Review on Method Development and Validation of Simultaneous Estimation of Aspirin and Clopidogrel by Reverse-Phase HighPerformance Liquid Chromatography (RP-HPLC)

A reliable, simultaneous Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC) method for quantifying aspirin (ASP) and clopidogrel (CLP) in combined dosage forms is central to the quality assurance of fixed-dose antiplatelet products.Both drugs are official in the Indian Pharmacopoeia, British Pharmacopoeia and United States Pharmacopeia-NF as single-component monographs.No compendial method currently exists for their joint estimation in a single tablet or capsule.This review consolidates and critically appraises the analytical methods reported over the last two decades for the concurrent determination of ASP and CLP by RP-HPLC, evaluating differences in stationary phase chemistry, mobilephase composition, detection wavelength, and validation performance (linearity, accuracy, precision, robustness, and stability-indicating capability) in accordance with ICH Q2(R1)/Q2(R2) guidelines.Reported methods predominantly employ C18 columns (Phenomenex, Luna, Inertsil, Gemini) with acetonitrile-methanol-phosphate buffer mobile phases at pH 2-4 and UV detection between 220 and 240 nm, achieving baseline resolution within 15 minutes.Comparative analysis identifies the method of Shrivastava et al. (2008) as the most extensively validated and reproducible protocol, while highlighting a persistent gap: no method has yet been formally validated exclusively for an ASP-CLP fixed-dose combination product rather than for the bulk drugs or related multi-drug regimens.The review concludes with recommendations for future stability-indicating, green-chemistry-compliant method development.