ArticleJournal of pharmaceutical and biomedical analysis2025
Analysis of Pz-1, a promising therapeutic for organophosphorus poisoning from rodent plasma by liquid chromatography-tandem mass spectrometry.
Article in Journal of pharmaceutical and biomedical analysis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Organophosphorus (OP) pesticides (e.g., parathion) and nerve agents (e.g., soman) can produce acute and long-term neurological problems. Exposure to OP chemicals is responsible for an estimated 200,000 deaths annually. Pz-1 (N-(5-(tert butyl)isoxazol-3-yl)-2-(4-(5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)phenyl)acetamide) is a muscle specific kinase (MuSK) inhibitor which has shown potential as a treatment for OP chemical exposure and as a tyrosine kinase inhibitor to impede the growth of cancer cells. While development of this treatment requires the availability of a validated analytical method, no method currently exists for analysis of Pz-1 from biological samples. In this study, an analytical method was developed for Pz-1 from rat (and mouse) plasma. Plasma was prepared by precipitating plasma proteins, isolating the supernatant, evaporating to dryness and reconstituting in 1:1 MeOH:water. Prepared samples were analyzed by reversed-phase liquid chromatography tandem mass-spectrometry (LC-MS/MS). The method produced excellent sensitivity, with a limit of detection of 1 nM (455 ng/L). The calibration range was 3-100 nM and the calibration curve produced excellent linear behavior (R
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