A new rapid and economic liquid chromatographic method for simultaneous determination of meglitinides with metformin: application in the presence of metformin and repaglinide impurities and related compounds

摘要

A new liquid chromatographic method was developed for simultaneous determination of the widely used oral antidiabetic, metformin hydrochloride with antidiabetics comprising the meglitinides class in bulk, laboratory-prepared mixtures and pharmaceutical products. It was applied in the presence of metformin-reported impurity (1-cyanoguanidine). It was also applied for the determination of repaglinide in the presence of its related compounds. Chromatographic separation was achieved with isocratic elution mode using a mobile phase of acetonitrile: 0.01 M sodium dihydrogen phosphate (pH: 2.8) (67:33; v/v) flowing through a LiChrospher NH2 (amino) Agilent(A (R)) column (250 x 4.6 mm-5 A mu m) at a rate of 0.8 mL/min at ambient temperature in a run time of 4 min. UV detection was carried out at 220 nm. The method was validated according to International Conference on Harmonization guidelines. Linearity, accuracy and precision were satisfactory over concentration ranges (A mu g/mL): 3.5-350 for metformin hydrochloride, 14-140 for nateglinide, 1-100 for mitiglinide calcium and 0.1-100 for repaglinide. Coefficients of determination were E integral 0.99 for all analytes. Limits of quantification were found (in A mu g/mL): 0.06, 0.08, 0.198 and 0.029 for metformin hydrochloride, nateglinide, mitiglinide calcium and repaglinide, respectively. The present method was found to be rapid, selective, economic and simple in operation satisfying the chromatographers' needs for quality assessment of pharmaceutical products.