Merging green chemistry with spectrophotometry: Univariate vs. multivariate assessment of a novel triple antihypertensive combination, amlodipine, telmisartan, and indapamide

A smart, accurate, and eco-friendly spectrophotometric platform was designed for the concurrent determination of amlodipine besylate (AML), indapamide (IND), and telmisartan (TEL) in their combined pharmaceutical formulations. These antihypertensive agents are frequently co-administered due to their complementary mechanisms of action: AML, a calcium channel blocker, induces vasodilation; IND, a thiazide-like diuretic, promotes natriuresis and reduces plasma volume; while TEL, an angiotensin II receptor blocker (ARB), inhibits vasoconstriction and aldosterone secretion. The combination offers a synergistic effect in managing essential hypertension, especially in patients requiring multidrug therapy. Two well-established spectrophotometric platforms, Fourier self-deconvolution (FSD) and Third derivative (D1), are introduced to resolve and accurately quantify a captivating tertiary mixture effectively. These methods were developed for simultaneous determination of the three drugs over a concentration range of 2–40 μg/mL for AML, 2–20 μg/mL for IND, and 2–45 μg/mL for TELIn addition to the univariate approaches, two multivariate chemometric models—Partial Least Squares (PLS) and Principal Component Regression (PCR)—were successfully constructed for the concurrent estimation of the studied drugs. The predictive capabilities of these models were confirmed, showing root mean square error of prediction (RMSEP) values within the range of 0.0749 to 0.4535, indicating high model accuracy. The selectivity of the proposed spectrophotometric and chemometric methods was verified through the analysis of laboratory-prepared mixtures containing varying ratios of the investigated drugs, as well as their commercial dosage form. To ensure environmental compliance, the greenness profile of the developed procedures was evaluated using multiple assessment tools, including the spider diagram and the Modified Green Analytical Procedure Index (MoGAPI), both of which confirmed the eco-friendly nature of the methods. The proposed techniques were validated in accordance with the International Council for Harmonisation (ICH) guidelines to confirm their reliability. Furthermore, the accuracy of the developed methods was assessed using the standard addition technique. Statistical comparison of the obtained results with those from reported HPLC methods revealed no significant difference in accuracy or precision at a confidence level of p = 0.05, confirming the equivalency and robustness of the proposed procedures. • The study introduces the first spectrophotometric methods for the simultaneous quantification of Amlodipine, Telmisartan, and Indapamide in a combined dosage form. • The developed methods integrate principles of Green Analytical Chemistry (GAC) with smart chemometric techniques (PLS and PCR). • The univariate and multivariate models were optimized and validated, offering excellent accuracy and precision even in the presence of interfering species. • The proposed approach eliminates the need for hazardous organic solvents, minimizing environmental impact and analytical waste. • The study provides a sustainable and cost-effective analytical alternative to traditional chromatographic methods. • The work contributes to the field of sustainable analytical chemistry and aligns with the mission of the journal Sustainable Chemistry and Pharmacy.