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 mu L) using liquid-liquid extraction with diethyl ether/dichloromethane (60:40, v/v), and the baseline separation was achieved on Zorbax SB-C-18 column using ammonia/water/methanol (0.2:20:80, 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"-deethylationmetabolite, 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 lowmatrix 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).
[1]Jilin Univ, Res Ctr Drug Metab, Changchun, Peoples R China.
[2]Jilin Univ, Sch Life Sci, Changchun, Peoples R China.
[3]Jilin Univ, Sch Pharmaceut Sci, Changchun, Peoples R China.
[4]Jilin Univ, Hosp 1, Clin Pharmacol Ctr, Res Inst Translat Med, Changchun 130061, Peoples R China.
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