Atmospheric pressure ionization tandem mass spectra of protonated timolol

Abstract

Structural identification of drugs by tandem mass spectrometry (MS/MS) is interesting, important and challenging. In this study, atmospheric pressure ionization (API) MS/MS was applied to probe the structure of timolol, a typical β-adrenergic receptor-blocking agent (β-blocker). The characteristic MS/MS features of this drug were analyzed in detail. The results should be significant for other β-blockers with similar structures (namely, the OCH2 group sandwiched between the aromatic and ethanolamine groups). Furthermore, timolol is a multifunctional organic compound, containing amine, ether and alcohol functional groups. The API-MS/MS study is interesting from the point of view of the gas-phase chemistry of these groups in a multifunctional compound. The results revealed that under the collision-induced dissociation conditions used for the MS/MS study, protonated timolol undergoes heterolytic, charge-induced cleavages of the amine nitrogen–carbon and ether oxygen–carbon bonds. The mechanism of the cleavages was elucidated by comparing the tandem mass spectra of timolol with those of deuterated timolol. This comparison clearly indicated that ion–neutral complexes are intermediates in the cleavages. Copyright © 1999 John Wiley & Sons, Ltd.