Department of Chemistry and Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Rondebosch, 7701, South Africa.
Rapid Commun Mass Spectrom. 2012 Oct 30;26(20):2431-42. doi: 10.1002/rcm.6359.
Artemisinin-based drugs and their metabolites are prone to in-source fragmentation under atmospheric pressure ionisation mass spectrometry (API-MS) conditions. To facilitate correct and efficient identification of all possible drug metabolites using full scan MS analyzer methods, stable M + NH(4) ions should be produced in the MS source.
Using a high-performance liquid chromatography (HPLC) hybrid triple quadrupole linear ion trap MS system, electrospray ionisation (ESI), atmospheric pressure chemical ionisation (APCI) and atmospheric pressure photoionisation (APPI) methods were developed for the detection of M + NH(4) ions of the test compounds dihydroartemisinin, artemisinin, artemether and artesunic acid. The optimised methods employed ammonium formate buffered HPLC mobile phase in combination with moderate source temperatures (100-200 °C) and showed satisfactorily reduced in-source fragmentation.
With a full scan MS analyser method for the detection of the in vitro metabolites of the test compounds, the respective performance of the ESI and APCI methods was found to be comparable. ESI generally resulted in less in-source fragmentation. Incorrect assignment of metabolites resulted from strong in-source fragmentation of artemether using the APPI method. The most number of metabolites could be detected using ESI in combination with a selective MS analyser method.
ESI and APCI full scan methods proved to be capable of detecting any drug metabolites present in reasonable concentrations, and are useful when employed in addition to selective scan methods that target low level expected metabolites. APPI can be a valuable alternative for detecting expected metabolites due to good signal-to-noise (S/N) ratio.
在大气压电离质谱（API-MS）条件下，青蒿素类药物及其代谢物容易在源内发生碎裂。为了使用全扫描 MS 分析器方法方便、正确、有效地鉴定所有可能的药物代谢物，MS 源中应产生稳定的[M+NH4+]离子。
使用高效液相色谱（HPLC）混合三重四极杆线性离子阱 MS 系统，开发了电喷雾电离（ESI）、大气压化学电离（APCI）和大气压光离子化（APPI）方法，用于检测二氢青蒿素、青蒿素、青蒿琥酯和青蒿酸测试化合物的[M+NH4+]离子。优化后的方法采用甲酸铵缓冲 HPLC 流动相，结合中等的源温度（100-200°C），显示出令人满意的减少源内碎裂。
使用全扫描 MS 分析器方法检测测试化合物的体外代谢物，发现 ESI 和 APCI 方法的各自性能相当。ESI 通常导致较少的源内碎裂。APPI 方法由于青蒿琥酯的强烈源内碎裂，导致代谢物的错误分配。使用 ESI 结合选择性 MS 分析器方法，可以检测到最多数量的代谢物。
ESI 和 APCI 全扫描方法被证明能够检测到合理浓度下存在的任何药物代谢物，并且在与靶向低水平预期代谢物的选择性扫描方法一起使用时非常有用。APPI 可以是一种有价值的替代方法，因为它具有良好的信噪比（S/N）。
