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A liquid chromatography/tandem mass spectrometry method for detecting UGT‐mediated bioactivation of drugs as their N ‐acetylcysteine adducts in human liver microsomes by Hiroshi Harada; Takuro Endo; Yasunori Momose; Hiroshi Kusama is a Chemistry article available to read on EtoBox.

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## Abstract The detection of the reactive metabolites of drugs has recently been gaining increasing importance. __In vitro__ trapping studies using trapping agents such as glutathione are usually conducted for the detection of reactive metabolites, especially those of cytochrome P450‐mediated metabolism. In order to detect the UDP‐glucuronosyltransferase (UGT)‐mediated bioactivation of drugs, an __in__ __vitro__ trapping method using __N__‐acetylcysteine (NAC) as a trapping agent followed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed in this study. After the test compounds (diclofenac and ketoprofen) had been incubated in human liver microsomes with uridine diphosphoglucuronic acid (UDPGA) and NAC, the NAC adducts formed through their acyl glucuronides were analyzed using LC/MS/MS with electrospray ionization (ESI). The NAC adduct showed a mass shift of 145 units as compared to its parent, and the characteristic ion fragmentations reflected the parent. This is a concise and high‐throughput method for evaluating reactive metabolites by UGT‐mediated bioactivation. Copyright © 2009 John Wiley & Sons, Ltd.

Who reads A liquid chromatography/tandem mass spectrometry method for detecting UGT‐mediated bioactivation of drugs as their N ‐acetylcysteine adducts in human liver microsomes?

Author

Hiroshi Harada; Takuro Endo; Yasunori Momose; Hiroshi Kusama

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0951-4198)

Published

2009

Language

EN

Field

Chemistry (Physical Sciences)