1H NMR spectroscopy and GC-MS analysis of alpha-chloralose. Application to two poisoning cases.

Alpha-chloralose, a compound widely used as a rodenticide and in the control of bird pests, is readily available. Two cases of intentional poisoning are reported. Both patients became comatose and presented hypersialorrhea and myoclonal crises in the legs. They were discharged from hospital after several days. As clinical signs of alpha-chloralose poisoning lack specificity, anamnesis might be difficult, particularly in the case of delayed diagnosis. Toxicological analysis is therefore critical, and this article reports the investigation of serum and urine samples by gas chromatography-mass spectrometry (GC-MS) in the electron-impact mode, and by 1H nuclear magnetic resonance (1H NMR) spectroscopy. Non-hydrolyzed urinary samples and those hydrolyzed by beta-glucuronidase were taken into consideration. After acetylation, GC-MS analysis was based on characteristic mass-to-charge ratio values of 272 for alpha-chloralose and 206 for beta-hydroxyethyltheophylline, which was used as internal standard. Characterization of alpha-chloralose species by 1H NMR spectroscopy was performed taking two parameters into account: chemical shift and coupling-constant values. Without any pretreatment, 1H NMR spectroscopy revealed the presence of free (5.50 and 6.15 ppm) and conjugated forms of alpha-chloralose by characteristic resonances of H1 and chloral-type protons, respectively. Quantitative analysis was performed by relative integration of peak areas. Serum alpha-chloralose showed concentrations below the quantitation limit of both methods. In urine samples, the free chemical species rapidly decreased. GC-MS analysis revealed the predominence of conjugation after a beta-glucuronidase hydrolysis step. 1H NMR analysis directly showed that on admission of the first patient, average urinary concentrations were 1.73 mmol/L (535 mg/L) for the free form and 13.72 and 6.25 mmol/L for the two conjugated forms. A later enzymatic treatment confirmed the total concentration of alpha-chloralose chemical species. Analysis of alpha-chloralose in urine by either GC-MS or 1H NMR spectroscopy methods proved to be comparable.

The toxic effects of alpha-chloralose.

1. Alpha-chloralose, formed by the condensation of glucose with chloral, is used as a rodenticide and in the control of bird pests. 2. In two cases of poisoning with alpha-chloralose the clinical features included coma and generalized convulsions resembling the effects of strychnine more than those of chloral hydrate. 3. The principles of management are the support of vital functions in the unconscious patient and removal of unabsorbed poison by gastric lavage. Diazepam may be used to control convulsions.

[Toxicologic analysis of chloralose. Application to 3 cases of acute intoxication]. / Toxicologie analytique du chloralose. Application dans 3 cas d'intoxication aiguë

The authors describe the study of three human intoxication case by chloralose. The detection and dosage of the toxic in the urine of patients have been carried out by the mean of a technic perfected by the same authors. In two case, it has been possible to trace the elimination of the toxic in the urine, the data relative to the third case were not sufficiently precised but they enable to show the existence of criminal etiology of chloralose.