Mass Spectrometric Study of a Specific Derivatization Reaction BetweenN,N-Dimethylformamide Dimethylacetal and the Ethanolamine Moiety of β-Agonistic Drugs

• Published in: Journal of mass spectrometry. 1997-06, Vol.32 (6), p.626-644
• Main Authors: Montrade, M.-P., Maume, D., Le Bizec, B., Pouponneau, K., Andre, F.
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Chemical Sciences; Life Sciences; Santé publique et épidémiologie
• ISSN: 1076-5174; 1096-9888
• DOI: 10.1002/(SICI)1096-9888(199706)32:6<626::AID-JMS517>3.0.CO;2-R

In a study designed to examine the nature of a specific reaction which was shown to occur between the ethanolamine moiety of beta-agonists and N,N-dimethylformamide dimethylacetal (DMF-DMA), several mass spectrometric techniques were used to identify the main reaction intermediates and/or products. In particular, the use of fast atom bombardment (FAB) ionization made the study of polar and thermosensitive low molecular mass compounds possible. High-resolution (R approximate to 10000) and linked-scan experiments performed on reverse-geometry double-focusing mass spectrometers were helpful to confirm structural hypotheses. From this study, it appeared that the secondary amine of the ethanolamine group of beta-agonists can react with DMF-DMA (DMA being the active part of the reagent) to give mainly and ethanolamide intermediate. Apart from the ethanolamide intermediate, three reaction products which are partly due to a dehydration step of the ethanolamide that occurs at high temperatures were identified. Two of them are the results of a cleavage of the side-chain which gives a styrene and an isocyanate derivative; the third one corresponds to an azetidine derivative stemming from a side-chain cyclization. These unexpected findings may be of great help for the survey of beta-agonist residues. Actually, the above-mentioned reaction products could be easily detected and identified in biological samples by means of gas chromatography (Ross injector, 280 degrees C) coupled to mass spectrometry (GC/MS); the side-chain cleavage observed during the formation of the styrene and isocyanate derivatives was useful to broaden the range of detection and to facilitate the identification of new analogues. On the other hand, the analysis of ethanolamide intermediated via liquid of thin-layer chromatography coupled to FABMS would also appear to offer valuable analytical solutions.