Analysis on Metabolites and Metabolic Pathways of Harmine in Rats by UPLC-Q-TOF-MS
10.13422/j.cnki.syfjx.20240464
- VernacularTitle:去氢骆驼蓬碱在大鼠体内代谢产物与代谢途径的UPLC-Q-TOF-MS分析
- Author:
Kurban CARTIERA
1
;
Changhong WANG
2
;
Nan XU
1
;
Qinwei XU
1
;
Liang TENG
3
;
Huijing GAO
3
Author Information
1. School of Pharmacy，Xinjiang Medical University，Urumqi 830011，China
2. Institute of Chinese Materia Medica，Shanghai University of Traditional Chinese Medicine， Shanghai 201203，China
3. State Key Laboratory of Pathogenesis， Prevention and Treatment of High Incidence Diseases in Central Asia， The First Affiliated Hospital of Xinjiang Medical University，Urumqi 830054，China
- Publication Type:Journal Article
- Keywords:
harmine;
ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）;
metabolites;
metabolic pathways;
plasma;
bile;
urine
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(11):202-209
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the metabolites of harmine in rats， in order to explore the differences in distribution of metabolites in rats after single dose（40 mg·kg-1） intragastric administration of harmine， as well to speculate the metabolic pathways. MethodSD rats were given a single dose of harmine by intragastric administration. Plasma， bile， urine and feces samples were collected after administration， and the samples were processed for determination by UPLC-Q-TOF-MS. The separation was performed on an ACQUITY UPLC™ HSS T3 columu（2.1 mm×100 mm， 1.8 μm） with acetonitrile（A）-0.1% formic acid aqueous solution（B） as mobile phase for gradient elution（0-2 min， 5%A； 2-9 min， 5%-35%A； 9-9.5 min， 35%-100%A； 9.5-12 min， 100%A； 12-12.5 min， 100%-5%A； 12.5-14 min， 5%A）， the mass spectra were obtained in positive ion mode with electrospray ionization（ESI）， the scanning range was m/z 50-1 200. The metabolites of harmine were identified based on the information of the obtained compounds and the literature data， and the metabolic pathways were hypothesized. ResultA total of 42 compounds（harmine and its metabolites） were identified in rats， including 27 in plasma， 17 in bile， 26 in urine and 13 in feces. The metabolic pathways involved in these 42 metabolites included monohydroxylation， dihydroxylation， demethylation， glucuronidation and sulfation. ConclusionHarmine can undergo phase Ⅰ and phase Ⅱ metabolic reactions in rats， and the prototype drug is metabolized rapidly in vivo， and the metabolites are mainly excreted by the kidneys， which can provide a reference basis for the pharmacodynamics and material basis of harmine.
