A Derivatization-Based Charge Localization Strategy for Suppressing in-Source Dehydration in LC-ESI(+)-MS Analysis of Natural Polyether Compounds

In electrospray ionization (ESI), analytes containing multiple hydroxyl or ether structures often produce multiple competing precursor ions, reducing sensitivity and complicating precursor selection. Okadaic acids (OAs) exhibited pronounced Na + /K + adduction along with sequential dehydration. In contrast, azaspiracids, which possess a secondary amine capable of forming a stable protonated species, predominantly generate [M + H] + ions. This contrast indicates that the absence of a strong charge-localization site is the dominant contributing factor under ESI conditions to ion dispersion in OAs. To address this issue, we chemically introduced a charge-localizing group via IPPAH derivatization. The resulting OAs–IPPAH derivatives exhibited substantial precursor-ion convergence in ESI(+), with up to 95% of the total ion abundance as a single [M + H] + ion. Peak intensities increased by 2.6–4.7. These findings provide the first demonstration that chemical control of charge localization can suppress in-source dehydration and metal adduct formation.