Monitoring Urine Thiodiglycol after Rabbit Skin Exposure to Sulfur Mustard Based on Highly-sensitive Isotope Dilution Gas Chromatography-Mass Spectrometry
A sensitive determination method for sulfur mustard( HD) metabolites thiodiglycol( TDG) in rabbit urine was established and validated using isotope dilution negative ion chemical ionization( NICI) gas chromatography-mass spectrometry( GC-MS),in which deuterated thiodiglycol( TDG-d8) was used as internal standard. Two solid-phase extraction( SPE) steps were established and optimized in order to reduce the interfering backgrounds,one was used to extract thiodiglycol( TDG) from urine with self-assemblied Florisil SPE cartridges, another cleaning treatment of the by-products after pentafluorobenzoyl chloride( PFBZ) derivatization. The results showed that the limits of detection quantitation of this method were 0. 1and 0. 3 μg /L,respectively. The exposure time-response relationship and exposure dose-response relationship of TDG in rabbit urine were studied after rabbit skin exposure to sulfur mustard( HD,0. 02-0. 15 LD50). The TDG levels in the rabbit urine increased rapidly during the first day after application and then decreased over time for all dosage groups. A secondary release was also noted for the high-dose group,and the duration of high TDG excretion levels was correlated positively with the HD dosage levels. We thus concluded that abnormally high levels of TDG in urine could be used as a clear diagnostic indicator of HD exposure.