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Enantioselective analysis of praziquantel and trans-4-hydroxypraziquantel in human plasma by chiral LC–MS/MS: Application to pharmacokinetics

2009; Elsevier BV; Volume: 877; Issue: 27 Linguagem: Inglês

10.1016/j.jchromb.2009.07.036

1873-376X

Renata Monteiro Lima, Maria Augusta Drago Ferreira, Teresa Maria de Jesus Ponte, Maria Paula Marques, Osvaldo Massaiti Takayanagui, Hector Hugo Garcia, Eduardo Barbosa Coelho, Pierina Sueli Bonato, Vera Lúcia Lanchote,

Microfluidic and Capillary Electrophoresis Applications

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 1.25 ng/ml for each PZQ enantiomer and of 12.5 ng/ml for each 4-OHPZQ enantiomer permits the use of the method in studies investigating the kinetic disposition of a single dose of 1.5 g 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.