Beta- 2 agonists are a class of compounds that are used to treat asthma, chronic obstructive pulmonary disease, and other respiratory diseases; however, these same drugs have also been shown to have potential for abuse as performance-enhancing drugs (PEDs) and are thus regulated under anti-doping initiatives. Beta- 2 agonists are well studied in the context of their pharmacology, prevalence in wastewater, and similar. To those ends, several detection and quantitation methods have been developed, including several on LC-MS/MS platforms. Despite the widespread reliance on MS/MS dissociation patterns, in-depth fundamental studies of such are largely lacking, despite an acknowledged need for better understanding of class-wide behaviors and themes.<br/>The current work, a portion of which has recently been submitted for publication, to be presented here focuses on reporting the energy-resolved CID-MS of salbutamol, formoterol, salmeterol, and isoetharine. After neutral losses are assigned based on the experimental data, relative thermodynamics of hypothetical reaction pathways to facilitate such neutral losses are explored using computational chemistry. CID-MS experiments were carried out on a Bruker microTOF-Q II, with an electrospray ionization source. Computational chemistry was performed using density functional theory at the B3LYP/6-311++G** level.<br/>Our experimental results show that water loss is a common first dissociation step for all four beta- 2 agonists studied; further, subsequent second water loss is observed (where applicable) as a second step or further down the dissociation channel. Additionally, cleavage at heteroatoms was a common motif, most prevalent at the nitrogen of the characteristic ethanolamine sidechain of beta- 2 agonists. Notably, the thermodynamic results challenge previously reported structures from the literature for albuterol. Proposed dissociation pathways, other pathways considered, and theoretical thermodynamics will be discussed for all four investigated beta-2 agonists and an update on ongoing experiments will be provided. Ongoing work aims to determine whether the thermodynamically preferred pathways are those that actually occur within the mass spectrometer’s environment.

Characterization of the gas-phase dissociation pathways of beta- 2 agonists: Insights from experiment and theory

ACS Spring Meeting 2021

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