Potential neurotoxicity of NaBH4 reduced paraquat.

Paraquat [(2 MP*), 1,l '-dimethyl-4,4'-bipyridine dication] is a herbicide used for weed control in various crops or for desiccation of marihuana plants. Accidental and suicidal poisonings with paraquat are not uncommon (1). Several analytical methods have been published for the determination of 2 MP' in human body fluids, postmortem tissues, air, and foods consumed by humans. Analysis of 2 MP' in these samples often involves reduction of 2 MP* to a diene derivative [(4 '-bipyridine] using NaBH, (2-6). Recently Javitch et al. (7) reported that l-methyl-4-phenyl-l,2,3,6-tetraphydropyridine (MPTP), a byproduct of the opiate meperidine, produces neuropathological and clinical abnormalities in humans that closely resemble idiopathic parkinsonism. MPTP produces apparently irreversible symptoms by active accumulation of its oxidized derivative l-methyl-4-phenylpyridine monocation (MPP'). MPP + was also developed as a selective herbicide cyperquat but was never marketed (8). It accumulates in striatal and cerebral cortical synaptosomes binding to dopaminergic neuron receptor sites to levels several thousand fold above extracellular concentration (7 and references therein). The neurological syndrome produced in man is similar in clinical, pathological, neurochemical, and pharmacological response properties to idiopathic Parkinson's disease (9). Recently, it was reported (10) that a chemist involved in the synthesis of MPTP developed Parkinson's disease, probably due to adventitous exposure to MPTP (e.g., cutaneous contact or inhalation). Since the methodology described above, for the analysis of 2 MP+, requires synthesis of the MPTP analog, 2 MTP, in sufficient quantities (0.1 to 1 g) to isolate as a primary standard, the safety concern is obvious. 2 MTP is prepared to make it volatile for gas-liquid chromatographic (GLC) analysis. Contact by inhalation may present a hazard during concentration under vacuum or from GLC effluents, as well as other handling procedures. 2 MTP may be potentially neurotoxic, with clinical evidence of idiopathic parkinsonism, only after a delayed period requiring accumulation to a threshold dose. Since the time required for this depends upon the potential potency of 2 MTP, route of exposure, concentration or dose exposed to, age (11), and genetic predisposition (11), analysts should be aware of the potential neurotoxicological hazard of reduced paraquat (2 MTP). A rapid and sensitive method for the determination of paraquat in plasma by gas-liquid chromatography. A rapid method for the analysis of diquat and paraquat in potatoes. and analysis of airborne residues of paraquat in treated cotton field environments. Quantitative determination of the herbicide paraquat in human plasma by gas chromatographic mass spectrometric …