Black R M, Hambrook J L, Howells D J, Read R W
Chemical and Biological Defence Establishment, Salisbury, Wiltshire, United Kingdom.
J Anal Toxicol. 1992 Mar-Apr;16(2):79-84. doi: 10.1093/jat/16.2.79.
The urinary excretion profiles of some metabolites of sulfur mustard were determined by gas chromatography/mass spectrometry after cutaneous application of sulfur mustard in rats. Excretion profiles of the individual metabolites thiodiglycol and thiodiglycol sulfoxide, derived from the hydrolysis of sulfur mustard, were determined in different groups of three rats. Concentrations of thiodiglycol detected increased up to 10 fold after treatment of the urine with hydrochloric acid, presumably because of the excretion of acid-labile esters of thiodiglycol. Free thiodiglycol, free plus esterified thiodiglycol, and thiodiglycol sulfoxide excreted over 8 days accounted for less than 0.3%, 1-1.5%, and 3.4-4.3%, respectively, of the applied dose of sulfur mustard. In a further study, a modified analytical method was applied to determine these hydrolysis products and their acid-labile esters as the single analyte thiodiglycol, after treatment with acidic titanium trichloride. The excretion profile of the combined hydrolysis products was compared with the excretion profile of a different group of metabolites of sulfur mustard derived from the glutathione/beta-lyase pathway. These were also reduced to a common analyte, 1,1'-sulfonylbis-[2-(methylthio)ethane], after similar treatment with titanium trichloride. Urinary excretion of hydrolysis products determined in 4 rats over 8 days accounted for 3.7-13.6% of an applied cutaneous dose of sulfur mustard. Urinary excretion of beta-lyase metabolites accounted for 2.5-5.3% of the applied dose in the same group of rats. The excretion of beta-lyase products showed a much sharper decline than was observed for the hydrolysis products of sulfur mustard.
在大鼠皮肤涂抹芥子气后，通过气相色谱/质谱法测定了芥子气某些代谢产物的尿排泄情况。在三组不同的大鼠中，测定了芥子气水解产生的单个代谢产物硫二甘醇和硫二甘醇亚砜的排泄情况。用盐酸处理尿液后，检测到的硫二甘醇浓度增加了高达10倍，这可能是由于硫二甘醇的酸不稳定酯的排泄。在8天内排泄的游离硫二甘醇、游离加酯化硫二甘醇和硫二甘醇亚砜分别占涂抹芥子气剂量的不到0.3%、1 - 1.5%和3.4 - 4.3%。在进一步的研究中，应用了一种改进的分析方法，在用酸性三氯化钛处理后，将这些水解产物及其酸不稳定酯作为单一分析物硫二甘醇进行测定。将合并的水解产物的排泄情况与另一组来自谷胱甘肽/β-裂解酶途径的芥子气代谢产物的排泄情况进行了比较。在用三氯化钛进行类似处理后，这些产物也被还原为一种共同的分析物1,1'-磺酰基双-[2-(甲硫基)乙烷]。在4只大鼠中，8天内测定的水解产物的尿排泄量占皮肤涂抹芥子气剂量 的3.7 - 13.6%。在同一组大鼠中，β-裂解酶代谢产物的尿排泄量占涂抹剂量的2.5 - 5.3%。与芥子气的水解产物相比，β-裂解酶产物的排泄下降得更为明显。
