Ecological HPLC method for analyzing an antidiabetic drug in real rat plasma samples and studying the effects of concurrently administered fenugreek extract on its pharmacokinetics

Abstract

Currently, the total number of diabetic people worldwide is constantly increasing. Metformin (MET) is known to be a first-line antidiabetic drug with varied, wide-reaching applications. Concurrent administration of phytomedicines such as fenugreek extract with synthetic drugs is very common. It is reported that concomitant administration of fenugreek extract with metformin maintains lower blood glucose levels than metformin alone. In this work, an ecofriendly RP-HPLC method was established to study and compare the pharmacokinetics of metformin with and without the contemporary administration of fenugreek extract using rat as an animal model. In the developed method, a solvent mixture of 0.5 mM KH2PO4 solution : methanol (65 : 35, v/v) was used as a mobile phase and guaiphenesin was used as an internal standard. The plasma concentration-time curve was plotted, and non-compartmental pharmacokinetic analysis was performed using PKSolver. The results of the pharmacokinetic study showed that concurrent administration of fenugreek significantly increased the bioavailability of metformin and doubled the time required to reach the peak plasma concentration (T max). Moreover, the volume of drug distribution decreased by about 70%, while its rate of clearance decreased by about 55.96%. Accordingly, the administration of fenugreek in combination with metformin significantly affected the pharmacokinetics of metformin, and this combination will be very useful in controlling blood glucose levels in diabetic patients. The greenness of the method was assessed using the Analytical Eco-Scale, Analytical Method Volume Intensity (AMVI), and National Environmental Method Index (NEMI), and all results affirmed that the method can be considered to be ecological.

Conflict of interest statement

Authors declare that they have no conflict of interest.

This journal is © The Royal Society of Chemistry.

Figures

Fig. 1. HPLC chromatograms of (A) blank plasma, (B) plasma spiked with 15 μg mL−1 metformin and 50 μg mL−1 guaiphenesin, and (C) a rat plasma sample after 2 hours (from group III) spiked with 50 μg mL−1 guaiphenesin.

Fig. 2. Mean plasma concentration–time curves of metformin after oral administration of 300 mg kg−1 metformin (A) and after oral administration of 300 mg kg−1 metformin + 500 mg kg−1 fenugreek extract.

Fig. 3. The NEMI pictogram of the developed RP-HPLC method.