Unusual (+/–)‐electrospray ionization induced fragmentation: Structural elucidation of an in‐process synthetic intermediate of doravirine (MK‐1439) using liquid chromatography/high‐resolution tandem mass spectrometry and two‐dimensional nuclear magnetic resonance

Sheng, Huaming; Lexa, Katrina W.; Zhang, Li‐Kang; Yang, Rong-Sheng; Wright, Timothy J.; Sherry, Benjamin D.; Helmy, Roy; Martin, Gary E.

doi:10.1002/rcm.7833

Cited by 1 publication

(1 citation statement)

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“…However, in some cases, ESI can unusually lead to non‐reported adducts or fragments 7, 8 . This becomes detrimental to annotation because these are not included in automated pipelines for compound identification.…”

Section: Introductionmentioning

confidence: 99%

Detection of ergosterol using liquid chromatography/electrospray ionization mass spectrometry: Investigation of unusual in‐source reactions

Ory

Gentil

Kumla

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale:In the field of natural products, de-replication of complex mixtures has become a usual practice to annotate known compounds and avoid their re-isolation.For this purpose, many groups rely on liquid chromatography coupled to highresolution mass spectrometry (HPLC/MS) to deduce molecular formulae of compounds allowing comparison with public or in-house databases. Electrospray ionization (ESI) is usually considered as the method of choice for investigating a large panel of compounds but, in some cases, it may lead to unusual results as described in this article for ergosterol. Methods: Ergosterol and other fungal sterols in methanolic solution were analysed using various chromatographic gradients with HPLC/MS using both ion trap time-offlight MS and Orbitrap MS instruments fitted with an ESI source. Further flow injection analyses were performed to investigate the influence of the solvent composition. MS/MS fragmentation data were acquired to annotate the various ions observed.Results: Contrary to other fungal sterols, ergosterol was found to be highly sensitive to oxidation during ESI. Putative structures were proposed based on MS/MS studies and known oxidation mechanisms of ergosterol by reactive oxygen species that could be formed in the ESI process. The proportion of acetonitrile in the eluent was found to influence this in-source oxidation, with an increased proportion of oxidized sodium adducts with higher proportions of acetonitrile. Conclusions:While ergosterol is a major sterol found in fungi, this study investigates its ionization by electrospray for the first time. The results reported here will help further detection and annotation of this compound in fungal extracts after HPLC/ESI-MS analyses.

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Section: Introductionmentioning

confidence: 99%