Degradation of the tricyclic antipsychotic drug chlorpromazine under environmental conditions, identification of its main aquatic biotic and abiotic transformation products by LC-MSn and their effects on environmental bacteria.

Positive secondary-ion mass spectra and thin-layer chromatography/mass spectrometry of phenothiazine drugs

The metabolic fate of chlormethiazole in healthy male subjects has been investigated following the oral administration of a single dose of chlormethiazole edisylate. Five urinary C-oxidation metabolites were identified and shown to be identical with previously reported metabolites. A novel metabolite, of molecular formula C5H7NO2S, was shown by trimethylsilylation, deuterium exchange, reduction studies and by its i.r., n.m.r. and mass spectrum, to be 4,5-dimethylthiazole-N-oxide-S-oxide. This is the first reported metabolite which involves the oxidation of the two heterocyclic atoms in aromatic rings. The formation and thermal stability of the compound is ascribed to resonance stabilization.

4,5-Dimethylthiazole-N-oxide-S-oxide: a metabolite of chlormethiazole in man

The mass spectral behavior of a set of eight 2- and 10-disubstituted phenoxazines putatively possessing anticancer drug enhancer properties was investigated. Both electron ionization (EI) and keV-ion beam bombardment (liquid secondary ion mass spectrometry, LSIMS) were used. As expected, EI led to extensive fragmentation to produce structurally characteristics ions. Except in one example, the molecular ions were reasonably abundant. Two different liquid matrices--sulfolane and 3-nitrobenzyl alcohol--were used to obtain LSIMS data. The use of the latter produced more stable molecular ions. Ion beam bombardment also produced several structure-specific fragments. A unique feature of the LSI spectra obtained using either of the above matrices is production of both M+. and [M + H]+ ions, with the former being more abundant in most cases. Adduct formation with the liquid matrices was also observed for many compounds.

Analysis of phenoxazine chemosensitizers: An electron ionization and keV‐ion beam bombardment mass spectrometry study

Positive ion methane and ammonia chemical ionization mass spectra for ten phenothiazine derivatives are reported. The fragmentations observed in the chemical ionization mass spectra are rationalized in terms of the location of the added proton. High-resolution measurements are used to confirm empirical formulae of the ions in the mass spectra. Changes in the mass spectra with a change in the chemical ionization reagent gas from methane to ammonia are described. A comparison with positive ion secondary ion mass spectra of the same compounds show that the amount of fragmentation is higher in the secondary ion mass spectra, but the same types of ions are observed in spectra produced by both ionization methods.

Sites of protonation in phenothiazines: methane and ammonia chemical ionization mass spectra

The fragmentation of six substituted 10-alkylphenothiazines is discussed. Predominant expulsion of OH, SO and O occurs from the molecular ions of 10-alkylphenothiazine-5-oxide derivatives, the relative extent depending upon the configuration of the 10-substituent. The simultaneous elimination of two OH radicals from the molecular ion of 10-alkylphenothiazine-5-sulphone derivative is also observed.

The mass spectrometry of phenothiazines—I. 10‐alkylphenothiazines

The electron ionization (EI) mass spectra and the daughter-ion spectra of the EI-generated main fragments of phenothiazine S-oxides and its two N-substituted derivatives have been studied by means of ion-trap mass spectrometry (ITMS). Interesting differences with the data already published on the same molecules as obtained by a magnetic sector instrument have been rationalized by considering how, under ITMS conditions, charge exchange or self-chemical-ionization phenomena can take place, leading to molecular species with low energy content.

An ion‐trap mass spectrometric study on electron impact and collisionally induced decomposition pathways of some phenothiazine S‐oxides

Behaviour of Schiff bases derived from 10-methyl-3-amino-7-chlorophenothiazine and aromatic aldehydes under electron impact ionization

Electron ionization mass spectral behavior of N R substituted phenothiazine-S-oxides (R:CH2CCH3CH2, CH2CCH, CCCH3, COCH3, COC2H5 and COC6H5) has been studied by comparison of normal and daughter-ion mass spectra. Among several characteristic pathways, formation of [MOR]+, C12H8NS+ ions (m/z 198) was found to result in a common and abundant fragment peak for both N-alkyl and N-acyl derivatives. Appearance energy measurements as well as thermochemical considerations revealed this ˙OR loss, to be a single-step dissciation process and to correspond to the energetically most favoured primary decomposition of M+˙; it seems to involve a transannular rearrangement. The ˙OR elimination also occurred from [MH]+ ions, produced by fast-atom bombardment.

I. G. Taulov

Papers

The mass spectrometry of phenothiazines—I. 10‐alkylphenothiazines

An ion‐trap mass spectrometric study on electron impact and collisionally induced decomposition pathways of some phenothiazine S‐oxides

Behaviour of Schiff bases derived from 10-methyl-3-amino-7-chlorophenothiazine and aromatic aldehydes under electron impact ionization

An electron ionization and fast‐atom bombardment mass spectrometric study of some N(10)‐substituted phenothiazine‐S‐oxides