Determination of a peroxisome proliferator-activated receptor γ agonist, 1-(trans-methylimino-N-oxy)-6-(2-morpholinoethoxy-3-phenyl-1H-indene-2-carboxylic acid ethyl ester (KR-62980) in rat plasma by liquid chromatography-tandem mass spectrometry.
A novel peroxisome proliferator-activated receptor γ (PPARγ) agonist, KR-62980, was determined by liquid-liquid extraction with ethyl acetate and liquid chromatography-tandem mass spectrometry (LC/MS/MS) in rat plasma. In order to evaluate the pharmacokinetics of KR-62980, a reliable, selective and sensitive high-performance liquid chromatographic method with electrospray ionization tandem mass spectrometry was developed for the quantification of KR-62980 in rat plasma. KR-62980 and imipramine (IS) were separated on Hypersil GOLD C18 column with a mixture of acetonitrile-ammonium formate (10mM) (80:20, v/v) as mobile phase. The ion transitions monitored were m/z 437.2 → 114.2 for KR-62980, m/z 281.3 → 86.1 for imipramine in multiple reaction monitoring (MRM) mode. The percent recoveries of KR-62980 and imipramine were 90.1 and 98.4% from rat plasma, respectively. The linear dynamic range extended from 0.01 to 10 μg/ml with a correlation coefficient (R(2)) greater than 0.99 and the lower limit of quantification was 0.01 μg/ml. The mean of intra- and inter-assay precisions was 2.1 and 9.3%. The method was validated and successfully applied to the pharmacokinetic study of KR-62980 in rat.
Kim
Min-Sun
MS
Drug Discovery Platform Technology Team, Medicinal Science Division, Korea Research Institute of Chemical Technology, Daejon 305-600, Republic of Korea.
Song
Jin Sook
JS
Roh
Hyeongjin
H
Park
Jong-Shik
JS
Ahn
Jin Hee
JH
Ahn
Sung-Hoon
SH
Bae
Myung Ae
MA
D000097:Acetonitriles / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D002623:Chemistry Techniques, Analytical; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D005561:Formates / Q000737:chemistry; D007192:Indenes / Q000032:analysis* / Q000097:blood / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D008956:Models, Chemical; D009025:Morpholines / Q000032:analysis* / Q000097:blood / Q000737:chemistry; D047495:PPAR gamma / Q000819:agonists*; D011786:Quality Control; D051381:Rats; D015203:Reproducibility of Results
C513115:1-(methylimino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-1H-indene-2-carboxylic acid ethyl ester; D000097:Acetonitriles; D005561:Formates; D007192:Indenes; D009025:Morpholines; D047495:PPAR gamma; C030544:formic acid; C032159:acetonitrile