Mass Spectrometric Study of a Specific Derivatization Reaction BetweenN,N-Dimethylformamide Dimethylacetal and the Ethanolamine Moiety of β-Agonistic Drugs
✍ Scribed by Montrade, M.-P.; Maume, D.; Le Bizec, B.; Pouponneau, K.; Andre, F.
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 996 KB
- Volume
- 32
- Category
- Article
- ISSN
- 1076-5174
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✦ Synopsis
In a study designed to examine the nature of a speciÐc reaction which was shown to occur between the ethanolamine moiety of b-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 Á 10 000) and linked-scan experiments performed on reverse-geometry doublefocusing mass spectrometers were helpful to conÐrm structural hypotheses. From this study, it appeared that the secondary amine of the ethanolamine group of b-agonists can react with DMF-DMA (DMA being the active part of the reagent) to give mainly an ethanolamide intermediate. Apart from this ethanolamide intermediate, three reaction products which are partly due to a dehydration step of the ethanolamide that occurs at high temperatures were identiÐed. 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 Ðndings may be of great help for the survey of b-agonist residues. Actually, the above-mentioned reaction products could be easily detected and identiÐed in biological samples by means of gas chromatography (Ross injector, 280 ÄC) 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 identiÐcation of new analogues. On the other hand, the analysis of ethanolamide intermediates via liquid or thinlayer chromatography coupled to FABMS would also appear to o †er valuable analytical solutions.