Validation of a LC/MS/MS method for the quantitation of a new gastroprokinetic agent SHR116958 and its metabolite in rat plasma.
A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was succesfully developed for the simultaneous determination of SHR116958 (a new gastroprokinetic agent) and its metabolite in rat plasma under the condition that tamsulosin was used as the internal standard. The analytes and internal standard were extracted by liquid-liquid extraction (LLE). After electrospray ionization, positive ion fragments were detected in the multiple reaction monitoring (MRM) mode with a triple quadrupole tandem mass spectrometer. The method was linear in the concentration range of 2.71-5560 ng x mL(-1) with an average correlation > 0.99 for both SHR116958 and its metabolite. Moreover, the method was validated according to FDA guidance in terms of accuracy and precision, in the meanwhile stability of compounds was well established in a battery of studies, i.e., bench-top, autosampler and long-term storage stability as well as freeze/thaw cycles. Therefore, the method proved to be suitable for pharmacokinetics study of SHR116958 and its metabolite in rat.
Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.
Xin
X
Li
Lina
L
Du
Chenyun
C
Wang
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics*; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D007553:Isotope Labeling; D009025:Morpholines / Q000493:pharmacokinetics*; D011786:Quality Control; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization
D001549:Benzamides; D005765:Gastrointestinal Agents; D007202:Indicators and Reagents; D009025:Morpholines; C569379:SHR116958; D012996:Solutions