A Validated Reversed Phase‐High Performance Liquid Chromatographic Method for Simultaneous Estimation of Bisoprolol Fumarate, Cilnidipine, and Telmisartan With RGB12‐Based Sustainability Assessment

Abstract

The simultaneous estimation of multiple antihypertensive agents in fixed‐dose combination formulations requires robust and reliable analytical methods. A validated RP‐HPLC method for the simultaneous estimation of bisoprolol fumarate, cilnidipine, and telmisartan with robustness assessment using Box–Behnken Design is developed. Chromatographic separation was achieved using a Hypersil C 18 column (250 mm × 4.6 mm, 5 µm) with a mobile phase consisting of acetonitrile, 0.05 M potassium orthophosphate buffer, and methanol (45:20:35, v/v/v) at a flow rate of 1.0 mL/min and detection at 226.0 nm. The optimized method was validated in accordance with ICH Q2 (R2) guidelines for linearity, accuracy, precision, selectivity, specificity, and robustness. The developed method demonstrated excellent linearity with correlation coefficients ( R 2 ) greater than 0.995 over concentration ranges of 2.5–30 µg/mL for bisoprolol fumarate, 5–60 µg/mL for cilnidipine, and 20–240 µg/mL for telmisartan. Precision studies showed %RSD values below 2%, while recovery values ranged from 98% to 102%, confirming method accuracy. Robustness assessment and statistical analysis using Box–Behnken Design under deliberate variations indicated insignificant effects on analytical performance, demonstrating the reliability and consistency of the method. RP‐HPLC method was successfully developed and validated, providing a specific, precise, accurate, and robust analytical procedure for the simultaneous quantification of bisoprolol fumarate, cilnidipine, and telmisartan in combination. The method was found to align with principle of sustainable analytical chemistry as per the RGB12 evaluation, hence suitable for routine quality control and regulatory applications.