Rapid and sensitive liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of yonkenafil and its major metabolites in rat plasma.
J Sep Sci
; 39(19): 3700-3708, 2016 Oct.
Article
em En
| MEDLINE
| ID: mdl-27601197
ABSTRACT
Yonkenafil is a promising drug for treatment of male erectile dysfunction. Previous studies showed that the piperazine-N,N'-deethylation metabolite, piperazine-N-deethylation metabolite, and piperazine-N-deethylation-N,N'-deethylation metabolite were the major metabolites of yonkenafil after extensive metabolism. We developed a sensitive and selective method for the simultaneous quantification of yonkenafil and its major metabolites using high-throughput liquid chromatography with tandem mass spectrometry. Analytes and internal standard were extracted from a small quantity of plasma (50 µL) using liquid-liquid extraction with diethyl ether/dichloromethane (6040, v/v), and the baseline separation was achieved on Zorbax SB-C18 column using ammonia/water/methanol (0.22080, v/v/v) as the mobile phase. The assay was performed with an electrospray positive ionization mass spectrometry through the multiple-reaction monitoring mode within 2 min. Calibration curve of the method was linear within the range of 1.00-1000 ng/mL for all the analytes with the intra- and interday precisions of 4.0-5.2 and 4.0-5.3% for yonkenafil, 3.1-4.9 and 3.1-5.2% for the piperazine-N,N'-deethylation metabolite, 4.8-6.8 and 4.8-7.3% for the piperazine-N-deethylation metabolite, and 2.9-6.1 and 5.4-6.3% for the piperazine-N-deethylation-N,N'-deethylation metabolite, respectively. The recoveries were above 90% with low matrix effects. The validated assay was successfully applied to support a preclinical pharmacokinetic study in six rats using a single oral dose of yonkenafil (8 mg/kg).
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MEDLINE
Assunto principal:
Pirimidinonas
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Pirróis
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Cromatografia Líquida de Alta Pressão
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Espectrometria de Massas em Tandem
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article