PHARMASPIRE - Volume 10, Issue 3, July - September, 2018
Pages: 113-120
Date of Publication: 14-Jun-2022
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Effect of metformin and pioglitazone on serum albumin binding of selected sulfonylureas
Author: Navjot Kaur Sandhu, Sukhbir Kaur, Durga Das Anghore, Pawan Kumar Porwal
Category: Pharmaceutics
Abstract:
Metformin (MET) and pioglitazone (PIO) are known to induce conformation changes in the tertiary structure of human serum albumin and inhibit the non-enzymatic glycation of albumin. The pharmacological doses of sulfonylureas are about 100–500 time less as compared to MET and about 10–20 time less than PIO. The liquid chromatography coupled with tandem mass spectrometry was used to quantify all analytes. The retention of all analytes was made on a C8 column (50 mm × 2.1 mm and 2.5 µm) using 10 mM ammonium acetate buffer in gradient elution with acetonitrile at 0.25 ml/min flow rate and quantitated at selective reaction monitoring mode for the respective analyte. The Amicon® ultrafiltration device was used to access albumin binding studies. The analytes were spiked to 4% recombinant human serum albumin (rHSA) and 10% glycated human serum albumin (Gly-HSA) corresponding to their peak plasma concentration. Finally, the rHSA and Gly-HSA were incubated with various levels of MET, PIO, and sulfonylurea/s. The optimized bioanalytical liquid chromatography–tandem mass spectrometry was found linear in the range of 5–2000 ng/mL for MET and PIO, whereas, the calibration curve for glibenclamide and glimepiride was made in the range of 5–500 ng/mL. The lower limit of quantitation (LLOQ) for glibenclamide and glimepiride was 0.25 ng/mL, and LLOQ values for MET and PIO were 0.50 ng/mL and 1.0 ng/mL, respectively, with sufficient accuracy and precision. Competitive inhibition of non-enzymatic glycation of rHSA was observed in the presence of MET and PIO. An alteration of protein binding capacity was observed for sulfonylurea when incubated with glucose plus MET plus and PIO in comparison to control.
Keywords: Albumin, liquid chromatography–tandem mass spectrometry, metformin, pioglitazone, protein binding, sulfonylurea
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