A New Quaternary Ammonium Cysteine Analogue as a Trapping Reagent for Reactive Metabolites Screening

Author(s): Natalia Penner , Xiaojing Liu , Chandra Prakash .

Journal Name: Drug Metabolism Letters

Volume 8 , Issue 1 , 2014

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The novel cysteine-cholamine (Cys-chol) trapping reagent was synthesized by coupling N-(tertbutoxycarbonyl)- S-trityl-L-cysteine with cholamine in the presence of HBTU (O-(benzotriazol-1-yl)- N,N,N',N'-tetramethyluronium hexafluorophosphate), and then deprotecting by trifluoroacetic acid. Cys-chol reagent enhanced the sensitivity of reactive metabolite screening 4 to 20 times without introducing additional sample preparation or derivatization steps. Retention of Cys-chol conjugates on reversed-phase column is higher than for respective GSH conjugates which helps in reduction of background interference. The use of Cys-chol trapping reagent can potentially improve sensitivity and specificity of routine reactive metabolite screening assay in drug discovery.

Keywords: Bioactivation, cysteine-cholamine, glutathione, LC-MS/MS, metabolism, reactive metabolite screening, trapping reagent.

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Article Details

Year: 2014
Page: [36 - 42]
Pages: 7
DOI: 10.2174/1872312808666140606100739

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