Quantitative determination of omapatrilat and its metabolites in human plasma by HPLC coupled with tandem mass spectrometry.
OBJECTIVE
To develop a sensitive and specific analytical method for the quantitative determination of omapatrilat (BMS-186716) and its metabolites (BMS-196087, 225308, 198433, and 253653) in human plasma.


METHODS
Methyl acrylate (MA) was selected to react with BMS-186716, 196087, and 253653 to protect the free sulfhydryl groups. High pressure liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to detect the analytes.


RESULTS
The method was validated over the concentration range of 0.2-250 microg/L for BMS-186716, 0.5-250 microg/L for BMS-196087, 1-250 microg/L for BMS-225308, 2-250 microg/L for BMS-198433, and 10-2500 microg/L for BMS-253653. The limit of quantitation was in turn 0.2, 0.5, 1, 2, and 10 microg/L, respectively. The extraction recovery was on average 60.5 %, 88.6 %, 76.3 %, 71.2 %, and 26.6 %, respectively. Inter- and intra-day precision of quality control samples (QC) was all within 15 % and accuracy was within 85 %--115 %. The analytes in human plasma were found to be stable after three cycles of freeze-thaw and for at least 6 h at room temperature (25 oC). No significant change was found in reconstituted reagent after 24 h at room temperature and results of long-term stability showed all the analytes in human plasma were stable for at least 3 months at -30 oC freezing condition.


CONCLUSIONS
This method is rapid, sensitive and specific for the pharmacokinetics study of omapatrilat and its metabolites.
Wang
Hong-Yun
HY
Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences, Beijing 100730, China. wanghongyunpumc@sohu.com
Hu
Yu-Fang
YF
Jiang
Ji
J
Hu
Pei
P
D002317:Cardiovascular Agents / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D013058:Mass Spectrometry; D011725:Pyridines / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D013841:Thiazepines / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics
D002317:Cardiovascular Agents; D011725:Pyridines; D013841:Thiazepines; C106266:omapatrilat