FARMASÖTİK DOZAJ FORMUNDAN KAPTOPRİL TAYİNİ İÇİN YENİ STABİLİTE- GÖSTERGELİ RP-HPLC YÖNTEMİNİN YEŞİL PROSEDÜR İNDEKSİ DEĞERLENDİRİLMESİ

Öz

Amaç: Bu çalışmada, yaygın bir ağrı kesici olan parasetamol iç standart olarak kullanarak antihipertansif ilaç kaptopril’in ultra-hassas tayini için yeni bir ters fazlı sıvı kromatografi yönteminin geliştirilmesi amaçlanmıştır. Mobil faz bileşimi, akış hızı, kolon sıcaklığı gibi tüm deneysel koşulların optimizasyonu adım adım gerçekleştirilmiş ve geliştirilen yöntemin yöntem geçerliliği uluslararası validasyon kılavuzlarına göre incelenmiştir. Kalibrasyon aralığı, doğrusallık, tespit limiti, tayin limiti, sağlamlık, ticari tablet numunelerinden doğruluk ve metot stabilitesi detaylı olarak incelenmiştir. Ayrıca geliştirilen yöntemin yeşillik profili, literatürde sıklıkla kullanılan Yeşil Analitik Prosedür İndeksi ve Analitik Yeşillik Hesaplayıcı teknikleri ile değerlendirilmiştir. Gereç ve Yöntem: Kromatografik yöntem, tamamen gözenekli silika materyaller ile doldurulmuş bir XBridge C18 kolonu (25 cm x 4.6 mm ID; 5 µm) ile gerçekleştirildi. Tüm analizler, 1.5 ml dk-1 akış hızında asetonitril:5 mM, pH 7.0 amonyum asetat çözeltisi (50:50, v/v) içeren bir mobil faz ile izokratik olarak yapıldı. Enjeksiyon hacmi 5 µl idi ve kolon, bir kolon fırınında 25°C’de sabit tutuldu. Kolon eluatı 220 nm’de izlendi. Optimize edilmiş koşullar altında, kaptopril ve parasetamolün alıkonma süreleri sırasıyla yaklaşık 1.59 ve 2.0 dakika olmuştur. Sonuç ve Tartışma: Bu çalışma, tablet numunelerinde kaptopril tayini için tam olarak doğrulanmış, basit, hassas, doğru, doğrusal, kesin ve tekrar üretilebilir bir ters fazlı sıvı kromatografi yöntemini tanımlamıştır. Optimal deneysel koşullar altında lineer aralık 0.5-200 µg ml-1 aralığında bulundu ve korelasyon katsayısı 0,99'dan büyüktü. Yöntem kesinliği, %0.05 ile %0.61 arasındaki varyasyon katsayıları ile kabul edilebilir düzeydeydi. Ayrıca tablet numuneleri üzerinde yapılan geri kazanım çalışmaları sonucunda doğruluğun %99.45 ile %102.55 arasında tatmin edici sınırlar içinde olduğu görülmüştür. Ayrıca geliştirilen yöntemin yeşillik profili de yöntemin çevre dostu olduğunu göstermiştir.

Anahtar Kelimeler

• Analitik yeşillik değerlendirmesi
• HPLC
• kaptopril
• optimizasyon
• validasyon

GREEN PROCEDURE INDEX ASSESSMENT OF THE NOVEL STABILITY-INDICATING RP-HPLC METHOD FOR THE DETERMINATION OF CAPTOPRIL FROM PHARMACEUTICAL DOSAGE FORM

Öz

Objective: In this study, it was aimed to develop a novel reverse-phase liquid chromatography method for the ultra-sensitive determination of the antihypertensive drug captopril, using paracetamol, which is the common pain killer, as the internal standard. Optimization of all experimental conditions including composition of mobile phase, flow rate, and column temperature was carried out step by step, and the method validity of the developed method was examined according to international validation guidelines. Calibration range, linearity, the limit of determination, the limit of quantification, robustness, accuracy from commercial tablet samples, and method stability were examined in detail. In addition, the greenness profile for the developed method was assessed with the Green Analytical Procedure Index and Analytical Greenness Calculator techniques, which are frequently used in the literature. Material and Method: The chromatographic method was conducted with an XBridge C18 column (25 cm x 4.6 mm ID; 5 µm) packed with fully porous silica materials. All analyses were performed isocratically with a mobile phase containing acetonitrile:5 mM, pH 7.0 ammonium acetate solution (50:50, v/v) at a flow rate of 1.5 ml min-1. The injection volume was 5 μl, and the column was kept at 25°C in a column oven. The column eluate was monitored at 220 nm. Under optimized conditions, retention times of captopril, and paracetamol were approximately 1.59, and 2.0 min, respectively. Result and Discussion: This study described a fully validated, simple, sensitive, accurate, linear, precise, and reproducible reversed-phase liquid chromatography method for the determination of captopril in tablet samples. Under optimal experimental conditions, the linear range was found in the range of 0.5-200 µg ml-1 and the correlation coefficient was greater than 0.99. Method precision was acceptable, with coefficients of variation between 0.05% and 0.61%. In addition, as a result of the recovery studies carried out on the tablet samples, the accuracy was found to be within satisfactory limits between 99.45% and 102.55%. Moreover, the greenness profile of the developed method also showed that the method is environmentally friendly.

Anahtar Kelimeler

• Analytical greenness assessment
• captopril
• HPLC
• optimization
• validation

Kaynakça

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