title: A quantification method for determination of racemate praziquantel and R-enantiomer in rat plasma for comparison of their pharmacokinetics.
abstract: 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-C18 column. An entire run time for chromatographic separation was no more than 5min. The present method for analytes manifested that high sensitivity (the lower limit of quantification was 3.0ng/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 R-enantiomer as a replacement of racemate praziquantel for treatment of schistosomiasis.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Danlu
authors.initials: D
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Haina
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ji
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, Jinan, China. Electronic address: nielei2004@sdu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Nie
authors.affiliation: Marine College, Shandong University at Weihai, Weihai, China. Electronic address: dequn.sun@sdu.edu.cn.
authors.forename: Dequn
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000032:analysis / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods*; D057230:Limit of Detection; D008297:Male; D011223:Praziquantel / Q000032:analysis / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D012552:Schistosomiasis / Q000188:drug therapy; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods*
chemical_list: D000871:Anthelmintics; D011223:Praziquantel
keywords: Liquid chromatography; Pharmacokinetics; R-enantiomer; Racemate praziquantel; Tandem mass spectrometry