Identification of Protonated Primary Carbamates by Using Gas-Phase Ion–Molecule Reactions Followed by Collision-Activated Dissociation in Tandem Mass Spectrometry Experiments
| Autor: | Leah F. Easterling, Mckay W Easton, Hilkka I. Kenttämaa, Zhoupeng Zhang, John Kong, Judy Liu, Zaikuan Yu, Jacob Milton, Huaming Sheng, Edouard Niyonsaba |
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| Rok vydání: | 2019 |
| Předmět: |
010405 organic chemistry
Chemistry Organic Chemistry Protonation Atmospheric-pressure chemical ionization 010402 general chemistry Tandem mass spectrometry Mass spectrometry 01 natural sciences Dissociation (chemistry) 0104 chemical sciences Adduct Computational chemistry Ion trap Physical and Theoretical Chemistry Quadrupole ion trap |
| Zdroj: | Organic Process Research & Development. 23:1159-1166 |
| ISSN: | 1520-586X 1083-6160 |
| DOI: | 10.1021/acs.oprd.9b00080 |
| Popis: | The levels of potentially mutagenic impurities (PMIs) in active pharmaceutical ingredients are highly regulated and must be below a critical safety threshold. One class of PMIs is primary carbamates, which are formed during drug manufacturing and formulation. To comply with safety regulations, it is critically important to develop analytical techniques that enable the identification of primary carbamates during the drug development process. In this study, tandem mass spectrometry combined with gas-phase ion–molecule reactions as well as collision-activated dissociation (CAD) is demonstrated to enable the identification of protonated primary carbamates. Primary carbamates were protonated via atmospheric pressure chemical ionization (APCI) in a linear quadrupole ion trap mass spectrometer, isolated, and allowed to react with trimethoxymethylsilane (TMMS) introduced into the ion trap via an external reagent mixing manifold. Protonated primary carbamates reacted with TMMS to form an adduct ion, [M + H + TMMS]... |
| Databáze: | OpenAIRE |
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