Identification of Prototype Components and Their Metabolites in Rat Serum, Urine and Feces After Oral Administration of Phellodendri Amurensis Cortex Aqueous Extract by UPLC-Orbitrap Fusion Lumos Tribrid-MS

Li-xin KANG; Zhen-peng XU; Yan LIU; Jing YANG; Bing-you YANG; Hai-xue KUANG

doi:10.13422/j.cnki.syfjx.20211050

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Identification of Prototype Components and Their Metabolites in Rat Serum, Urine and Feces After Oral Administration of Phellodendri Amurensis Cortex Aqueous Extract by UPLC-Orbitrap Fusion Lumos Tribrid-MS

Drug Metabolism | 更新时间：2021-05-17

- Identification of Prototype Components and Their Metabolites in Rat Serum, Urine and Feces After Oral Administration of Phellodendri Amurensis Cortex Aqueous Extract by UPLC-Orbitrap Fusion Lumos Tribrid-MS
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 11, Pages: 139-146(2021)
- 作者机构：
  
  黑龙江中医药大学教育部北药基础与应用研究重点实验室，哈尔滨 150040
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20211050
  CLC： R22;R969.1;R28;O657
- Received：11 December 2020，
  
  Published Online：02 March 2021，
  
  Published：05 June 2021
- 稿件说明：
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康立欣,许振鹏,刘艳等.关黄柏水提物在大鼠血清、尿液和粪便中原型成分及其代谢产物的UPLC-Orbitrap Fusion Lumos Tribrid-MS鉴定[J].中国实验方剂学杂志,2021,27(11):139-146.

KANG Li-xin,XU Zhen-peng,LIU Yan,et al.Identification of Prototype Components and Their Metabolites in Rat Serum, Urine and Feces After Oral Administration of Phellodendri Amurensis Cortex Aqueous Extract by UPLC-Orbitrap Fusion Lumos Tribrid-MS[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(11):139-146.
康立欣,许振鹏,刘艳等.关黄柏水提物在大鼠血清、尿液和粪便中原型成分及其代谢产物的UPLC-Orbitrap Fusion Lumos Tribrid-MS鉴定[J].中国实验方剂学杂志,2021,27(11):139-146. DOI： 10.13422/j.cnki.syfjx.20211050.

KANG Li-xin,XU Zhen-peng,LIU Yan,et al.Identification of Prototype Components and Their Metabolites in Rat Serum, Urine and Feces After Oral Administration of Phellodendri Amurensis Cortex Aqueous Extract by UPLC-Orbitrap Fusion Lumos Tribrid-MS[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(11):139-146. DOI： 10.13422/j.cnki.syfjx.20211050.

摘要

目的

应用超高效液相色谱-四极杆-静电场轨道阱-线性离子阱质谱法（UPLC-Orbitrap Fusion Lumos Tribrid-MS）分析关黄柏水提物在正常大鼠血清、尿液及粪便中的原型成分及其代谢物，探讨关黄柏在大鼠体内的药效物质基础。

方法

采用ACQUITY UPLC

CSH

色谱柱（2.1 mm×100 mm，1.7 μm），以0.1%甲酸水溶液（A）-乙腈（B）为流动相进行梯度洗脱（0~15 min，2%~25%B；15~25 min，25%~50%B；25~28 min，50%~98%B），流速0.3 mL·min

-1

，进样量10 μL，柱温40 ℃。运用加热电喷雾离子源（HESI），扫描范围

100~1 000，正离子模式采集数据。通过比较给药后样品和空白样品的差异，对灌胃给予关黄柏水提物后大鼠血清、尿液和粪便中的原型成分及其代谢产物进行鉴定。

结果

灌胃给予关黄柏水提物后，从大鼠血清、尿液及粪便中鉴定和表征了70个外源性成分，包括15个原型成分和55个代谢产物。其中15个原型成分包括12个生物碱和3个柠檬苦素，55个代谢产物包括52个生物碱和3个柠檬苦素。关黄柏水提物在大鼠体内的代谢途径主要包括脱饱和、甲基化、氧化、硫酸化及葡萄糖醛酸结合等反应。

结论

生物碱在大鼠体内进行Ⅰ相代谢和Ⅱ相代谢，柠檬苦素类在大鼠体内主要进行Ⅰ相代谢，可为进一步解析关黄柏体内过程，阐明其药效物质基础提供实验依据。

Abstract

Objective

An ultra-performance liquid chromatography coupled with Orbitrap Fusion Lumos Tribrid mass spectrometry （UPLC-Orbitrap Fusion Lumos Tribrid-MS） was applied to analyze the prototypes and their metabolites of Phellodendri Amurensis Cortex aqueous extract in the serum， urine and feces of normal rats， and to investigate the pharmacodynamic material basis of Phellodendri Amurensis

Cortex in rats.

Method

Chromatographic separation was performed on the ACQUITY UPLC

CSH

column （2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-15 min， 2%-25%B； 15-25 min， 25%-50%B； 25-28 min， 50%-98%B）， flow rate was 0.3 mL·min

-1

， the injection volume was 10 μL and the column temperature was 40 ℃. Heated electrospray ionization （HESI） was used to collect data in the positive ion modes with the scanning range of

100-1 000. By comparing chromatogram differences between the blank samples and the samples after administration， prototypes and their metabolites of biological samples after oral administration of Phellodendri Amurensis Cortex aqueous extract were identified.

Result

After oral administration of Phellodendri Amurensis Cortex aqueous extract， a total of 70 compounds including 15 prototypes and 55 metabolites in rat serum， urine and feces were detected. Among them， 15 prototypes included 12 alkaloids and 3 limonoids， and 55 metabolites included 52 alkaloids and 3 limonoids. Desaturation， methylation， oxidation， sulfonation and glucuronide conjugation were observed as the primary metabolic pathways for the chemical constituents of Phellodendri Amurensis Cortex aqueous extract.

Conclusion

Alkaloids in Phellodendri Amurensis Cortex aqueous extract undergo phase Ⅰ and phase Ⅱ metabolism in rats， and limonoids mainly undergo phase Ⅰ metabolism in rats. This paper can provide experimental basis for further analyzing the process

in vivo

of Phellodendri Amurensis Cortex and elucidating its pharmacodynamic substance basis

关键词

Keywords

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