Forensic and Chemical Warfare Toxicology

NMR is not widely used in forensic toxicology, probably due to the perceived poor sensitivity and the lack of routine access to high-field (>500 MHz) NMR instrumentation. Some interesting historical examples using low-field magnets demonstrate the versatility of NMR for identifying biomarkers of poisoning. Cartigny and colleagues [36] reported on a 4-month-old girl who presented with agitation, fever, dehydration, and metabolic acidosis. Metabolites including o-hydroxyhippuric acid, 2,5-dihy-droxyhippuric acid, and 2-hydroxybenzoic acid (salicylic acid) were observed in XH NMR spectra of freeze-dried urine, which indicated that she had been poisoned with aspirin. The pattern of unusual metabolites can provide a biomarker of aspirin poisoning. This result was remarkable in that an 80-MHz system was employed. NMR has also been used to monitor progressive liver failure following paracetamol-related overdose (10 g) [37]. In addition, the second-ever known instance of acute intentional tetrahydrofuran poisoning was also investigated by NMR ofuntreated urine and serum samples, and the results were confirmed by using GC-MS [38]. Poisonings with the herbicide paraquat were revealed by analyzing untreated urine samples using NMR [39]. The latter studies used 300-MHz NMR systems, which proves that useful evidence has been derived in poisoning cases even with routinely available instruments. However, for more subtle poisonings, higher field strengths would surely provide greater sensitivity and resolution. Another forensic investigation used a 200-MHz system to investigate the value of NMR in quantifying multiple components of saliva, including ethanol, as a direct measure of alcohol consumption [40].

An example from the drug-doping arena is a report on the use of 1H NMR for measuring creatine in urine samples as a biomarker for the use ofillegal dietary supplements by French athletes [41]. Creatine is not typically measured in clinical laboratories, and common methods such as LC-MS and capillary electrophoresis require much sample preparation. The detection limits by NMR were 1.31 mg L-1, and the analysis of untreated urine samples took less than 10 min. Although forensic toxicology reports are scarce, it is evident that some forensic laboratories have access to conventional NMR systems.

In the field of warfare intelligence, preliminary results were recently reported from an integrated genomics, proteomics, and metabonomics approach to studying the toxicity of chemical warfare agents (CWAs) [42]. The toxicity of vesicant sulphur mustard (HD) in minipigs was investigated by Dillmann and colleagues with the goal of identifying exposure biomarkers, carrying out advanced drug development, validating models, and studying interspecies differences. Dose- and time-related urinary profiles were measured by NMR at 600 MHz, and thiodiglycol was identified as a metabolic marker of HD exposure. In addition, an N-acetylated cysteinyl sulphur mustard conjugate was also clearly observed. In these studies, it is clear that NMR provided valuable data with minimal sample preparation, without the need to preselect analytes for detection, and without the need to develop chromatographic techniques.

Application of newer NMR technologies in forensic toxicology has yet to be reported, but with the advancing NMR sensitivity described in Section 8.5 this is likely to change over the coming decade. Flow-injection NMR can be enabled on NMR systems of 300 MHz and higher. The INCA system (Section 8.5.2), which has minimal requirements for laboratory space and operator skill, will see increasing use in clinical laboratories. A conventional NMR system of 400 MHz and higher can also be upgraded by addition of an LC and MS system for analyzing drugs and metabolites in complex mixtures by LC-NMR-MS. Finally, the exploratory power of HRMAS for tissue analysis may be of value in autopsies and time-of-death studies.

0 0

Post a comment