Sulfur mustard biotransformation

TDG may undergo oxidation to TDG sulfoxide, which is conjugated with glutathione to form l,l -sulfonylbis [2-S-(N-acetylcysteinyl)ethane]. Following the p-lyase pathway, the l,l-sulphonylbis[2-(methylsulfinyl)ethane] and l-methylsulfinyl-2-[2-(methylthio)ethylsulfonyl] ethane can be formed (Black and Read, 1995). Figure 56.6 summarizes the pathways of sulfur mustard biotransformation. No sulfo- or glucuronyl-conjugates were detected in urine after i.v. administration of sulfur mustard (Maisonneuve et al., 1993). 

Vesicants, including sulfur mustard and lewisite, are the subject of the second main part of this chapter. Coherences of invasion and distribution are presented, and the major processes of biotransformation and elimination caused by binding to proteins [and more prominently, to deoxyribonucleic acid (DNA)] are discussed. Finally, we make some comments about current bioanalytical approaches. This chapter provides readers with a comprehensive overview of tire toxicokinetics of OP nerve agents and vesicants. 

Halme et al. (2011) presented a method for the efficient stable isotope dilution LC-HESI-MS/MS method for verification of p-lyase biotransformation products in human urine after sulfur mustard exposure. The p-lyase products l,l -sulfonylbis-[2-(me ylsulfinyl)ethane] (SBMSE) and l-methylsulfinyl-2-[2-(methylthio) ethyl-sulfonyl]ethane (MSMTESE) were successfully detected at a concentration of 4 ng/mL, whereas the limit of quantification was established at 10 and 11 ng/mL for SBMSE and MSMTESE, respectively. 

It is worth noting that background levels of TDG and TDG sulfoxide have been found in the urine of healthy individuals never exposed to sulfur mustard. For this reason, their validity as unambiguous markers for sulfur mustard exposure has been questioned. Black and Read (1995) suggested the determination of p-lyase pathway biotransformation products, which in the urine of exposed patients, were found at concentrations similar to those of TDG sulfoxide, but were not found in unexposed individuals. 

Li et al. (2013) presented an ultrahigh-performance LC-tandemmass spectrometry (UPLC-MS/MS) method for simultaneous quantification of seven plasma biotransformation products of sulfur mustard. Limits of quantification ranged from 0.01 to 5.0 pg/L. The main products found in rat plasma werebis-p-chloroethyl sulfoxide (SMO), TDG, TDG sulfoxide (TIX O), l,l -sulfonylbis-[2-S-(N-acetylcysteinyl) ethane] (SBSNAE), l,l -sulfonylbis-[2-(methylsulfinyl)eth-ane] (SBMSE) and l-methylsulfinyl-2-[2-(methylthio)ethyl-sulfonyl]ethane (MSMTESE). 

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