Metabolites identification of harmane in vitro/in vivo in rats by ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.
Harmane, a β-carboline alkaloid with a wide spectrum of pharmacological activities, is naturally present in the human diet, in numerous foodstuffs and in hallucinogenic plants such as Peganum harmala, Banisteriopsis caapi and Tribulus terrestris. However, the precise metabolic fate of harmane remains unknown. In order to know whether harmane is extensively metabolized, a rapid and sensitive method using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC/ESI-QTOF-MS) was used to analyze the metabolic profile of harmane in vitro and in vivo in rats. A total of 21 metabolites were identified from the rat liver microsomes and rat liver S9 (9), rat urine (11), feces (16), bile (16), and plasma (10) after a single oral administration of harmane using MetaboLynx™ and MassFragment ™ software tools. It indicated that the biliary and faecal clearance were the major excretion routes for harmane as well as its metabolites. The specific CLogP values combined with different acidic and alkaline mobile phase were helpful and useful for distinguishing N-oxidation and monohydroxylation metabolites. The metabolic transformation pathways of harmane included monohydroxylation, dihydroxylation, N-oxidation, O-glucuronide conjugation, O-sulphate conjugation, and glutathione conjugation. In conclusion, this study showed an insight into the metabolism of harmane.
Institute of Chinese Materia Medica, 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, 1200 Cailun Rood, Shanghai 201210, China; College of Pharmacy, Xinjiang Medical University, Urumuqi 830054, China.
Shuping
S
Li
Institute of Chinese Materia Medica, 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, 1200 Cailun Rood, Shanghai 201210, China.
Wei
W
Liu
Institute of Chinese Materia Medica, 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, 1200 Cailun Rood, Shanghai 201210, China; College of Pharmacy, Xinjiang Medical University, Urumuqi 830054, China. Electronic address: tl750212@126.com.
Liang
L
Teng
Institute of Chinese Materia Medica, 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, 1200 Cailun Rood, Shanghai 201210, China; Shanghai R&D Centre for Standardization of Chinese Medicines, 199 Guoshoujing Road, Shanghai 201210, China.
Xuemei
X
Cheng
Institute of Chinese Materia Medica, 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, 1200 Cailun Rood, Shanghai 201210, China; Shanghai R&D Centre for Standardization of Chinese Medicines, 199 Guoshoujing Road, Shanghai 201210, China.
Zhengtao
Z
Wang
Institute of Chinese Materia Medica, 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, 1200 Cailun Rood, Shanghai 201210, China; Shanghai R&D Centre for Standardization of Chinese Medicines, 199 Guoshoujing Road, Shanghai 201210, China. Electronic address: wchcxm@hotmail.com.
Changhong
C
Wang
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005243:Feces / Q000737:chemistry; D006247:Harmine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008297:Male; D055442:Metabolome; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
D006247:Harmine; C005010:harman
Harmane; Metabolites; UPLC/ESI-QTOF-MS; β-Carboline alkaloid