Differentiating Isomeric Deprotonated Glucuronide Drug Metabolites via Ion/Molecule Reactions in Tandem Mass Spectrometry
| Autor: | Mckay W Easton, Hilkka I. Kenttämaa, John Kong, Edouard Niyonsaba, Zhoupeng Zhang, Arun K. Ghosh, Zaikuan Yu, Tiffany M. Jarrell, Huaming Sheng, Xin Ma, Ravikiran Yerabolu |
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| Rok vydání: | 2018 |
| Předmět: |
Reaction mechanism
010405 organic chemistry Chemistry Silanes 010402 general chemistry Mass spectrometry Tandem mass spectrometry 01 natural sciences Medicinal chemistry Article 0104 chemical sciences Analytical Chemistry Ion Adduct Glucuronides Isomerism Pharmaceutical Preparations Tandem Mass Spectrometry Molecule Quadrupole ion trap Protons Glucuronide Chromatography High Pressure Liquid |
| Zdroj: | Analytical chemistry. 90(15) |
| ISSN: | 1520-6882 |
| Popis: | Isomeric O- and N-glucuronides are common drug metabolites produced in phase II of drug metabolism. Distinguishing these isomers by using common analytical techniques has proven challenging. A tandem mass spectrometric method based on gas-phase ion/molecule reactions of deprotonated glucuronide drug metabolites with trichlorosilane (HSiCl3) in a linear quadrupole ion trap mass spectrometer is reported here to readily enable differentiation of the O- and N-isomers. The major product ion observed upon reactions of HSiCl3 with deprotonated N-glucuronides is a diagnostic HSiCl(3) adduct that has lost two HCl molecules ([M − H + HSiCl3 − 2HCl]-). This product ion was not observed for deprotonated O-glucuronides. Reaction mechanisms were explored with quantum chemical calculations at the M06-2X/6-311++G(d,p) level of theory. |
| Databáze: | OpenAIRE |
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