Green methods for the simultaneous analysis of pharmaceutical mixtures present in disparate concentration ranges: Application to antidiabetic mixtures

Abstract Diabetes-mellitus is one of the most common chronic diseases worldwide. Today, many single-pill combinations exist and are indicated especially for diabetic patients who are unable to achieve sufficient glycemic-control with one active component. However, some of these combinations are formulated in concentration ratios that present a real challenge for their analysis and quality-control assessment. For instant, linagliptin (L) and saxagliptin (S) are two oral dipeptidylpeptidase‐4 inhibitors that have recently been formulated with metformin (M) in a ratio of 1:400 with almost no simple analytical methods offered in literature for their analysis in such disparate concentration-ratio. In this study, a simple, fast and green capillary electrophoretic (CE) method was established for the simultaneous determination of L and S with M in pharmaceutical-dosage-forms. The developed method was linear in the range of 2–200 μg.mL−1 for L and S and 10–2000 μg.mL−1 for M with r > 0.9993 with low LOD and LOQ values that allowed the proposed method to be successfully applied for the sensitive determination of S, L and M in their binary-combinations of S-M and L-M in pharmaceutical-dosage-forms despite the large differences in M and L or S doses. Upon comparison with the few reported-methods, the proposed-method offers the advantages of high separation efficiency and low solvent consumption. In addition to using simple aqueous-buffer that adds to the greenness of the method and decrease the cost of operation. The Eco-scale penalty points approach and the Green Analytical Procedure Index were applied to assess the greenness of the developed method. Results revealed that the proposed method is a greener alternative to the reported ones This allows our proposed-method to be used for the routine high-through-put analysis required in quality-control laboratories as an efficient and simple eco- friendly analytical-tool.