Potential of measured relative shifts in collision cross section values for biotransformation studies
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Author (Corporation)
Publication date
02.12.2023
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01A - Journal article
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Analytical and Bioanalytical Chemistry
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Volume
416
Issue / Number
2
Pages / Duration
559-568
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Springer
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Abstract
Ion mobility spectrometry–mass spectrometry (IMS-MS) separates gas phase ions due to differences in drift time from which reproducible and analyte-specific collision cross section (CCS) values can be derived. Internally conducted in vitro and in vivo metabolism (biotransformation) studies indicated repetitive shifts in measured CCS values (CCSmeas) between parent drugs and their metabolites. Hence, the purpose of the present article was (i) to investigate if such relative shifts in CCSmeas were biotransformation-specific and (ii) to highlight their potential benefits for biotransformation studies. First, mean CCSmeas values of 165 compounds were determined (up to n = 3) using a travelling wave IMS-MS device with nitrogen as drift gas (TWCCSN2, meas). Further comparison with their predicted values (TWCCSN2, pred, Waters CCSonDemand) resulted in a mean absolute error of 5.1%. Second, a reduced data set (n = 139) was utilized to create compound pairs (n = 86) covering eight common types of phase I and II biotransformations. Constant, discriminative, and almost non-overlapping relative shifts in mean TWCCSN2, meas were obtained for demethylation (− 6.5 ± 2.1 Å2), oxygenation (hydroxylation + 3.8 ± 1.4 Å2, N-oxidation + 3.4 ± 3.3 Å2), acetylation (+ 13.5 ± 1.9 Å2), sulfation (+ 17.9 ± 4.4 Å2), glucuronidation (N-linked: + 41.7 ± 7.5 Å2, O-linked: + 38.1 ± 8.9 Å2), and glutathione conjugation (+ 49.2 ± 13.2 Å2). Consequently, we propose to consider such relative shifts in TWCCSN2, meas (rather than absolute values) as well for metabolite assignment/confirmation complementing the conventional approach to associate changes in mass-to-charge (m/z) values between a parent drug and its metabolite(s). Moreover, the comparison of relative shifts in TWCCSN2, meas significantly simplifies the mapping of metabolites into metabolic pathways as demonstrated.
Keywords
Biotransformation assignment, CCSonDemand, Collision cross section, Ion mobility spectrometry mass spectrometry, Metabolite mapping
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ISBN
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1618-2642
1618-2650
1618-2650
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
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Peer review of the complete publication
Open access category
Hybrid
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Citation
Lanshoeft, C., Schütz, R., Lozac’h, F., Schlotterbeck, G., & Walles, M. (2023). Potential of measured relative shifts in collision cross section values for biotransformation studies. Analytical and Bioanalytical Chemistry, 416(2), 559–568. https://doi.org/10.1007/s00216-023-05063-1