QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE

Year 2024, Volume: 48 Issue: 3, 962 - 974, 10.09.2024

Vasudha Dadi , Saritha Medapati , Jagadeesh Kumar Baratam , Hemant Kumar Tatapudi , Gangu Naidu Challa , Srinivasa Rao Yarraguntla , Bhagavan Rajesh Babu Koppisetty

https://doi.org/10.33483/jfpau.1464923

Abstract

Objective: In this research, a validated RP-HPLC method for analyzing teriflunomide drug substance and its associated process-related impurities was developed with the assistance of the Quality by Design (QbD) approach.
Material and Method: The QbD methodology employs statistical design of experiments to establish a robust method within a defined "design space." This design space outlines the experimental parameters' range within which alterations will not significantly impact the results. Chromatographic separation was done on HPLC system connected to a PDA detector, and the column used was the C18 YmC-Triart with specifications of 125 cm x 4.0 mm x 5.0 μm. The optimized mobile phase consisted of 0.5% triethylamine buffer with pH 4.0 (± 0.05) and acetonitrile in a 65:35 v/v ratio, flow rate of 1.0 ml/min. Detection wavelength of 210 nm.
Result and Discussion: The developed RP-HPLC method successfully achieved high resolution, specificity, linearity, precision, accuracy, and robustness in quantifying both teriflunomide and its impurities simultaneously. Using a design of experiments (DoE) approach, critical method parameters were systematically identified and optimized, ensuring accurate and precise determination of impurity levels across the drug substance lifecycle. This validated method provides a thorough approach to ensuring the quality and safety of teriflunomide drug substances by delivering reliable data on impurity profiles. By applying Quality by Design (QbD) principles, not only does the method enhance understanding of the analytical process, but it also supports ongoing improvement and lifecycle management of the procedure.

Keywords

Method development, QbD, related impurities, RP-HPLC, teriflunomide

TERİFLUNOMİD VE İLAÇ MADDESİNİN ÜRETİMİNDEKİ SAFSIZLIKLARININ TAHMİNİ İÇİN TASARIMLA KALİTE DESTEKLİ RP-HPLC YÖNTEMİ

Abstract

Amaç: Bu araştırmada, teriflunomid ilaç maddesini ve onun süreçi ile ilişkili safsızlıkları Tasarımla Kalite (QbD) yaklaşımı yardımıyla analiz etmek için doğrulanmış bir RP-HPLC yöntemi geliştirildi.
Gereç ve Yöntem: QbD metodolojisi, tanımlanmış bir "tasarım alanı" dahilinde sağlam bir yöntem oluşturmak için deneylerin istatistiksel tasarımını kullanır. Bu tasarım alanı, değişikliklerin sonuçları önemli ölçüde etkilemeyeceği deneysel parametre aralığının ana hatlarını çizer. Kromatografik ayırma, bir PDA detektörüne bağlı bir HPLC sistemi üzerinde gerçekleştirildi ve kullanılan kolon, 125 cm x 4.0 mm x 5.0 μm spesifikasyonlarına sahip C18 YmC-Triart'tı. Optimize edilmiş mobil faz, pH 4.0 (± 0.05) olan %0.5 trietilamin tamponundan ve 65:35 v/v oranında, 1.0 ml/dak akış hızında asetonitrilden oluşuyordu. 210 nm algılama dalga boyu.
Sonuç ve Tartışma: Geliştirilen RP-HPLC yöntemi, hem teriflunomidin hem de onun safsızlıklarının aynı anda ölçülmesinde yüksek çözünürlük, özgüllük, doğrusallık, kesinlik, doğruluk ve sağlamlığı başarıyla elde etti. Bir deney tasarımı (DoE) yaklaşımı kullanılarak, kritik yöntem parametreleri sistematik olarak tanımlandı ve optimize edildi; böylece ilaç maddesi yaşam döngüsü boyunca safsızlık seviyelerinin doğru ve kesin olarak belirlenmesi sağlandı. Doğrulanmış bu yöntem, safsızlık profilleri hakkında güvenilir veriler sunarak teriflunomid ilaç maddelerinin kalitesini ve güvenliğini sağlamaya yönelik kapsamlı bir yaklaşım sağlar. Tasarımla Kalite (QbD) ilkelerini uygulayarak, yöntem yalnızca analitik sürecin anlaşılmasını geliştirmekle kalmaz, aynı zamanda prosedürün sürekli iyileştirilmesini ve yaşam döngüsü yönetimini de destekler.

Keywords

İlgili safsızlıklar, QbD, RP-HPLC, teriflunomid, yöntem geliştirme

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