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

High Resolution Ion Mobility Enables the Structural Characterization of Atropisomers of GDC-6036, a KRAS G12C Covalent Inhibitor

“…To explain the spectral features observed in the mass spectrum for these ions in Figure d, the protonated molecular ion loses the pyrrolidine group upon ionization as an ion-source fragment and the neutral loss species is observed at m / z 525.1427 (Δ m = 0.76 ppm). Additionally, the pyrrolidine group itself is observed at m / z 98.0961 (Δ m = −3.06 ppm), a phenomenon that has been described previously for singly charged small molecules containing highly basic pyrrolidine motifs. , A description of the in-source fragments observed for GDC-6036 and Compound B are given in Figure S2. These fragment ions were mechanistically postulated through inductive cleavage and hydrogen rearrangements, aided by the use of Mass Frontier Spectral Interpretation Software (Thermo Fisher Scientific, San Jose, CA, USA).…”

“…Initial attempts at characterizing subtle differences between these two compounds from a mass spectrometry standpoint involved fragmentation efforts to reveal subtle differences in fragment ions generated. 39 However, as these compounds contain a basic pyrrolidine group derivatived to the quinazoline core, 40 the only fragment ion generated by collisional activation is associated with the pyrrolidine group itself at m/z 98.0964 (Figure S1). This presents a further need for analytical characterization and differentiation of these compounds, especially in a complex mixture.…”

Ultraviolet photodissociation and collision-induced dissociation for qualitative/quantitative analysis of low molecular weight compounds by liquid chromatography-mass spectrometry

“…Untargeted LC–MS screening of organic micro-pollutants ( n = 46) in water samples on a Orbitrap Fusion Lumos equipped with UVPD showed that informative fragments could be generated at 213 nm for compounds that poorly fragment with HCD. Derivatization of a telmisartan, a pharmaceutical compound, with an -idine containing reagent showed at 213-nm rich UVPD spectra compared to HCD which yielded a single fragment [ 15 ]. Comparisons of UVPD and CID spectra on a QqTOF system using a set of aromatic chromophore-containing pharmaceutical compounds (desmethyl bosentan, haloperidol, nelfinavir) showed distinct fragments resulting from photodissociation at 266 or 355 nm [ 16 ].…”

Ultraviolet Photodissociation and Collision Induced Dissociation for Qualitative/Quantitative Analysis of Low Molecular Weight Compounds by Liquid Chromatography-Mass Spectrometry

“…Untargeted LC-MS screening of organic micropollutants (n=46) in water samples on a Orbitrap Fusion Lumos equipped with UVPD showed that informative fragments could be generated at 213 nm for compounds that poorly fragment with HCD. Derivatization of a telmisartan, a pharmaceutical compound, with an -idine containing reagent showed at 213 nm rich UVPD spectra compared to HCD which yielded a single fragment [15]. Comparisons of UVPD and CID spectra on a QqTOF system using a set of aromatic chromophore-containing pharmaceutical compounds (desmethyl bosentan, https://doi.org/10.26434/chemrxiv-2023-t3xpd-v2 ORCID: https://orcid.org/0000-0002-9087-606X Content not peer-reviewed by ChemRxiv.…”