Gas-phase dissociation pathways of Beta-2 agonists

Beta-2 agonists are widely used for the treatment of asthma and other respiratory conditions. These same drugs, however, may also be taken with the aim of gaining an unfair advantage in sports competition, thus they are controlled under anti-doping initiatives. While there are several analytical protocols relying on MS/MS to identify various molecules in this class, relatively little work has been done on unraveling the underlying gas-phase dissociation chemistry for this class of molecules. Here, we apply collision-induced dissociation mass spectrometry (CID-MS) to a group of beta-2 agonists to explore characteristic dissociation pathways and we perform complementary density functional theory calcu-lations to better understand the underlying chemistry and the associated theoretical thermodynamics. Common dissociation pathways include one or more losses of water, and cleavage at the amine nitrogen is common, sometimes with the observance of complementary charge-retention pairs. In the case of more complex molecules, additional losses are observed, which lend insights into their specific struc-tures. These various pathways are discussed in detail for protonated isoetharine, salbutamol, formoterol, and salmeterol. The goal of this work is to contribute to a foundation of knowledge on the dissociation pathways of pharmaceuticals, especially those regulated as performance enhancing drugs. (c) 2021 Elsevier B.V. All rights reserved.