{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T20:52:40Z","timestamp":1761511960597,"version":"build-2065373602"},"reference-count":21,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2004,6,29]],"date-time":"2004-06-29T00:00:00Z","timestamp":1088467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2004,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A reliable and easy to use liquid chromatography\/tandem mass spectrometry (LC\/MS\/MS) method without the use of sample extraction was developed for the simultaneous quantification of urinary concentrations of mephenytoin, a standard phenotyping substrate for the cytochrome P450 enzyme CYP2C19, and its phase I metabolites 4\u2032\u2010hydroxymephenytoin and nirvanol.<\/jats:p>\n                  <jats:p>\n                    Fifty\u2009\u03bcL of urine were diluted with a buffered\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010glucuronidase solution and incubated at 37\u00b0C for 6\u2009h followed by addition of methanol, containing the internal standard 4\u2032\u2010methoxymephenytoin. The chromatographic separation was achieved using a 100\u2009\u00d7\u20093\u2009mm, 5\u2009\u03bc Thermo Electron Aquasil C18 column with a gradient flow, increasing the organic fraction (acetonitrile\/methanol 50:50) of the mobile phase from 10 to 90%. Quantification by triple\u2010stage mass spectrometry (TSQ Quantum, Thermo Electron) was accomplished by negative electrospray ionization in the selected reaction monitoring mode. Linearity was observed for all substances in the concentration range 15\u201310\u2009000\u2009ng\/mL. The lower limit of quantification (LLOQ) was 20 ng\/mL for 4\u2032\u2010hydroxymephenytoin and 30\u2009ng\/mL for nirvanol and mephenytoin, respectively. Intra\u2010 and inter\u2010day inaccuracy did not exceed 9.5% for all substances from LLOQ to 10\u2009000\u2009ng\/mL. Intra\u2010 and inter\u2010day precision were in the range of 0.8\u201310.5%. The method was validated according to international ICH and FDA guidelines and successfully applied for phenotyping of Caucasian male volunteers who received an oral dose of 50\u2009mg mephenytoin. Copyright \u00a9 2004 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/rcm.1539","type":"journal-article","created":{"date-parts":[[2004,6,29]],"date-time":"2004-06-29T07:00:59Z","timestamp":1088492459000},"page":"1675-1680","source":"Crossref","is-referenced-by-count":9,"title":["Quantification of mephenytoin and its metabolites 4\u2032\u2010hydroxymephenytoin and nirvanol in human urine using a simple sample processing method"],"prefix":"10.1002","volume":"18","author":[{"given":"Tobias","family":"Klaassen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Kasel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Harlfinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Fuhr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,6,29]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0090-9556(25)08498-3","volume":"18","author":"Veronese ME","year":"1990","journal-title":"Drug Metab. 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