Vorikonazol’ ün İnfüzyon Çözeltisi ve Tabletten Valide Edilmiş Kromatografik Tayini

Yıl 2013, Sayı: 2, 149 - 162, 01.06.2013

Ayşegül Doğan Nursabah E. Başcı

Öz

Vorikonazol VOR immün sistemi baskılanmış hastalarda oluşabilecek invazif aspergilloz tedavisinde kullanılan önemli bir ilaçtır. Bu çalışmada, intravenöz infüzyon ve tablet formülasyonlarından VOR tayini için bir ultra akış sıvı kromatografisi UFLC yöntemi geliştirildi ve ICH rehberlerine uygun olarak valide edilmiştir. İç standart Fenazopiridin IS ile birlikte VOR analizi ACE Excel 2 C18 50 mm x 3 mm id, 2 um analitik kolonu kullanılarak gerçekleştirilmiştir. Bileşenler metanol ve su 50: 50, v/v içeren hareketli faz ile 0.40 mL/dk akış hızında elüe edildi. Dizi diyot dedektör dalga boyu 255 nm olarak ayarlanmıştır. Bu kromatografik şartlar altında VOR ve IS alikonma zamanları sırasıyla 6.09 and 7.35 dk ’dır. VOR için LOD ve LOQ değerleri 50 ng/mL and 100 ng/mL olarak bulunmuştur. Geliştirilen metot VOR için 0.5 - 100 μg/mL aralığında doğrusaldır. Gün içi- günler arası çalışmalarda en yüksek BSS değeri %1.81 olarak bulunmuştur. VOR için ortalama geri kazanım 100.64 ± 0.48% RSD: 1.18%, n=6 dır. Intravenöz infüzyon ve tablet preparasyonlardan VOR analizi için geliştirilmiş yöntemin; farklı analizci ve kromatografik koşullarında küçük değişiklikler açısından, sağlam ve dayanıklı olduğu bulunmuştur. Geliştirilen yöntemin farmakopelerde belirtilen kriterlere dayanan sistem uygunluk değerleri, VOR’un intravenöz infüzyon ve tablet preparasyonlardan tayini için uygun olduğunu ortaya koymaktadır. VOR analizi için geliştirilen ve valide edilen UFLC yönteminin uzun dönem güvenirlik çalışmaları Shewhard kalite kontrol kartları ile gösterilmiştir. Yöntem rutin kalite kontrol çalışmaları için basit, duyarlı, kesin, doğru olup düşük akış hızından dolayı az solvent kullanımı ile ucuzdur.

Anahtar Kelimeler

Vorikonazol, sıvı kromatografisi LC, fenazopiridin, sistem uygunluk, kalite kontrol kartları

A Fully Validated Chromatographic Determination of Voriconazole from Infusion Solution and Tablet

Öz

VOR is a major drug used in the treatment of invasive aspergillosis, which may occur in immunocompromised patients. In this study, an ultra flow liquid chromatographic UFLC method for determination of VOR in intravenous infusion and tablet preparations was developed and fully validated according to the ICH guidelines. The analysis of VOR together with internal standard Phenazoprydine IS was performed using an analytical column of ACE Excel 2 C18 50 mm x 3 mm i.d., 2 μm . Substances were eluted by a mobile phase consisted of methanol and water 50: 50, v/v at a flow rate of 0.40 mL/min. Diode array detector was set to 255 nm. Under these chromatographic conditions retention times of VOR and IS were 6.09 and 7.35 min, respectively. LOD and LOQ values for VOR were found to be 50 ng/mL and 100 ng/mL. Developed method was linear over the range from 0.5 to 100 μg/mL VOR. The highest RSD value was calculated as 1.81% in inter-day and intra-day studies. The mean recovery for VOR was 100.64 ± 0.48% RSD: 1.18%, n = 6 . Developed method for the analysis of VOR in intravenous infusion and tablet preparations was found to be rugged and robust in terms of different anaylst and minor changes in chromatographic conditions. System suitability values of developed method on the basis of criteria stated in pharmacopeias were over the limit values suggesting that was suitable in order to determine VOR in its intravenous infusion and tablet preparations. The long term reliability of the results from developed and fully validated UFLC method presented here was demonstrated via Shewhard’s quality control chart of VOR. Thus, developed UFLC method was simple, sensitive, precise, accurate and cost reduced with low solvent consumption because of its low flow rate for routine quality controls.

Anahtar Kelimeler

voriconazol, liquid chromatography LC, phenazoprydine, system suitability, quality control chart

Kaynakça

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