Rapid Stability Indicating HPLC Method for the Analysis of Leflunomide and Its Related Impurities in Bulk Drug and Formulations

Abstract

Leflunomid (LFNM), izoksazol türevine ait ve immüne süpresif ve antienflamatuvar aktiviteye sahip bir ilaçtır. Literatür taraması, farmasötik dozaj formlarında ve bulk ilaçlarda LFNM ve ilgili safsızlık A ve B'nin değerlendirilmesi için rapor edilen bir yöntemin olmadığını doğrulamaktadır. Bu nedenle bu çalışma, LFNM'nin ve A ve B safsızlıklarının ayrıştırılması ve miktarının belirlenmesi için hızlı stabilite göstergeli RP-YBSK yöntemini geliştirmeyi amaçlamıştır. Gereç ve Yöntemler: LFNM ve ilgili safsızlık A ve B'nin eş zamanlı analizi için mobil faz oranı, pH, akış hızı, stasyoner faz ve detector dalga boyu gibi metod koşullarının sistematik testleri gerçekleştirilmiştir. Geliştirilen yöntem farklı stress koşullarında zoraki bozunma çalışmalarını içeren ICH yönergelerine göre valide edilmiştir. Bulgular: Optimal ayrıştırma, Thermo Scientific Hypersil ODS C18 kolonu (250 mm×4,6 mm; 5 µm id) üzerinde, 40:30:30 (h/h) oranında asetonitril, methanol ve 0,1 M sodium perklorat bileşiminden oluşan mobil faz kullanılarak elde edilmiştir; izokratik elüsyonda 1,0 mL/dak akış hızında pH 4,6 idi. UV saptaması 246 nm dalga boyunda gerçekleştirilmiştir. İyi-kararlı pikler, çok sayıda teorik plaka, daha az kuyruklama faktörü ve tekrarlanabilir göreceli retansiyon süresi ve tepki faktörü ile elde edilmiştir. Yöntem valide edilmiştir ve tüm validasyon parametreleri kabul limitinde bulunmuştur. Stabilite testleri, analit çözeltisinin beş farklı stress koşuluna, yani 1 N HCl, 1 N NaOH, %3 H 2 O 2 , tozun termal degradasyonuna ve UV radyasyonuna Objectives: Leflunomide (LFNM) is a drug that belongs to isoxazole derivatives and has immunosuppressive and anti-inflammatory activities. A literature search confirms that there is no method reported for the simultaneous estimation of LFNM and its related impurities A and B in pharmaceutical dosage forms or in bulk drug. Hence the present work aimed to develop a simple stability indicating RP-HPLC method for the separation and quantification of LFNM and its impurities A and B. Materials and Methods: Systematic trials of method conditions like mobile phase ratio, pH, flow rate, stationary phase, and detector wavelength were performed for the simultaneous analysis of LFNM and its related impurities A and B. The developed method was validated as per the ICH guidelines including forced degradation studies in different stress conditions. Results: Optimized separation was achieved on a Thermo Scientific Hypersil ODS C18 column (250 mm×4.6 mm; 5 µm id) using mobile phase composition of acetonitrile, methanol, and 0.1 M sodium perchlorate in the ratio of 40:30:30 (v/v), pH 4.6, at a flow rate of 1.0 mL/min in isocratic elution. UV detection was carried out at a wavelength of 246 nm. Well-resolved peaks were observed with high numbers of theoretical plates, lower tailing factor, and reproducible relative retention time and response factor. The method was validated and all the validation parameters were found to be within the acceptance limits. Stability tests were done through exposure of the anal...

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