Lohmann Wiebke, Meermann Björn, Möller Ines, Scheffer Andy, Karst Uwe
Institut für Anorganische and Analytische Chemie, Westfälische Wilhelms-Universität Munster, Corrensstrasse 30, 48149 Münster, Germany.
Anal Chem. 2008 Dec 15;80(24):9769-75. doi: 10.1021/ac801878k.
For the risk assessment of drug candidates, the identification and quantification of their metabolites is required. The majority of analytical techniques is based on calibration standards for quantification of the metabolites. As these often are not readily available, the use of inductively coupled plasma mass spectrometry (ICPMS) is an attractive alternative for drugs containing heteroatoms. In this work, the online coupling of electrochemistry (EC), liquid chromatography (LC), and ICPMS is presented. The antiarrhythmic agent amiodarone, which contains two iodine atoms, is oxidized in an electrochemical flow-through cell under N-dealkylation and deiodination. The metabolites that are generated at different EC potentials are identified by electrospray ionization (ESI) mass spectrometry, compared to those from rat liver microsomal incubations and quantified by ICPMS. Phase-optimized LC, a recent approach for high-performance isocratic separations, is used to avoid the ICPMS calibration problems known to occur with gradient separations. The potential of the complementary use of ESI-MS and ICPMS for the qualitative and quantitative analysis of drug metabolites becomes apparent in this work.
对于候选药物的风险评估，需要鉴定和定量其代谢物。大多数分析技术基于代谢物定量的校准标准品。由于这些标准品往往不易获得，对于含杂原子的药物，电感耦合等离子体质谱法（ICPMS）是一种有吸引力的替代方法。在这项工作中，介绍了电化学（EC）、液相色谱（LC）和ICPMS的在线联用。抗心律失常药物胺碘酮含有两个碘原子，在电化学流通池中在N-脱烷基化和脱碘作用下被氧化。通过电喷雾电离（ESI）质谱法鉴定在不同EC电位下产生的代谢物，并与大鼠肝微粒体孵育产生的代谢物进行比较，然后通过ICPMS进行定量。相优化液相色谱是一种用于高效等度分离的最新方法，用于避免梯度分离中已知的ICPMS校准问题。在这项工作中，ESI-MS和ICPMS互补用于药物代谢物定性和定量分析的潜力显而易见。
