvastatin kalsiyumun iyonlaşma sabiti değerleri RP-HPLC kullanılarak tespit edilmiştir. Rosuvastatin kalsiyum elüsyonu C18 kolon ACE 125x4,6 mm, 5 μm kullanılırken farklı pH değerlerine ayarlanmış asetonitril:fosfat tamponu 40 mM 50:50 h/h hareketli faz olarak kullanılarak gerçekleştirilmiştir. Akış hızı 1 mL dak-1 olarak ayarlanmıştır ve enjeksiyon hacmi 20 μL’ dir. Dedektör 205 nm dalgaboyunda ölçüm yapmıştır. İyonlaşma sabiti değerleri, kapasite faktörü ile hareketli faz pH değerelri arasındaki ilişkiden yola çıkılarak bulunmuştur. Böylece elde edilen sigmoidal eğrilerden rosuvastatin kalsiyuma ait üç farklı iyonlaşma sabiti değeri sırasıyla 3,7; 4,8 ve 6,6 olarak bulunmuştur.

Anahtar Kelimeler:

Rosuvastatin, HPLC, pKa, iyonlaşma sabiti

Application of RP-HPLC for Determination of the Dissociation Constants of Rosuvastatin Calcium

The acid-base dissociation constant pKa of a drug is a key physicochemical parameter influencing many biopharmaceutical characteristics. In this work, dissociation constant values of rosuvastatin calcium were determined by using RP-HPLC method. The elution of rosuvastatin calcium was achieved by using C18 column ACE 125x4,6 mm, 5 μm while the mobile phase was acetonitrile: phosphate buffer 40 mM 50:50 v/v at various pH values. The flow rate was 1 mL min-1 and the injection volume was 20 μL. The detector was set at 205 nm wavelength. Dissociation constant values were obtained through the relationship between the capacity factors and the pH values of the mobile phases. Thus, three ionization steps were properly observed from the sigmoidal curves and the dissociation constant values were found to be 3.7, 4.8 and 5.6, respectively.

Keywords:

Rosuvastatin, HPLC, pKa, dissociation constant,

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