LC-MS/MS Assay for Quantification of a Novel Antidiabetic Flavone Derivative S002-857 in Rat Plasma, Urine and Feces: Application in Pharmacokinetic Studies

Abstract

This study aimed to develop an LC-MS/MS assay for the quantitation of S002-857 in plasma, urine and feces to evaluate the pharmacokinetic parameters and elimination pathway for further development of S002-857. A sensitive and selective LC-MS/MS method was developed and validated for estimating a novel antidiabetic flavone derivative, S002-857, synthesized by Central Drug Research Institute, CSIR, Lucknow, India. Plasma and urine samples were prepared by two-step liquid-liquid extraction with diethyl ether and feces by protein precipitation using acetonitrile. The analyte was chromatographed on a cyano column with methanol-ammonium acetate buffer (pH 4.6, 10 mM; 90:10, v/v). The calibration curves were linear over a range of 0.78-400 ng mL -1 for plasma and 1.56-400 ng mL -1 for urine and feces samples. The accuracy and precision were \15% for plasma, urine and feces samples. The recoveries from spiked plasma, urine and feces samples were [85%. S002-857 was stable in plasma for 8 h at ambient temperature, 30 days at -60°C and after three freeze-thaw cycles. The assay was successfully applied to determine the pharmacokinetic parameters and excretion profile in male rats.

Flavone-Based Novel Antidiabetic and Antidyslipidemic Agents

“…The pharmacokinetic parameters were evaluated from plasma concentration–time profile in Sprague–Dawley male rats (Table ) . After oral dose administration of compounds 70 , 70a , and 90a , the elimination half-lives ( t 1/2 ) were found to be 19.56, 19.83, and 3.97 h, respectively.…”