Differentiating Isomeric Deprotonated Glucuronide Drug Metabolites via Ion/Molecule Reactions in Tandem Mass Spectrometry,Analytical Chemistry

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Differentiating Isomeric Deprotonated Glucuronide Drug Metabolites via Ion/Molecule Reactions in Tandem Mass Spectrometry
Analytical Chemistry ( IF 6.7 ) Pub Date : 2018-07-09 00:00:00 , DOI: 10.1021/acs.analchem.8b02083
John Y. Kong ₁ , Zaikuan Yu ₁ , Mckay W. Easton ₁ , Edouard Niyonsaba ₁ , Xin Ma ₁ , Ravikiran Yerabolu ₁ , Huaming Sheng ₂ , Tiffany M. Jarrell ₃ , Zhoupeng Zhang ₄ , Arun K. Ghosh ₁ , Hilkka I. Kenttämaa ₁

Affiliation

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.

中文翻译：

通过串联质谱中的离子/分子反应区分异构的去质子化的葡萄糖醛酸苷药物代谢物

异构O-和N-葡萄糖醛酸苷是药物代谢II期产生的常见药物代谢产物。通过使用常规分析技术区分这些异构体已证明具有挑战性。据报道，在线性四极杆离子阱质谱仪中，基于去质子化的葡萄糖醛酸苷药物代谢物与三氯硅烷（HSiCl ₃）的气相离子/分子反应的串联质谱法可轻松区分O和N异构体。HSiCl ₃与去质子化的N-葡萄糖醛酸化物反应时观察到的主要产物离子是诊断性的HSiCl ₃加合物，失去了两个HCl分子（[M – H + HSiCl₃ – 2HCl]-）。对于去质子化的O-葡萄糖醛酸苷，未观察到该产物离子。在M06-2X / 6-311 ++ G（d，p）的理论水平上通过量子化学计算探索了反应机理。

更新日期：2018-07-09

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