期刊
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
卷 54, 期 1, 页码 236-241出版社
ELSEVIER
DOI: 10.1016/j.jpba.2010.07.049
关键词
Ultra-fast liquid chromatography; Propofol O-glucuronide; Hepatic microsomes; Interspecies difference; Human individual difference
资金
- National Key Technology R&D Program of China [2008ZX10208]
- National Basic Research Program of China [2009CB522808]
- DICP Innovation Foundation
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.
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