Methyl isocyanate metabolites

Guest, I., Varma, D.R. (1994). Inhibition of mouse embryonic, yolk sac, and limb-bud functions by the methyl isocyanate metabolite S-(N-methylcarbamoyl) glutathione. Can. J. Physiol. Pharmacol. IT 50-6. 

Many organic chemicals are analyzed by RPC. These include various arylhydroxylamines as the N-hydroxyurea derivative with methyl isocyanate (614) alkyl- and alkoxy-disubstituted azoxybenzenes (6t5), n-alkyl-4-nitrophenylcarbonate esters ranging in length from methyl to octyl (616), 4-nitrophenol in the presence of 4-nitrophenyl phosphate (617), ben-zilic acid, and benactyzine-HCI using ion-pair chromatography (618), as well as aniline and its various metabolites (619), stereoisomers of 4,4 -dihydroxyhydrobenzoin (620), and aldehydes and ketones as the 2,4-dinitrophenylhydrazones (621). The technique has also been used to analyze propellants and hydrazine and 1,1-dimethylhydrazine were quantitita-vely determined (622, 623). 

Physicochemical Reactions with MIC MIC can interact with a large number of molecules as well as with itself Indeed, 21 identified (Varadarajan et al., 1985) and almost ten unidentified chemicals (Sriramachari, 2004) were detected in the culprit MIC Tank E-610. An MIC trimer as well as other metabolites of MIC such as dimethyl isocyanurate and 2,4-dione of methyl isocyanate were identified in autopsy samples from Bhopal victims (Chandra et al, 1991, 1994 Saraf et al, 1995). Reaction of MIC with water is important because this will occur whenever MIC comes into contact with a body or environment, as happened in Bhopal. It is important to note that while excess water can neutralize MIC, a small quantity of water is sufficient to generate heat during the reaction, which would lead to vaporization of MIC, as actually happened in Bhopal. Some important interactions of MIC are enumerated below ... 

In APCI mass spectra of carbamates, fragment ions are observed, which are most likely due to thermal decomposition in the heated nebulizer interface and snbseqnent ionization of the thermal decomposition products [11, 14, 20-23]. For example, base peaks were observed at m/z 163 for oxamyl, due to the loss of methyl isocyanate, at m/z 168 for propoxur, dne to the loss of propylene, and at m/z 157 for aldicarb, due to the loss of HjS. The APCI mass spectra of aldicaib and two of its metabolites, aldicarb sulfoxide and aldicarb snlfone, showed significant fragmentation. Major fragments for aldicarb were dne to the loss of carbamic acid (to m/z 116) and due to charge retention at [CH3-S-C(CH3)2]. For aldicarb sulfoxide and aldicarb sulfone, the loss of carbamic acid resnlted in the base peaks of the spectra (at m/z 132 and 148, respectively). 

Pearson PG, Slatter JG, Rashed MS, et al. (1990) S-(N-methylcarbamoyhglutathione A reactive S-linked metabolite of methyl isocyanate. Biochemical and Biophysical Research Communications 166 245-250. 

Dehydroabietyl isocyanate, [39], was used by Falck et al. to determine the absolute configuration of hydroxyeicosatetraenoic acid methyl esters in a study of the enzymatic epoxidahon of arachidonic acid (175). In another study of similar metabolites, the stereochemical identity of 12-hydroxy-5,8,10,14-eicosatetraenoic acid derived from the lesional scale of patients with psoriasis was studied via separation of the enantiomers after derivatization with [39] (176). In these studies (175,176), LC separation of the derivatives was used. CDA [39] can be prepared from commercially available resolved dehydroabietylamine. It would be worthwhile to examine the applicability of this CDA to the resolution of other compounds. 

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