Walter Vetter

Diazepam and N-desmethyldiazepam are found in rat brain and adrenal and may be of plant origin

Benzodiazepine-binding inhibitory (BBI) activity was detected in aqueous extracts of brain and peripheral tissues of rats. The BBI activity in brain and in adrenals was, at least partially, due to the presence of N-des-methyldiazepam and diazepam as shown by HPLC, UV-spectroscopy and mass spectrometry. In addition, BBI activity was found in standardized rat food, as well as in a variety of cereals and in other nutritive plant products. In wheat grains diazepam and N-desmethyldiazepam could be identified by HPLC and analysis by gas chromatography combined with mass spectrometry. The estimated amounts of the two benzodiazepines present in rat brain and adrenals and in wheat grains were in the low ppb range. Since laboratory contamination was rigorously excluded we conclude that diazepam and N-desmethyldiazepam are naturally occurring compounds. These findings may explain their occurrence in the brain and adrenals of animals.

Occurrence of pharmacologically active benzodiazepines in trace amounts in wheat and potato

Aqueous acid extracts of wheat grains and of potato tuber were found to contain a series of compounds displaying a high affinity to the central type benzodiazepine receptor (BZR) in mammalian brain. Further analysis using different HPLC systems, as well as mass spectrometry and gas chromatography combined with mass spectrometry lead to the identification of compounds belonging to the classical 5-phenyl-1,4-benzodiazepinones. In wheat grains diazepam, N-desmethyldiazepam, delorazepam, deschloro-diazepam, delormetazepam, lormetazepam and isodiazepam were identified, while potato tuber contained diazepam, N-desmethyldiazepam, delorazepam, lorazepam and delormetazepam. The concentration of the benzodiazepines (BZ) was in the low ppb range. Their biosynthesis most probably takes place in the plant tissue. The availability of BZs in plant nutritives points to a possible source for the previously reported presence of BZ in brain and peripheral tissues of several animal species and man.

Fragmentation of Bosentan ® (Ro 47-0203) in ionspray mass spectrometry after collision-induced dissociation at low energy: a case of radical fragmentation of an even-electron ion

For metabolic studies the fragmentation of a novel endothelin receptor antagonist, Bosentan, was investigated using ionspray tandem mass spectrometry. Bosentan belongs to the sulphonamide class and a complicated and unexpected fragmentation at low energy, involving a radical fragmentation of an even-electron ion at the sulphonamide bond, is reported.

2‐Alkylimidazoline derivative to control fatty acid fragmentation upon electron impact and electrospray ionization

A new derivative of the carboxyl group, N-methyl-2-alkylimidazoline, was introduced with the aim of improving the control of fatty acid fragmentation. Owing to the strongly basic character and the cyclic structure of this derivative, strong stabilization of the charge on the ionized group is obtained so that extensive radical and charge-remote fragmentation of the chain can be achieved with electron impact and electrospray ionization.

The influence of strongly acidic groups on the protonation of peptides in electrospray MS

In order to obtain experimental data on the question of compensation of positive charges by anionic groups in multiply charged ions of polyfunctional molecules in electrospray MS, several pairs of peptides with the same basic structure but differentiated by one or two strongly acidic groups (phosphate or sulfonate) were investigated. It was found that depending on the density of basic centers and the strength of acidic groups present, the observed changes upon introduction of acidic groups ranged from complete elimination of the most highly charged state to absence of any difference.

Die Massenspektren der Pyrrolidide einiger aliphatisch-alicyclischer Carbonsäuren

The mass spectra of the pyrrolidides of some long-chain carboxylic acids with alicyclic residues attached to their ω-end are discussed and compared with the spectra of the corresponding esters. Fragmentation triggered by the pyrrolidide group generates a series of peaks, which clearly exhibits the size and the structure of the carbon chain.

Pyrrolidides as derivatives for the determination of the fatty acids of triacylglycerols by gas chromatography

Abstract Triacylglycerols can be converted quantitatively into the pyrrolidides of their constituent fatty acids. On the basis of this reaction, an easy and highly accurate gas chromatographic method for the determination of the fatty acids from triacylglycerols has been developed.