{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T13:58:42Z","timestamp":1761487122243,"version":"build-2065373602"},"reference-count":12,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,2,3]],"date-time":"2004-02-03T00:00:00Z","timestamp":1075766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Mass Spectrom."],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>DB75 (2,5\u2010bis(4\u2010amidinophenyl)furan) is a promising antimicrobial agent against African trypanosomiasis and <jats:italic>Pneumocystis carinii<\/jats:italic> pneumonia. However, it suffers from poor oral activity in rodent models for both infections. In contrast, a novel prodrug of DB75, 2,5\u2010bis(4\u2010amidinophenyl)furan\u2010bis\u2010<jats:italic>O<\/jats:italic>\u2010methylamidoxime (DB289), has excellent oral activity. DB289 is currently undergoing clinical investigation as a candidate drug to treat primary stage African trypanosomiasis and <jats:italic>Pneumocystis carinii<\/jats:italic> pneumonia. In this study, metabolites of DB289 formed after incubation with freshly isolated rat hepatocytes were characterized using liquid chromatography\/ion trap mass spectrometry. Administration of DB289 and octadeuterated DB289 in a 1 : 1 mixture greatly facilitated metabolite identification by providing isotope patterns with twin ions separated by 8 <jats:italic>m<\/jats:italic>\/<jats:italic>z<\/jats:italic> units in the ratio 1 : 1, in the extracted ion chromatograms of molecular ions and in the product ion mass spectra of metabolites. Ten metabolites were identified. Series of <jats:italic>O<\/jats:italic>\u2010demethylations and <jats:italic>N<\/jats:italic>\u2010dehydroxylations led to the metabolic activation of DB289 to DB75 with the production of four intermediate phase I metabolites. Phase II glucuronidation and sulfation led to the formation of four glucuronide and one sulfate metabolites. Copyright \u00a9 2004 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jms.591","type":"journal-article","created":{"date-parts":[[2004,3,29]],"date-time":"2004-03-29T03:04:41Z","timestamp":1080529481000},"page":"351-360","source":"Crossref","is-referenced-by-count":26,"title":["Metabolites of an orally active antimicrobial prodrug, 2,5\u2010bis(4\u2010amidinophenyl)furan\u2010bis\u2010<i>O<\/i>\u2010methylamidoxime, identified by liquid chromatography\/tandem mass spectrometry"],"prefix":"10.1002","volume":"39","author":[{"given":"Lian","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhiren R.","family":"Thakker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert D.","family":"Voyksner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariappan","family":"Anbazhagan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Boykin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard R.","family":"Tidwell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,2,3]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"561","volume-title":"Pneumocystis Carinii Pneumonia","author":"Tidwell RR","year":"1993"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlac.197519750115"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00214a014"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm970570i"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(81)90099-0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(96)00557-4"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.444"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)61797-5"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020957430400"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.676"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/bms.1200141121"},{"key":"e_1_2_6_13_2","first-page":"830","article-title":"N+\u2010glucuronidation, a common pathway in human metabolism of drugs with a tertiary amine group","volume":"26","author":"Hawes EM","year":"1998","journal-title":"Drug Metab. Dispos."}],"container-title":["Journal of Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjms.591","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jms.591","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T14:56:57Z","timestamp":1760626617000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jms.591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,3]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,4]]}},"alternative-id":["10.1002\/jms.591"],"URL":"https:\/\/doi.org\/10.1002\/jms.591","archive":["Portico"],"relation":{},"ISSN":["1076-5174","1096-9888"],"issn-type":[{"type":"print","value":"1076-5174"},{"type":"electronic","value":"1096-9888"}],"subject":[],"published":{"date-parts":[[2004,2,3]]}}}