Development of liquid chromatographic method for the simultaneous determination of metformin and miglitol in human plasma: application to pharmacokinetic studies

摘要

The purpose of the present study was to establish a simple, fast, and sensitive method for the simultaneous estimation of metformin (MET) and miglitol (MIG) by LC/MS method in human plasma. Chromatographic separation of metformin and miglitol was accomplished by a Zorbax Eclipse C-18 analytical column using voglibose as an internal standard. The mobile phase consisting of 95 % ammonium acetate and 5 % methanol was pumped isocratically at a flow rate of 0.5 mL/min. The eluted analytes were monitored by mass detector in positive ion mode. The developed method has been validated by evaluating all of the parameters specified according to the US Food and Drug Administration's bioanalytical validation method guidelines. The calibration curve showed a good correlation coefficient during the linearity study in the range of 20-2000 ng/mL for MET and 25-4000 ng/mL for MIG. The accuracy of the proposed method for analysis of MET and MIG was 98.18 and 99.13 %, respectively. Furthermore, both inter-day and intra-day analyses showed less than 7 % of the relative standard deviation. In addition, recovery of MET and MIG from plasma was found to be 94.7 and 93.1 %, respectively. Subsequently, the method was applied to determine the pharmacokinetic parameters such as T (max), C (max), AUC(0-t), T (1/2), and Kel for both the drugs in plasma. The developed LC-MS method has been successfully used for the simultaneous determination of MET and MIG and applied for pharmacokinetic studies. Hence, this method is demonstrated to be appropriate for clinical monitoring of metformin and miglitol.