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Plasma samples were processed by solid\u2010phase extraction and separated on an Inertsil ODS\u20103 (4 \u03bcm) column using an 0.1% formic acid in water\u20130.1% formic acid in methanol gradient. Detection of the analytes was conducted in the positive multiple reaction monitoring mode. The range of quantitation was 1\u20131000\u2009ng\/mL for morphine, morphine\u20103\u2010glucuronide and morphine\u20106\u2010glucuronide, and 0.25\u2013100\u2009ng\/mL for clonidine. Intra\u2010day and inter\u2010day accuracy and precision were\u2009\u226415% for all analytes across the quantitation range. Extraction recovery rates were\u2009\u226594% for morphine, \u226590% for M3G, \u226587% for M6G and\u2009\u2265\u200979% for clonidine. Matrix effect ranged from 85\u201394% for clonidine to 101\u2013106% for M3G. The method fulfilled all predetermined acceptance criteria and required only 100\u2009\u03bcL of starting plasma volume. Furthermore, it was successfully applied to 30 clinical trial plasma samples.<\/jats:p>","DOI":"10.1002\/bmc.4527","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T12:50:35Z","timestamp":1551703835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Validation of a HPLC\/MS method for simultaneous quantification of clonidine, morphine and its metabolites in human plasma"],"prefix":"10.1002","volume":"33","author":[{"given":"Fei","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Kentucky  Lexington KY USA"},{"name":"Center for Pharmaceutical Research and Innovation, College of Pharmacy University of Kentucky  Lexington KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrietta","family":"Bada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine University of Kentucky  Lexington KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chee M.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Kentucky  Lexington KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4314-4533","authenticated-orcid":false,"given":"Markos","family":"Leggas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Kentucky  Lexington KY USA"},{"name":"Center for Pharmaceutical Research and Innovation, College of Pharmacy University of Kentucky  Lexington KY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-0978"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0885-3924(02)00531-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-2377"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1996.03539.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aeg121"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.1997.tb04625.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-011-4775-z"},{"issue":"1","key":"e_1_2_7_9_1","first-page":"1","article-title":"Human UGT2B7 catalyzes morphine glucuronidation","volume":"25","author":"Coffman B. 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