|Rapid Population Screening for Exposure to Methyl Isocyanate and Related Compounds.|
|Mon 3:30 PM - Session: Environment and Chemical Disaster|
|Methods for screening populations following large scale exposure to chemical agents must be both rapid and specific to enable clinicians to identify individuals truly exposed, as opposed to individuals from the 'worried well'. A rapid throughput method has been developed to identify the urinary glutathione metabolite marker N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urinary AMCC is a specific biomarker for methyl isocyanate (MIC) exposure.
Methyl isocyanate toxicity from the 1984 industrial accident in Bhopal, India demonstrated the potential for mass casualty from either an accidental or intentional industrial event. MIC is also a reactive metabolite of other industrial chemicals such as alkylformamides (methylformamide, dimethylformamide) as well as chemotherapeutic nitrosureas. AMCC is formed from the reaction of methyl isocyanate (MIC) with the sulfhydryl moiety of glutathione, followed by enzymatic cleavage to the cysteinyl adduct which is excreted in the urine.
In the present study, analytes were isolated from urine matrix using semi-automated 96 well solid phase extraction. The analytes were separated by reverse phase HPLC with detection by electrospray ionization tandem mass spectroscopy in the multiple-reaction-monitoring mode. Isotopic dilution was performed with a 13C- /15N-labeled analog of AMCC.
AMCC along with the isotope labeled internal standard were extracted from acidified, diluted urine using Biotage ENV+, a highly cross linked hydroxylated polystyrene polymer solid phase. Chromatographic separation by HPLC was achieved with a Phenomenex Synergi 2.5