Development of an ecofriendly thin-layer chromatography‒densitometry method for the simultaneous quantification of dapagliflozin propanediol monohydrate, sitagliptin, and metformin hydrochoride in tablet formulation using analytical ecoscale, GAPI, and AGREE tools

Abstract

In recent years, green analytical chemistry (GAC) has played an important role in the development of environmentally friendly analytical methods. In the field of pharmaceutical analysis, ecofriendly analytical methods are attracting attention to ensure the safety of workers and the environment. A three-drug combination of metformin hydrochloride, sitagliptin, and dapagliflozin propanediol monohydrate was recently approved for the treatment of type II diabetes. A simple, rapid, and reproducible green thin-layer chromatography (TLC) method was developed for the simultaneous determination of metformin hydrochloride, sitagliptin, and dapagliflozin propanediol monohydrate in tablet dosage form. Chromatographic separation was carried out on precoated TLC silica gel 60F₂₅₄, using the mobile phase consisting of ethyl acetate‒acetic acid‒water (6:2:1.5, V/V). The separated bands were quantified by scanning at a detection wavelength of 205 nm. The three drugs were properly resolved (R_F values of metformin hydrochloride: 0.25 ± 0.02, sitagliptin: 0.62 ± 0.03, and dapagliflozin propanediol monohydrate: 0.86 ± 0.02) using these chromatographic conditions. The method was validated in terms of linearity, accuracy, precision, specificity, limit of detection (LOD), and limit of quantification (LOQ) in accordance with the International Council for Harmonisation (ICH) Q2(R1) guidelines. The calibration curves were found to be linear over the ranges of 5‒17.5 µg/band for metformin hydrochloride, 1‒3.5 µg/band for sitagliptin and 0.1‒0.35 µg/band for dapagliflozin propanediol monohydrate. Greenness assessment of the developed method was evaluated using three different assessment tools, viz., analytical ecoscale, green analytical procedure index (GAPI), and analytical greenness (AGREE). This is the first analytical method to be developed for the simultaneous estimation of these drugs in pharmaceutical dosage form. The developed method was applied for the simultaneous estimation of metformin hydrochloride, sitagliptin, and dapagliflozin propanediol monohydrate in tablet dosage form.