Enantioselective Plasma Pharmacokinetic Study of a Novel Anti- Sichistosomiasis Agent P96 in Rat by Liquid Chromatography-tandem Mass Spectrometry

2-Cyclopentanecarbonyl-1,2,3,6,7,11b-hexahydro-pyrazino[2,1- a]isoquinolin- 4-one (P96), was found to be a novel drug candidate with one chiral center to treat schistosomiasis caused by Schistosoma japonicum. Objective: To study pharmacokinetic characteristics, a simple, rapid and sensitive liquid chromatography- tandem mass spectrometry (LC-MS/MS) method was developed and fully validated for the quantification analysis of P96 in rat plasma. Chromatographic separation was performed on a C18 column with gradient eluted mobile phase composed of acetonitrile and water at a flow rate of 0.5 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using positive mode electrospray ionization in the multiple reactions monitoring (MRM) mode. Excellent linearity was observed in the range of 3-900 ng/mL with the lower limit of quantification of 3 ng/mL in rat plasma for P96. The intra- and inter-day precisions exhibited less than 6.6%. Mean recoveries ranged from 96.9% to 102.4%. This method was applied to investigate the enantioselective differences on the pharmacokinetics between (R,S)-P96 and its enantiomers in rats after oral administration. The enantioselective differences of (R)-P96, (S)-P96 and (R,S)-P96 were found and compared. The established method was found to be accurate, precise, and sensitive and can be applied to investigate the stereoselective differences on pharmacokinetics between rac-P96 and its enantiomers.

• Publication year

  2019

• Venue

  Current Pharmaceutical Analysis

• Publication date

  2019-05-31

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.2174/1573412914666180608093636
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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