Enantioselective analysis of praziquantel and trans-4-hydroxypraziquantel in human plasma by chiral LC–MS/MS: Application to pharmacokinetics
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- 作者：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 ; Ve
- 关键词：Praziquantel ; Enantiomers ; Pharmacokinetics ; Metabolism
- 刊名：Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences
- 出版年：2009
- 出版时间：1 October 2009
- 年：2009
- 卷：877
- 期：27
- 页码：3083-3088
- 全文大小：404 K
文摘
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.