MASS-SPECTROMETRIC STUDY OF A SPECIFIC DERIVATIZATION REACTION BETWEEN N,N-DIMETHYLFORMAMIDE DIMETHYLACETAL AND THE ETHANOLAMINE MOIETY OF BETA-AGONISTIC DRUGS

In a study designed to examine the nature of a specific reaction which was shown to occur between the ethanolamine moiety of beta-agonists a nd N,N-dimethylformamide dimethylacetal (DMF-DMA), several mass spectr ometric techniques were used to identify the main reaction intermediat es and/or products. In particular, the use of fast atom bombardment (F AB) ionization made the study of polar and thermosensitive low molecul ar mass compounds possible. High-resolution (R approximate to 10000) a nd linked-scan experiments performed on reverse-geometry double-focusi ng mass spectrometers were helpful to confirm structural hypotheses. F rom this study, it appeared that the secondary amine of the ethanolami ne group of beta-agonists can react with DMF-DMA (DMA being the active part of the reagent) to give mainly and ethanolamide intermediate. Ap art from the ethanolamide intermediate, three reaction products which are partly due to a dehydration step of the ethanolamide that occurs a t high temperatures were identified. Two of them are the results of a cleavage of the side-chain which gives a styrene and an isocyanate der ivative; the third one corresponds to an azetidine derivative stemming from a side-chain cyclization. These unexpected findings may be of gr eat 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 cleav age observed during the formation of the styrene and isocyanate deriva tives was useful to broaden the range of detection and to facilitate t he identification of new analogues. On the other hand, the analysis of ethanolamide intermediated via liquid of thin-layer chromatography co upled to FABMS would also appear to offer valuable analytical solution s.