{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:32:07Z","timestamp":1760920327801,"version":"build-2065373602"},"reference-count":24,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T00:00:00Z","timestamp":1473206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81430087","81473142","81102383"],"award-info":[{"award-number":["81430087","81473142","81102383"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Separation Science"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p>Yonkenafil is a promising drug for treatment of male erectile dysfunction. Previous studies showed that the piperazine\u2010<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2019\u2010deethylation metabolite, piperazine\u2010<jats:italic>N<\/jats:italic>\u2010deethylation metabolite, and piperazine\u2010<jats:italic>N<\/jats:italic>\u2010deethylation\u2010<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2019\u2010deethylation 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\u2010throughput liquid chromatography with tandem mass spectrometry. Analytes and internal standard were extracted from a small quantity of plasma (50 \u03bcL) using liquid\u2013liquid extraction with diethyl ether\/dichloromethane (60:40, v\/v), and the baseline separation was achieved on Zorbax SB\u2010C<jats:sub>18<\/jats:sub> 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\u2010reaction monitoring mode within 2 min. Calibration curve of the method was linear within the range of 1.00\u20131000 ng\/mL for all the analytes with the intra\u2010 and interday precisions of 4.0\u20135.2 and 4.0\u20135.3% for yonkenafil, 3.1\u20134.9 and 3.1\u20135.2% for the piperazine\u2010<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2019\u2010deethylation metabolite, 4.8\u20136.8 and 4.8\u20137.3% for the piperazine\u2010<jats:italic>N<\/jats:italic>\u2010deethylation metabolite, and 2.9\u20136.1 and 5.4\u20136.3% for the piperazine\u2010<jats:italic>N<\/jats:italic>\u2010deethylation\u2010<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2019\u2010deethylation 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).<\/jats:p>","DOI":"10.1002\/jssc.201600445","type":"journal-article","created":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T05:43:44Z","timestamp":1473227024000},"page":"3700-3708","source":"Crossref","is-referenced-by-count":5,"title":["Rapid and sensitive liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of yonkenafil and its major metabolites in rat plasma"],"prefix":"10.1002","volume":"39","author":[{"given":"Heping","family":"Sun","sequence":"first","affiliation":[{"name":"Research Center for Drug Metabolism Jilin University  Changchun P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Jilin University  Changchun P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yantong","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Jilin University  Changchun P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwen","family":"Peng","sequence":"additional","affiliation":[{"name":"Research Center for Drug Metabolism Jilin University  Changchun P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingxia","family":"Sun","sequence":"additional","affiliation":[{"name":"Research Center for Drug Metabolism Jilin University  Changchun P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Jilin University  Changchun P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingkai","family":"Gu","sequence":"additional","affiliation":[{"name":"Research Center for Drug Metabolism Jilin University  Changchun P. R. China"},{"name":"Clinical Pharmacology Center, Research Institute of Translational Medicine The First Hospital of Jilin University  Changchun P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,9,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2011.02473.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201200280"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200900841"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/14746514020020040801"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2014.12.011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.3378"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.6604"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201501339"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2008.04.004"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2011.09.029"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201100496"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2015.12.004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sxmr.2015.10.004"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.10.003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-052914-091923"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/acupmed-2014-010634"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2014.12.030"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.07.007"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2015.07.002"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9293-0"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-6109.2011.02244.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2016.04.033"},{"issue":"1","key":"e_1_2_8_24_1","first-page":"165","article-title":"LC\u2013MS\u2013MS determination of troxerutin in plasma and its application to a pharmacokinetic study","volume":"73","author":"Cui X.","year":"2010","journal-title":"Chromatographia"},{"volume-title":"Guidance for Industry: Bioanalytical Method Validation","year":"2011","author":"U.FDA","key":"e_1_2_8_25_1"}],"container-title":["Journal of Separation Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjssc.201600445","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jssc.201600445","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T11:30:28Z","timestamp":1760873428000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jssc.201600445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,7]]},"references-count":24,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1002\/jssc.201600445"],"URL":"https:\/\/doi.org\/10.1002\/jssc.201600445","archive":["Portico"],"relation":{},"ISSN":["1615-9306","1615-9314"],"issn-type":[{"type":"print","value":"1615-9306"},{"type":"electronic","value":"1615-9314"}],"subject":[],"published":{"date-parts":[[2016,9,7]]}}}