Vanadium Pentoxide–Mediated Oxidation Coupled with HPLC-MS/MS for Broad-Spectrum Screening of Paralytic Shellfish Toxins in Plasma

Paralytic shellfish toxins (PSTs), potent neurotoxic alkaloids produced by marine dinoflagellates and cyanobacteria, pose severe risks to human health through contaminated seafood and water after absorption into the bloodstream. Current detection methods are limited by matrix interference or ethical concerns. Here, we report a novel screening approach using vanadium pentoxide as an oxidant to convert PSTs into characteristic oxidation products, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC‒MS/MS) analysis. Under optimized conditions, vanadium pentoxide oxidizes both hydroxylated and non-hydroxylated toxins into distinct major products (P1‒P7), identified by high-performance liquid chromatography‒tandem high-resolution mass spectrometry (HPLC‒HRMS). Vanadium pentoxide oxidation affords excellent product selectivity and, for most PSTs, superior signal intensities, enabling unambiguous differentiation of toxin subgroups. HPLC‒MS/MS method in MRM mode was developed and yielded detection limits of 0.3‒1.5 ng/mL for a broad spectrum of fourteen PSTs in spiked plasma, accuracy of 89.3‒102.2%, and excellent repeatability with intra- and inter-day relative standard deviations (RSDs) ranging from 0.3% to 10.4%. Application of the method to samples from the First Trial OPCW (the Organisation for the Prohibition of Chemical Weapons) Biotoxin Proficiency Test successfully identified STX/neoSTX, confirming its practical utility for trace PSTs detection in complex biological matrices.