Ma Shuguang, Chowdhury Swapan K, Alton Kevin B
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA.
Anal Chem. 2005 Jun 1;77(11):3676-82. doi: 10.1021/ac048203j.
N-Oxides are known to undergo deoxygenation during atmospheric pressure chemical ionization (Ramanathan, R.; Su, A.-D.; Alvarez, N.; Blumenkrantz, N.; Chowdhury, S. K.; Alton, K.; Patrick, J. Anal. Chem. 2000, 72, 1352-1359) resulting from thermal energy activation at the vaporizer of the APCI source. In addition to deoxygenation, tert-N-oxides containing an alkyl or benzyl group on the N-oxide nitrogen also undergo an N-R to O-R rearrangement (Meisenheimer arrangement, where R = alkyl or benzyl), followed by elimination of an aldehyde (or a ketone) through an internal hydrogen transfer. This has been observed under both atmospheric pressure chemical ionization and atmospheric pressure photoionization conditions. These fragment ions were not observed in the product ion spectra from the protonated molecules of the corresponding N-oxides. The elimination of an aldehyde or a ketone, thus, results from thermal energy activation at the vaporizer and is not induced by collisional activation. These fragmentations not only distinguish N-oxides from isomeric hydroxylated metabolites but also provide a potential way to determine the position of N-oxidation when a metabolite (or molecule) contains multiple N-oxidation sites that are in different chemical environments.
已知在大气压化学电离过程中，N-氧化物会发生脱氧反应（拉马纳坦，R.；苏，A.-D.；阿尔瓦雷斯，N.；布卢门克兰茨，N.；乔杜里，S. K.；奥尔顿，K.；帕特里克，J.《分析化学》2000年，72卷，1352 - 1359页），这是由于大气压化学电离源蒸发器处的热能激活所致。除了脱氧反应外，在N-氧化物氮原子上含有烷基或苄基的叔N-氧化物还会发生N-R到O-R的重排（迈森海默重排，其中R =烷基或苄基），随后通过分子内氢转移消除醛（或酮）。在大气压化学电离和大气压光电离条件下均观察到了这种情况。在相应N-氧化物质子化分子的产物离子谱中未观察到这些碎片离子。因此，醛或酮的消除是由蒸发器处的热能激活引起的，而非碰撞激活诱导的。这些碎片化不仅能将N-氧化物与异构羟基化代谢物区分开来，而且当代谢物（或分子）含有处于不同化学环境的多个N-氧化位点时，还提供了一种确定N-氧化位置的潜在方法。
