{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:29:03Z","timestamp":1761596943357,"version":"build-2065373602"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T00:00:00Z","timestamp":1137024000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Separation Science"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lorazepam (LOR) is a 3\u2010hydroxy\u20101,4\u2010benzodiazepine that is chiral and undergoes enantiomerization at room temperature. In humans, about 75% of the administered dose of LOR is excreted in the urine as its 3O\u2010glucuronide. CE\u2010MS with negative ESI was used to confirm the presence of LOR\u20103O\u2010glucuronide in urines that stemmed from a healthy individual who ingested 1 or 2 mg LOR, whereas free LOR could be detected in extracts prepared from enzymatically hydrolyzed urines. As the 3O\u2010glucuronidation reaction occurs at the chiral center of the molecule, two diastereoisomers can theoretically be formed, molecules that can no longer interconvert. The stereoselective formation of LOR glucuronides in humans and<jats:italic> in vitro <\/jats:italic>was investigated. MEKC analysis of extracts of the nonhydrolyzed urines suggested the presence of the two different LOR glucuronides in the urine. The formation of the same two diastereoisomers was also observed <jats:italic>in vitro<\/jats:italic> employing incubations of LOR with human liver microsomes in the presence of uridine 5\u2032\u2010diphospho\u2010glucuronic acid as coenzyme. The absence of other coenzymes excluded the formation of phase I or other phase II metabolites of LOR. Both results revealed a stereoselectivity, one diastereoisomer being formed in a higher amount than the other. After enzymatic hydrolysis using \u03b2\u2010glucuronidase, these peaks could not be detected any more. Instead, LOR was monitored. Analysis of the extracts prepared from enzymatically hydrolyzed urines by MEKC in the presence of 2\u2010hydroxypropyl\u2010\u03b2\u2010CD revealed the enantiomerization process of LOR (observation of two peaks of equal magnitude connected with a plateau zone). The data presented provide for the first time the evidence of the stereoselectivity of the LOR glucuronidation in humans.<\/jats:p>","DOI":"10.1002\/jssc.200500268","type":"journal-article","created":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T07:18:23Z","timestamp":1137050303000},"page":"153-163","source":"Crossref","is-referenced-by-count":18,"title":["Analysis of lorazepam and its 3O\u2010glucuronide in human urine by capillary electrophoresis: Evidence for the formation of two distinct diastereoisomeric glucuronides"],"prefix":"10.1002","volume":"29","author":[{"given":"Andrea","family":"Baldacci","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Thormann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,12]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1976203329"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1977212222"},{"key":"e_1_2_1_4_2","unstructured":"Moffat A. 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