title: Determination of a dipeptidyl peptidase IV agonist, β-aminoacyl containing thiazolidine derivatives (KR-66223) in rat plasma by liquid chromatography-tandem mass spectrometry.
abstract: 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 (LLE) 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 (10mM) (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 0.003-10μg/ml with a correlation coefficient (R(2)) greater than 0.99 and the lower limit of quantification was 3ng/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.
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon 305-600, Republic of Korea.
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Jong-Shik
authors.initials: JS
authors.lastname: Park
authors.forename: Su-Min
authors.initials: SM
authors.lastname: Jang
authors.forename: Byung Hoi
authors.initials: BH
authors.lastname: Lee
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Im-Sook
authors.initials: IS
authors.lastname: Song
authors.forename: Peter
authors.initials: P
authors.lastname: Silinski
authors.forename: Stephen Edward
authors.initials: SE
authors.lastname: Schneider
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000613:Aminobutyrates / Q000097:blood* / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D001798:Blood Proteins / Q000737:chemistry; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D018819:Dipeptidyl Peptidase 4 / Q000819:agonists*; D005561:Formates / Q000737:chemistry; D007099:Imipramine / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D053778:Thiazolidines / Q000097:blood / Q000737:chemistry*; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000097:Acetonitriles; D000613:Aminobutyrates; D001798:Blood Proteins; D005561:Formates; C561086:KR 66223; D053778:Thiazolidines; C030544:formic acid; D018819:Dipeptidyl Peptidase 4; D014633:Valine; D007099:Imipramine; C032159:acetonitrile