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

作者：Kim Min Sun; Park Jong Shik; Jang Su Min; Lee Byung Hoi; Ahn Sung Hoon; Ahn Jin Hee; Yoo Sung Eun; Song Im Sook; Silinski Peter; Schneider Stephen Edward; Bae Myung Ae^*

来源：Journal of Pharmaceutical and Biomedical Analysis, 2011, 55(5): 1083-1088.

DOI：10.1016/j.jpba.2011.03.015

• KR-66223
• Method validation
• Pharmacokinetics
• LC/MS/MS
• Rat plasma

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.

• 出版日期2011-7-15