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Abstract
Self-poisoning with professional agricultural pesticide products is responsible for about 20% of global suicide, with most cases occurring in South Asia and China. Treatment of severe poisoning involves long-term intensive clinical care and is often unsuccessful. Solvent co-formulants (such as cyclohexanone) also contribute to mortality themselves or via more toxic metabolic products (such as cyclohexanol). Faster detection of co-formulants could aid earlier identification of pesticide poisoning and faster intervention, reducing mortality. Conventional analysis of volatiles in blood uses headspace (HS)-GC/MS. This paper evaluates SIFT-MS, a direct MS technique that provides higher sample throughput than GC/MS, as a potential tool for cyclohexanone and cyclohexanol analysis in plasma. Both instruments were calibrated using a conventional approach prior to analysis of each porcine plasma sample on both instruments. Comparative data were evaluated using Bland–Altman plots, demonstrating that the techniques were in good agreement. Compared with GC/MS, SIFT-MS provides fourfold higher sample throughput and shows great promise as an alternative analytical tool.
Highlights
Self-poisoning with professional agricultural pesticide products is responsible for about 20% of global suicide, with most cases occurring in South Asia and China.[1,2]
The detection of volatile substances such as ethanol[9] and isoflurane[10] in blood is enabled by headspace-gas chromatography/mass spectrometry (HS-GC/ mass spectrometric (MS)), and this approach can be applied to the measurement of volatile cyclohexanone and its metabolite cyclohexanol
Calibration plots are shown for selected ion flow tube-mass spectrometry (SIFT-MS) (Figure 1) and for GC/MS (Figure 2)
Summary
Self-poisoning with professional agricultural pesticide products is responsible for about 20% of global suicide, with most cases occurring in South Asia and China.[1,2] Treatment of severe poisoning involves long-term intensive clinical care and is often unsuccessful.[3−5] Harm following ingestion is caused by the pesticide itself and, in some cases, by solvent coformulants such as cyclohexanone.[6,7] The samples reported here were collected from an ongoing preclinical study to investigate the effects of organophosphorus pesticides and the solvent cyclohexanone (which is metabolized to the more toxic cyclohexanol) on neuromuscular function in terminally anaesthetized pigs. To understand the concentration−effect relationship, we sought to measure the concentration of both cyclohexanol and cyclohexanone in plasma. Current gold standard targeted analytical methods for simultaneous analysis of small molecules and their metabolites, such as steroids, use mass spectrometry coupled to liquid or gas chromatography.[8] The detection of volatile substances such as ethanol[9] and isoflurane[10] in blood is enabled by headspace-gas chromatography/mass spectrometry (HS-GC/ MS), and this approach can be applied to the measurement of volatile cyclohexanone and its metabolite cyclohexanol
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