Identification of N-Oxide and Sulfoxide Functionalities in Protonated Drug Metabolites by Using Ion-Molecule Reactions Followed by Collisionally Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer.
Identification of N-Oxide and Sulfoxide Functionalities in Protonated Drug Metabolites by Using Ion-Molecule Reactions Followed by Collisionally Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer.
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通过在线性四极离子阱质谱仪中使用离子分子反应和碰撞激活解离来鉴定质子化药物代谢物中的氮氧化物和亚砜功能。
DOI：
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发表时间：
2016
影响因子：
3.6
通讯作者：
H. Kenttämaa
中科院分区：
文献类型：
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作者：
Huaming Sheng;Weijuan Tang;Ravikiran Yerabolu;J. Max;Raghavendhar R. Kotha;James S. Riedeman;John J Nash;Minli Zhang;H. Kenttämaa
许多药物中的硫和氮原子在体内氧化成亚砜和N-氧化物官能团是常见的生物转化过程。不幸的是，这些代谢物的明确鉴定可能具有挑战性。在本研究中，三（二甲氨基）硼烷的离子-分子反应，然后在离子阱质谱仪中的碰撞活化解离（CAD）被证明可以识别质子化的多功能药物代谢产物中的N-氧化物和亚砜官能团。只有离子与N-氧化物或亚砜功能形成诊断加合物，失去了二甲胺（DMA）。即使对于含有比感兴趣的官能团基本上更碱性的官能团的分析物也证明了这一点。诊断产物离子（M）的CAD主要导致N-氧化物的A型（M-DMA）和B碎片离子（M-HO-B（N（CH 3）2）2），但亚砜也形成诊断C离子（M-O-BN（CH 3）2），从而允许区分官能度。一些质子化的分析物产生了丰富的TDMAB加合物，失去了两个DMA分子，而不仅仅是一个。这提供了关于N-氧化物和亚砜官能团的环境的信息。通过量子化学计算探讨了上述反应的机理。该方法可用于真实的药物分析。
The in vivo oxidation of sulfur and nitrogen atoms in many drugs into sulfoxide and N-oxide functionalities is a common biotransformation process. Unfortunately, the unambiguous identification of these metabolites can be challenging. In the present study, ion-molecule reactions of tris(dimethylamino)borane followed by collisionally activated dissociation (CAD) in an ion trap mass spectrometer are demonstrated to allow the identification of N-oxide and sulfoxide functionalities in protonated polyfunctional drug metabolites. Only ions with N-oxide or sulfoxide functionality formed diagnostic adducts that had lost dimethyl amine (DMA). This was demonstrated even for an analyte that contains a substantially more basic functionality than the functional group of interest. CAD of the diagnostic product ions (M) resulted mainly in type A (M - DMA) and B fragment ions (M - HO-B(N(CH3)2)2) for N-oxides, but sulfoxides also formed diagnostic C ions (M - O═BN(CH3)2), thus allowing differentiation of the functionalities. Some protonated analytes yielded abundant TDMAB adducts that had lost two DMA molecules instead of just one. This provides information on the environment of the N-oxide and sulfoxide functionalities. Quantum chemical calculations were performed to explore the mechanisms of the above-mentioned reactions. The method can be implemented on HPLC for real drug analysis.
DOI：
10.2174/187152607781001772
发表时间：
2007-05
期刊：
Infectious disorders drug targets
影响因子：
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作者：
Devayani P. Bhave;W. Muse;Kate S. Carroll
通讯作者：
Devayani P. Bhave;W. Muse;Kate S. Carroll