title: Liquid chromatographic-tandem mass spectrometry assay for quantitation of a novel antidiabetic S002-853 in rat plasma and its application to pharmacokinetic study.
abstract: A sensitive and selective LC-MS/MS method has been developed and validated for the estimation of novel antidiabetic synthetic flavonoid S002-853 in rat plasma using centchroman as an internal standard. The method involves a simple two-step liquid-liquid extraction with diethyl ether. The analyte was chromatographed on a Pierce Spheri-5, guard cyano column (30 x 4.6 mm i.d., 5 microm) with isocratic mobile phase consisting of methanol-ammonium acetate buffer (pH 4.6, 10 mm; 90 : 10, v/v) at a flow rate of 0.75 mL/min. The API 4000 triple-quadrupole LC-MS/MS system was operated under multiple reaction-monitoring mode. The ionization was performed by electrospray ionization technique in positive ion mode. The chromatographic run time was 6 min and the weighted (1/x(2)) calibration curves were linear over the range 0.78-400 ng/mL. The limit of detection and lower limit of quantification were 0.195 and 0.78 ng/mL, respectively. The intra- and inter-batch accuracy (%bias) and precision (%RSD) were found to be less than 8.47 and 11.6% respectively. The average absolute recoveries of S002-853 and internal standard from spiked plasma samples were >90%. S002-853 was stable for 8 h at ambient temperature, 4 weeks at -60 degrees C and after three freeze-thaw cycles. The assay was successfully applied to determine the pharmacokinetic parameters in male Sprague-Dawley rats after an oral dose administration at 25 mg/kg.
authors.affiliation: Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow, India.
authors.forename: N
authors.initials: N
authors.lastname: Gautam
authors.forename: R P
authors.initials: RP
authors.lastname: Singh
authors.forename: R
authors.initials: R
authors.lastname: Pratap
authors.forename: S K
authors.initials: SK
authors.lastname: Singh
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D007004:Hypoglycemic Agents / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007004:Hypoglycemic Agents