title: Enantioselective analysis of praziquantel and trans-4-hydroxypraziquantel in human plasma by chiral LC-MS/MS: Application to pharmacokinetics.
abstract: A simple enantioselective method for the determination of praziquantel (PZQ) and trans-4-hydroxypraziquantel (4-OHPZQ) in human plasma was developed and validated by high-performance liquid chromatography/mass spectrometry. The plasma samples were prepared by liquid-liquid extraction using a mixture of methyl-tert-butylether/dichloromethane (2:1, v/v) as extraction solvent. The direct resolution of PZQ and 4-OHPZQ enantiomers was performed on a Chiralpak AD column using hexane-isopropanol (75:25, v/v) as the mobile phase. Diazepam was used as internal standard. The method described here is simple and reproducible. The quantitation limit of 1.25ng/ml for each PZQ enantiomer and of 12.5ng/ml for each 4-OHPZQ enantiomer permits the use of the method in studies investigating the kinetic disposition of a single dose of 1.5g racemic PZQ. Enantioselectivity in the kinetic disposition of PZQ and 4-OHPZQ was observed in the clinical study, with the demonstration of a higher proportion of the (+)-(S)-PZQ and (-)-(R)-4-OHPZQ enantiomers in plasma.
authors: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors: Renata Monteiro
authors: RM
authors: Lima
authors: Maria Augusta Drago
authors: MA
authors: Ferreira
authors: Teresa Maria de Jesus
authors: TM
authors: Ponte
authors: Maria Paula
authors: MP
authors: Marques
authors: Osvaldo Massaiti
authors: OM
authors: Takayanagui
authors: Hector Hugo
authors: HH
authors: Garcia
authors: Eduardo Barbosa
authors: EB
authors: Coelho
authors: Pierina Sueli
authors: PS
authors: Bonato
authors: Vera Lucia
authors: VL
authors: Lanchote
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D016014:Linear Models; D011223:Praziquantel / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C067550:4-hydroxypraziquantel; D011223:Praziquantel