{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:09:21Z","timestamp":1790172561378,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"name":"EU-FP7 Neo-Opioid","award":["223767"],"award-info":[{"award-number":["223767"]}]},{"name":"EU-FP7 Neo-Opioid","award":["HEALTH-2007-4.2-1"],"award-info":[{"award-number":["HEALTH-2007-4.2-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Morphine is still the mainstay in treatment of severe pain and is metabolized in the liver mainly by glucuronidation, partly to the pharmacologically active morphine\u20106\u2010glucuronide (M6G). The sulfation pathway has attracted much less attention but may also form active metabolites. The aim of the present study was to study two sulfate metabolites of morphine in humans. Urine and plasma from newborns, adult heroin addicts, and terminal cancer patients was analyzed for the presence of morphine\u20103\u2010sulfate (M3S) and morphine\u20106\u2010sulfate (M6S) by a new liquid chromatography \u2013 tandem mass spectrometry (<jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>) method. In addition, morphine sulfation was studied in vitro in human liver cytosol preparations. M3S was present in urine and plasma from all study groups although at lower concentrations than morphine\u20103\u2010glucuronide (M3G). The plasma M3S\/M3G ratio was 30 times higher in newborns than in adults indicating that the relative sulfation is more important at early stage of life. M6S was measurable in only one plasma sample from a newborn patient, and in one of the urine sample from the drug testing group. The incubation of morphine with liver cytosol extracts resulted in approximately equal rate of formation of both M3S and M6S. In conclusion, sulfation of morphine is catalyzed in human liver but this minor metabolic pathway probably lacks clinical significance. The M6S metabolite is formed at a low rate, making it undetectable in most individuals.<\/jats:p>","DOI":"10.1002\/prp2.71","type":"journal-article","created":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T02:18:06Z","timestamp":1409624286000},"source":"Crossref","is-referenced-by-count":14,"title":["Detection of morphine\u20103\u2010sulfate and morphine\u20106\u2010sulfate in human urine and plasma, and formation in liver cytosol"],"prefix":"10.1002","volume":"2","author":[{"given":"Maria","family":"Andersson","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Department of Laboratory Medicine Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Bj\u00f6rkhem\u2010Bergman","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Ekstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Laboratory Medicine Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Bergqvist","sequence":"additional","affiliation":[{"name":"Department of Woman and Child Health Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Lagercrantz","sequence":"additional","affiliation":[{"name":"Department of Woman and Child Health Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Rane","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Laboratory Medicine Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof","family":"Beck","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Laboratory Medicine Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199810000-00020"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201100739"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.1486"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1980.102"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198814040-00001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140010-00003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.212258"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1990.tb05458.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.05.060"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.093633"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.049197"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm434"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(95)02067-5"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2014.05.003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0749-0690(18)30232-5","article-title":"Death and dying and recognizing approaching death","volume":"12","author":"Long MC","year":"1996","journal-title":"Clin Geriatr Med"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-013-1007-6"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602539608994011"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1992.42"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/0049825031000121608"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.1982.tb01855.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.2174\/157488406775268219"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1981.214"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00609900"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1983.tb02148.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2013.00088"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(00)80494-6"}],"container-title":["Pharmacology Research &amp; 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