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

Author(s): Ran Meng, Danlu Zhang, Jianbo Ji, Lingyun Hu, Dequn Sun*, Haina Wang*

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 4 , 2019

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Graphical Abstract:


Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: P96, plasma, LC-MS/MS, pharmacokinetics, enantioselectivity, schistosomiasis.

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Article Details

Year: 2019
Published on: 19 March, 2019
Page: [379 - 387]
Pages: 9
DOI: 10.2174/1573412914666180608093636
Price: $65

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