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题名: Determination of propofol UDP-glucuronosyltransferase (UGT) activities in hepatic microsomes from different species by UFLC-ESI-MS
作者: Liang, Si-Cheng1;  Ge, Guang-Bo1;  Liu, Hui-Xin1;  Shang, Hai-Tao2;  Wei, Hong2;  Fang, Zhong-Ze1;  Zhu, Liang-Liang1;  Mao, Yu-Xi1;  Yang, Ling1
关键词: Ultra-fast liquid chromatography ;  Propofol O-glucuronide ;  Hepatic microsomes ;  Interspecies difference ;  Human individual difference
刊名: JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
发表日期: 2011-01-05
DOI: 10.1016/j.jpba.2010.07.049
卷: 54, 期:1, 页:236-241
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Physical Sciences ;  Life Sciences & Biomedicine
类目[WOS]: Chemistry, Analytical ;  Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ;  Pharmacology & Pharmacy
英文摘要: Propofol O-glucuronidation has been used as probe reaction to phenotype UGT1A9 activity in human liver, thus a sensitive and specific method for determination of propofol O-glucuronide (PG) is urgently desirable. In the current study, a new LC-ESI-MS method for determination of PG in hepatic microsomes from human (HLM), monkey (CyLM), dog (DLM), minipig (PLM), rat (RLM) and mouse (MLM) was developed and validated using 4-methylumbelliferyl-beta-D-glucuronide as an internal standard (IS). PG and IS was separated by a Shim-pack XR-ODS column (100 mm x 2.0 mm, 2.2 mu m, Shimadzu) under gradient conditions with the mobile phase of acetonitrile and water containing 0.2% acetic acid (v/v). The mass spectrometric detection was performed under selected ion monitoring (SIM) for PG at m/z 353 and IS at m/z 351. The assay exhibited linearity over the range 0.05-30 mu M for PG with the correlation coefficient of 0.9995. The intra- and inter-day precision was less than 7.2%, with accuracy in the range 93.8-107.5%. The developed method was successfully used for characterizing interspecies and human individual differences in the O-glucuronidation activity towards propofol, as well as investigating inhibitory effects of androsterone and phenylbutazone on propofol O-glucuronidation in HLM. (c) 2010 Elsevier B.V. All rights reserved.
关键词[WOS]: LIQUID-CHROMATOGRAPHIC ASSAY ;  DRUG GLUCURONIDATION ;  LIVER-MICROSOMES ;  METABOLITES ;  URINE ;  PHARMACOKINETICS ;  PREDICTION
语种: 英语
WOS记录号: WOS:000282863300037
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/142726
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China
2.Third Mil Med Univ, Chongqing, Peoples R China

Recommended Citation:
Liang, Si-Cheng,Ge, Guang-Bo,Liu, Hui-Xin,et al. Determination of propofol UDP-glucuronosyltransferase (UGT) activities in hepatic microsomes from different species by UFLC-ESI-MS[J]. JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS,2011,54(1):236-241.
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