Methanol adducts leading to the identification of a reactive aldehyde metabolite of CPAQOP in human liver microsomes by ultra-high-performance liquid chromatography/mass spectrometry

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• 作者：Scott Martin ; Eva M. Lenz ; Robin Smith ; David G. Temesi ; Alexandra L. Orton and Malcolm R. Clench
• 刊名：Rapid Communications in Mass Spectrometry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：31
• 期：1
• 页码：145-151
• 全文大小：995K
• ISSN：1097-0231

文摘

The incubation of CPAQOP (1-[(2R)-2-[[4-[3-chloro-4-(2-pyridyloxy)anilino]quinazolin-5-yl]oxymethyl]-1-piperidyl]-2-hydroxy) with human liver microsomes generated several metabolites that highlighted the hydroxyacetamide side chain was a major site of metabolism for the molecule. The metabolites were derived predominantly from oxidative biotransformations; however, two unexpected products were detected by liquid chromatography/ultraviolet/mass spectrometry (LC/UV/MS) and identified as methanol adducts. This observation prompted further LC/MS investigations into their formation.