Stability indicating lc-ms/ms methods for direct acting antivirals used in hepatitis c therapy: a comprehensive review

Hepatitis C virus (HCV) infection continues to pose a significant global health burden, often leading to chronic liver diseases if inadequately treated. The introduction of direct acting antivirals (DAAs) such as Ledipasvir, Sofosbuvir, and Voxilaprevir has markedly improved therapeutic outcomes. With the growing clinical use of fixed dose combinations, the need for sensitive and stability indicating analytical methods has become increasingly important. This review critically evaluates reported analytical methods for the estimation of HCV DAAs, with a particular emphasis on stability indicating liquid chromatography-tandem mass spectrometry (LC-MS/MS) approaches. A comprehensive literature survey of peer reviewed articles and regulatory guidelines published between 2014 and 2023 was conducted. Reported UV, HPLC, and LC-MS/MS methods were systematically analyzed with respect to sensitivity, specificity, stability indicating capability, and regulatory compliance as per ICH guidelines. Conventional UV and HPLC methods were found to be suitable mainly for routine quality control but exhibited limited capability for degradation product detection. In contrast, LC-MS/MS methods demonstrated superior sensitivity, selectivity, and applicability for multi drug analysis and forced degradation studies. However, only a limited number of reports addressed comprehensive stability indicating analysis of all three DAAs within a single method. LC-MS/MS represents a robust and regulatory preferred analytical platform for the stability indicating evaluation of HCV DAAs. Further research focusing on comprehensive multi drug stability studies is warranted to support quality control and regulatory submissions.