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采用 UHPLC 结合傅里叶变换离子回旋共振质谱法研究库狄氏注射液在大鼠体内的代谢产物谱。

Metabolic profile of Kudiezi injection in rats by UHPLC coupled with Fourier transform ion cyclotron resonance mass spectrometry.

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.

School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, China.

出版信息

J Sep Sci. 2018 Feb;41(3):774-788. doi: 10.1002/jssc.201700831. Epub 2017 Dec 18.

DOI:10.1002/jssc.201700831
PMID:29131518
Abstract

In this study, a reliable and sensitive ultra-high performance liquid chromatography coupled with fourier transform ion cyclotron resonance mass spectrometry method was developed for the systematic study of the metabolic profile of Kudiezi injection in rat plasma, bile, urine, and feces after intravenous administration of a single dose. The chromatographic separation was performed on an Agilent Eclipse Plus C column (4.6 mm × 50 mm, 1.8 μm) and the identification of prototype components and metabolites was achieved on a Bruker Solarix 7.0 T ultra-high resolution spectrometer in negative ion mode. Results indicated that a total of 76 constituents including 29 prototype compounds and 47 metabolites (10 phase I metabolites and 37 phase II metabolites) were tentatively identified. And the metabolic pathways of these prototype compounds including hydroxylation, dehydrogenation, glucuronidation, and sulfate conjugation. In conclusion, the developed method with high resolution and sensitivity was effective for screening and identification of prototypes and metabolites of Kudiezi injection in vivo. Moreover, these results would provide significant information for further pharmacokinetic and pharmacological research of Kudiezi injection in vivo.

摘要

在这项研究中,建立了一种可靠且灵敏的超高效液相色谱-傅里叶变换离子回旋共振质谱联用方法,用于系统研究单次静脉注射苦参注射液在大鼠血浆、胆汁、尿液和粪便中的代谢谱。色谱分离在安捷伦 Eclipse Plus C 柱(4.6mm×50mm,1.8μm)上进行,在布鲁克 Solarix 7.0 T 超高分辨率质谱仪上以负离子模式进行原型成分和代谢物的鉴定。结果表明,共鉴定出 76 种成分,包括 29 种原型化合物和 47 种代谢物(10 种 I 相代谢物和 37 种 II 相代谢物)。这些原型化合物的代谢途径包括羟化、脱氢、葡萄糖醛酸化和硫酸结合。总之,该方法具有高分辨率和灵敏度,可有效用于苦参注射液原型及其代谢物的体内筛选和鉴定。此外,这些结果将为苦参注射液在体内的药代动力学和药理学研究提供重要信息。

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