title: Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS.
abstract: Context The β-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats.
authors.affiliation: a The MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine , Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine , Shanghai , China ;|b Department of Pharmacy , The First Affiliated Hospital of Xinjiang Medical University , Urumqi , China ;
authors.forename: Shuping
authors.initials: S
authors.lastname: Li
authors.affiliation: a The MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine , Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine , Shanghai , China ;|b Department of Pharmacy , The First Affiliated Hospital of Xinjiang Medical University , Urumqi , China ;
authors.forename: Liang
authors.initials: L
authors.lastname: Teng
authors.affiliation: a The MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine , Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine , Shanghai , China ;
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: a The MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine , Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine , Shanghai , China ;|c Shanghai R&D Centre for Standardization of Chinese Medicines , Shanghai , China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Cheng
authors.affiliation: a The MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine , Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine , Shanghai , China ;
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: a The MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine , Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine , Shanghai , China ;|c Shanghai R&D Centre for Standardization of Chinese Medicines , Shanghai , China.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a The MOE Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine , Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine , Shanghai , China ;|c Shanghai R&D Centre for Standardization of Chinese Medicines , Shanghai , China.
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D005260:Female; D006213:Hallucinogens / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006247:Harmine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D016014:Linear Models; D008297:Male; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D013431:Sulfates / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D006213:Hallucinogens; D013431:Sulfates; D006247:Harmine; C005010:harman
keywords: metabolic profile; semiquantitative determination; β-Carboline alkaloid