LC-MS determination and pharmacokinetic study of a novel sulfonylurea: Potential hypoglycemic agent in rat plasma

To support preclinical pharmacokinetic investigation of 1-[4-[2-(4-bromobenzene-sulfonaminoethyl)phenylsufonyl]-3-(trans-4- methylcyclohexyl)urea (G004), a rapid, sensitive and specific high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed and validated. Glibenclamide was employed as internal standard. After liquid-liquid extraction the analyte was analyzed on a Kromasil C₁₈ column (150 × 2.0 mm i.d.) with a mobile phase consisted of acetonitrile-water (0.05% acetic acid), 30:70 (v/v). The flow rate was 0.2 mL min^-1. Detection was performed on a quadrupole mass spectrometer using an electrospray ionization interface and the selected-ion monitoring (SIM) mode. The retention time was about 3.5 and 4.2 min for Glibenclamide and G004, respectively. The assay was linear over the concentration range of 2.0-500.0 ng mL^-1. Extraction Recovery of G004 in rat plasma was more than 87%. The intra- and inter-assay precision was lower than 11.5% (CV). This validated method was successfully applied to the pharmacokinetics of G004 in rats.