A quantification method for determination of racemate praziquantel and R-enantiomer in rat plasma for comparison of their pharmacokinetics

Praziquantel is the drug of first choice for the control and treatment of all forms of,schistosomiasis. Praziquantel is administered as a racemate, including R-enantiomer and S-enantiomer. Among them, R-enantiomer has main contribution to schistosomicidal activity. In this study, a sensitive and rapid liquid chromatography with tandem mass spectrometry was established and validated to determine the concentration of racemate praziquantel and R-enantiomer in rat plasma after oral administration. Chromatographic separation was performed on an Agilent Zorbax SB-Cl8 column. An entire run time for chromatographic separation was no more than 5 min. The present method for analytes manifested that high sensitivity (the lower limit of quantification was 3.0 ng/mL), satisfactory accuracy (relative error <=+/- 15%) and precision (relative standard deviation <= 15%) were achieved. There was no obvious matrix effect found. The average recoveries of racemate praziquantel and R-enantiomer were both above 85%. Then, the developed method had a successful application to comparative pharmacokinetic study of racemate praziquantel and R-enantiomer. Meanwhile, the differences in their pharmacokinetic parameters were compared and analyzed. The present quantification method and comparative pharmacokinetic study would provide a useful reference for the drug development of enantiopure schistosomicidal Renantiomer as a replacement of racemate praziquantel for treatment of schistosomiasis. (c)2017 Elsevier B.V. All rights reserved.