Eco-friendly UPLC and spectrophotometric methods for simultaneous estimation of ternary mixture metoprolol, chlorthalidone and telmisartan

Abstract

The proposed work aims to develop and optimize accurate, precise, and reproducible UPLC and Double Divisor Ratio Spectra Derivative Spectrophotometric (DDRS-DS) methods for the selective quantification of a three-component antihypertensive drug combination comprising metoprolol succinate, chlorthalidone and telmisartan. The UPLC method utilized a mobile phase consisting of acetonitrile: phosphate buffer (pH 4) in a ratio of 60:40 (v/v), with Agilent® Poroshell C18 column (150 mm × 3 mm, 1.9 μm) as the stationary phase maintained at 30°C. The flow rate was 0.3 mL/min, while UV detection was monitored at 215.0 nm. Regarding UPLC method, linearity was established over the concentration ranges of 2.0–60.0, 0.7–50.0, and 2.0–60.0 μg/ mL for metoprolol, chlorthalidone, and telmisartan, respectively, whereas for DDRS-DS method, the corresponding ranges were 2.0–20.0, 1.0–12.0, and 2.0–20.0 μg/mL, respectively. The eco-friendliness of the developed methods was evaluated using AES, NEMI, GAPI, and AGREE, achieving AES scores of 92 and 97, and AGREE scores of 0.77 and 0.84, for the UPLC and DDRS-DS methods, respectively. Validation of the developed methods was carried out according to ICH guidelines and demonstrated environmental friendliness, selectivity, and sensitivity for the quantification of the cited analytes in raw material and pharmaceutical preparations.