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The present study was to elucidate metabolic difference of harmaline and harmine in 11 mammalian liver microsomes in order to quantitate species\u2010specific metabolic profiles. Using the probe substrate reaction, the enzymatic activities for 8 CYP450 isozymes of 11 liver microsomes were characterized. Combining ultra performance liquid chromatography combined with electrospray ionization quadrupole time\u2010of\u2010flight tandem mass spectrometry (UPLC\u2010ESI\u2010Q\/TOF\u2010MS) and ultra performance liquid chromatography combined with electrospray ionization quadrupole tandem mass spectrometry (UPLC\u2010ESI\u2010MS\/MS) methods, 18 metabolites for harmaline and 11 for harmine were identified. The metabolism patterns differences of them presented discrepancy in the quality and quantity of metabolites. It was notable that <jats:italic>O<\/jats:italic>\u2010sulfate conjugation was detected in all species except sheep. The intrinsic clearance <jats:italic>CL<\/jats:italic><jats:sub><jats:italic>int<\/jats:italic>, <jats:italic>LM<\/jats:italic><\/jats:sub> values for the metabolites harmine and harmol in rabbits (37.5 and 42.4\u2009\u03bcL\/min\/mg) were higher than those in other animals, while dogs (16.2 and 16.7\u2009\u03bcL\/min\/mg) and humans (16.0 and 16.3\u2009\u03bcL\/min\/mg) exhibited similar <jats:italic>in vitro<\/jats:italic> metabolic clearance. These observations suggested that harmaline and harmine were rapidly metabolized in liver microsomes of rat, mouse, and rabbit; moderately metabolized in human and dog; while weakly metabolized in sheep. Comprehensive analysis of the metabolism indicated that dogs and humans showed considerable similarity in the elimination of parent drugs, metabolic profiles, and catalytic processes. To summarize, these findings illustrated that <jats:italic>in vitro<\/jats:italic> studies of harmaline and harmine metabolic profiles in different species are helpful for the proper selection and interpretation of animal models for pharmacological and toxicological evaluation, and will ultimately provide useful guidance for the development of \u03b2\u2010carboline alkaloids. Copyright \u00a9 2016 John Wiley &amp; Sons Ltd.<\/jats:p>","DOI":"10.1002\/dta.2028","type":"journal-article","created":{"date-parts":[[2016,7,5]],"date-time":"2016-07-05T10:29:00Z","timestamp":1467714540000},"page":"754-768","source":"Crossref","is-referenced-by-count":26,"title":["Interspecies metabolic diversity of harmaline and harmine in <i>in vitro<\/i> 11 mammalian liver microsomes"],"prefix":"10.1002","volume":"9","author":[{"given":"Shuping","family":"Li","sequence":"first","affiliation":[{"name":"<i>Institute of Chinese Materia Medica<\/i> Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Teng","sequence":"additional","affiliation":[{"name":"<i>Institute of Chinese Materia Medica<\/i> Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine  Shanghai China"},{"name":"<i>Pharmacy Department<\/i> the First Affiliated Hospital of Xinjiang Medical University  Urumqi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"<i>Institute of Chinese Materia Medica<\/i> Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Cheng","sequence":"additional","affiliation":[{"name":"<i>Institute of Chinese Materia Medica<\/i> Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine  Shanghai China"},{"name":"<i>Shanghai R&amp;D Centre for Standardization of Chinese Medicines<\/i>  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Jiang","sequence":"additional","affiliation":[{"name":"<i>Institute of Chinese Materia Medica<\/i> Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengtao","family":"Wang","sequence":"additional","affiliation":[{"name":"<i>Institute of Chinese Materia Medica<\/i> Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine  Shanghai China"},{"name":"<i>Shanghai R&amp;D Centre for Standardization of Chinese Medicines<\/i>  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changhong","family":"Wang","sequence":"additional","affiliation":[{"name":"<i>Institute of Chinese Materia Medica<\/i> Shanghai University of Traditional Chinese Medicine; The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine  Shanghai China"},{"name":"<i>Shanghai R&amp;D Centre for Standardization of Chinese Medicines<\/i>  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2014.08.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2012.03.024"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.3458"},{"key":"e_1_2_8_5_1","article-title":"Acetylcholinesterase and butyrylcholinesterase inhibitory activities of \u03b2\u2010carboline and quinoline alkaloids derivatives from the plants of genus Peganum","author":"Zhao T.","year":"2013","journal-title":"J. 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