Rapid and sensitive liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of yonkenafil and its major metabolites in rat plasma.
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 (60:40, v/v), and the baseline separation was achieved on Zorbax SB-C18column 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'-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).
Research Center for Drug Metabolism, Jilin University, Changchun, P. R. China.
Heping
H
Sun
School of Life Sciences, Jilin University, Changchun, P. R. China.
Jiang
J
Wang
School of Pharmaceutical Sciences, Jilin University, Changchun, P. R. China.
Yantong
Y
Sun
Research Center for Drug Metabolism, Jilin University, Changchun, P. R. China.
Wenwen
W
Peng
Research Center for Drug Metabolism, Jilin University, Changchun, P. R. China.
Lingxia
L
Sun
School of Life Sciences, Jilin University, Changchun, P. R. China.
Yan
Y
Yang
Research Center for Drug Metabolism, Jilin University, Changchun, P. R. China. gujk@jlu.edu.cn.|Clinical Pharmacology Center, Research Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, P. R. China. gujk@jlu.edu.cn.
Jingkai
J
Gu
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015394:Molecular Structure; D010949:Plasma / Q000737:chemistry; D011744:Pyrimidinones / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D011758:Pyrroles / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
D011744:Pyrimidinones; D011758:Pyrroles; C000613072:yonkenafil
Liquid chromatography; Mass spectrometry; Metabolites; Pharmacokinetics; Yonkenafil