Ultraviolet photodissociation facilitates mass spectrometry-based structure elucidation with pyrrolidine and piperidine containing compounds.

Autor: Chen B; Small Molecule Pharmaceutical Sciences, Genentech Inc., South San Francisco, CA 94080, United States., Kurita KL; Small Molecule Pharmaceutical Sciences, Genentech Inc., South San Francisco, CA 94080, United States., Wong N; Small Molecule Pharmaceutical Sciences, Genentech Inc., South San Francisco, CA 94080, United States., Crittenden CM; Small Molecule Pharmaceutical Sciences, Genentech Inc., South San Francisco, CA 94080, United States. Electronic address: crittenden.christopher@gene.com.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2022 Mar 20; Vol. 211, pp. 114622. Date of Electronic Publication: 2022 Jan 26.
DOI: 10.1016/j.jpba.2022.114622
Abstrakt: In pharmaceutical development, structural elucidation of small molecules from process related impurities and degradation products is an essential component. As one of the most important methods in the toolbox, high resolution mass spectrometry (HRMS) and specifically tandem mass spectrometry (MS/MS) often provide fast and informative structural insights. However, many small molecule drugs containing certain biological relevant pharmacophores result in limited numbers of fragments when using traditional collision based fragmentation techniques, such as higher energy collisional dissociation (HCD), due to its inherent preference of cleaving the weakest bond first. As an alternative, ultraviolet photodissociation (UVPD), which irradiates the precursor ion with high energy photons, can lead to more extensive fragmentation from the readily UV absorbing small molecules. Here, we showcase the advantage of UVPD over HCD on pyrrolidine and piperidine containing molecules derivatized from a model compound, telmisartan. While HCD only yielded a single, highly abundant ion resulting from the pyrrolidine and pipieridine ring cleavage, UVPD generated rich and structurally informative fragment ions. UVPD is an attractive and powerful alternative for traditional fragmentation techniques for small molecule structural elucidation.
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Databáze: MEDLINE
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