Determination of a dipeptidyl peptidase IV agonist, β-aminoacyl containing thiazolidine derivatives (KR-66223) in rat plasma by liquid chromatography-tandem mass spectrometry

초록

A sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for a novel dipeptidyl peptidase IV agonist (DDP-IV) agonist, KR-66223, in rat plasma. It involves liquid-liquid extraction (LIE) followed by HPLC separation and electrospray ionization tandem mass spectrometry. KR-66223 and imipramine (IS) was separated on Gemini-NX C18 column with mixture of acetonitrile-ammonium formate (10 mM) (90:10, v/v) as mobile phase. The ion transitions monitored were m/z 553.2 -> 206.2 for KR-66223, m/z 281.3 -> 86.1 for imipramine in multiple reaction monitoring (MRM) mode. The linear ranges of the assay were 0.003-10 mu g/ml with a correlation coefficient (R(2)) greater than 0.99 and the lower limit of quantification was 3 ng/ml. The average recovery was 78.9% and 87.1% from rat plasma for KR-66223 and imipramine, respectively. The coefficients of variation of intra- and inter-assay were 3.9-14.4% and the relative error was 0.8-11.5%. The method was validated and successfully applied to the pharmacokinetic study of KR-66223 in rat. (C) 2011 Elsevier B.V. All rights reserved.

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