Abstract
A systematic mass spectrometric study of 10 thiazidic diuretics and related compounds was undertaken by mass spectrometry (MS) with electrospray ionization in the negative ion mode. Collisional dissociation ‘in‐source’ (CID‐MS) and in a low‐pressure collision cell (CID‐MS/MS) were compared in both excitation regions. Spectra obtained by CID‐MS and by CID‐MS/MS were matched. Using the two methods, loss of HCl and consecutive dissociations from 2HCl losses were exhibited from compounds such as methyclothiazide and trichlormethiazide but not from other thiazidic diuretics that contain chlorine substituents in the aromatic moiety. However, deprotonated dichlorphenamide gave rise to loss of HCl by CID‐MS and CID‐MS/MS. For other diuretics such as hydroflumethiazide and hydrochlorothiazide, the loss of HCN and [HCN + SO~2~] was relevant. Reaction mechanisms were checked by means of deuterium–hydrogen exchange, which showed that deprotonation took place regioselectively on the heterocyclic moiety. The cleavage pathways require molecular isomerization forming ion–dipole complexes prior to decompositions, allowing long‐distance proton transfer for neutral elimination. Identifications of the most specific fragmentations presented in this paper were applied to the screening and unambiguous identification of diuretics for horse doping control. Copyright © 2002 John Wiley & Sons, Ltd.