title: Gas-phase behaviour of negative ions produced from thiazidic diuretics under electrospray conditions.
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.
authors.affiliation: L.A.B./F.N.C.F., 169 Avenue de la Division Leclerc, 92290 Châtenay-Malabry, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Garcia
authors.forename: Marie Agnès
authors.initials: MA
authors.lastname: Popot
authors.forename: Françoise
authors.initials: F
authors.lastname: Fournier
authors.forename: Yves
authors.initials: Y
authors.lastname: Bonnaire
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Tabet
mesh_terms: D001581:Benzothiadiazines; D002851:Chromatography, High Pressure Liquid; D004232:Diuretics; D005740:Gases / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents; D049993:Sodium Chloride Symporter Inhibitors / Q000032:analysis* / Q000652:urine; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D001581:Benzothiadiazines; D004232:Diuretics; D005740:Gases; D007202:Indicators and Reagents; D049993:Sodium Chloride Symporter Inhibitors