The use of alkoxycarbonyl derivatives for the mass spectral analysis of drug-thioether metabolites. Studies with the cysteine, mercapturic acid and glutathione conjugates of acetaminophen.

The use of alkoxycarbonyl derivatives for the mass spectral analysis of drug-thioether metabolites. Studies with the cysteine, mercapturic acid and glutathione conjugates of acetaminophen.
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使用烷氧基羰基衍生物对药物硫醚代谢物进行质谱分析。

DOI:
10.1002/bms.1200151202
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发表时间:
1988
期刊:
Biomedical & environmental mass spectrometry
影响因子:
--
通讯作者:
Baillie,TA
Baillie,TA
中科院分区:
--
文献类型:
--
作者:
Hoffmann,KJ;Baillie,TA

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Alkoxycarbonyl derivatives of the cysteine‐,N‐acetylcysteine‐ and glutathione conjugates of acetaminophen have been prepared in aqueous buffer solutions and their chromatographic and mass spectrometric properties examined. Structurally informative fragmentation patterns of the cysteine‐ andN‐acetylcysteine derivatives were obtained when their methyl esters were subjected to analysis by direct insertion chemical ionization (CH4) mass spectrometry, although field desorption and liquid secondary ion mass spectrometric techniques were required in order to obtain satisfactory spectral data for derivatives of the glutathione adduct. Treatment of ethoxycarbonyl derivatives of the three acetaminophen metabolites withN‐methyltrifluoroacetamide‐based silylating reagents led to the formation of a common volatile product which was ideally suited to analysis by gas chromatography/electron impact mass spectrometry. A mechanism is proposed for the formation of this novel derivative, which appears to possess a benzo‐1,3‐thioxalane structure, and its mass spectral characteristics are reported. Finally, the utility of alkoxycarbonyl derivatives for the analysis of drug—thioether conjugates in biological fluids is discussed in terms of their advantages for aqueous phase derivatization, purification by high‐performance liquid chromatography and characterization by mass spectrometry.
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