Differentiating Isomeric Deprotonated Glucuronide Drug Metabolites via Ion/Molecule Reactions in Tandem Mass Spectrometry.
John Y KongZaikuan YuMckay W EastonEdouard NiyonsabaXin MaRavikiran YeraboluHuaming ShengTiffany M JarrellZhoupeng ZhangArun K GhoshHilkka I KenttämaaPublished in: Analytical chemistry (2018)
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 HSiCl3 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.
Keyphrases
- tandem mass spectrometry
- liquid chromatography
- phase ii
- ms ms
- ultra high performance liquid chromatography
- high performance liquid chromatography
- clinical trial
- mass spectrometry
- gas chromatography
- simultaneous determination
- high resolution
- molecular dynamics
- adverse drug
- drug induced
- magnetic resonance imaging
- emergency department
- magnetic resonance
- computed tomography
- solid phase extraction
- density functional theory
- randomized controlled trial
- electronic health record
- monte carlo