中國實驗方劑學(xué)雜志 第29卷 第20期 2023年10月

［Abstract］  Objective： Ultra-high performance liquid chromatography-quadrupole-electrostatic field 
orbitrap high resolution mass spectrometry（UHPLC-Q-Orbitrap HRMS） was used to identify the metabolites 
of limonin in rats， and to explore the gender differences in the distribution of prototype components andmetabolites in rats after single dose intragastric administration of limonin， as well as to speculate the metabolic 
pathways. Method： The separation was performed on a Thermo Scientific Accucore? C18 column（3 mm× 100 mm， 2.6 μm） with 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） as  mobile phase in a gradient elution mode（0-1 min， 5%B； 1-6 min， 5%-20%B； 6-18 min， 20%-50%B； 18- 23 min， 50%-80%B； 23-25 min， 80%-95%B； 25-30 min， 95%B） at a flow rate of 0.3 mL·min-1 and a 
column temperature of 30 ℃. MS data of biological samples were collected under the positive ion mode of 
electrospray ionization（ESI） and in the scanning range of m/z 100-1 500. Plasma， tissues（heart， liver，  spleen， lung， kidney， stomach and small intestine）， urine and fecal samples were collected and prepared after 
intragastric administration， and the prototype component and metabolites of limonin were identified. Result：  The prototype component of limonin were detected in the feces， stomach， small intestine of female and male  rats， and in the heart， liver， spleen， lung and kidney tissues of female rats. A total of 23 metabolites related to  limonin were detected in rats， of which 2， 1， 5， 4， 23 metabolites were detected in liver， stomach， small  intestine， urine and feces， respectively， and the main metabolic pathways were hydrolysis， reduction，  hydroxylation and methylation， etc. The distribution of some metabolites differed between male and female  rats. Conclusion： The prototype component of limonin are mainly distributed in the stomach and small  intestine in rats， and the distribution of prototype component and some metabolites are different by gender. 
Limonin is mainly excreted through feces with phase Ⅰ metabolites as the main ones. The results of this study 
can provide a reference for further elucidation of the effect of gender differences on the metabolism of limonin  in vivo and its mechanism of action.

本研究中對照品：檸檬苦素 購自于四川恒誠致遠(yuǎn)生物科技有限公司（Naturewill biotechnology Co., Ltd.）