In this study electrochemistry (EC) coupled with electrospray ionization mass spectrometry (ESI-MS) was used to study the metabolic fate of three novel cardiovascular drugs: rivaroxaban (RIV), aliskiren (ALS), and prasugrel (PRS). Mimicry of the oxidative phase I metabolism was achieved in a simple amperometric thin-layer cell equipped with a boron-doped diamond (MD) working electrode. Structures of the electrochemically-generated metabolites were elucidated from MS/MS experiments. Additionally, a sensitive, specific, and rapid ultra-high performance liquid chromatography–tandem mass spectrometer (UHPLC–MS/MS) method has been developed and validated for the selected drugs in human urine samples. Three different sample preparation methods were compared and finally, sample preparation was accomplished through an ultrasound-assisted emulsification microextraction process (USAEME). The drugs were detected using a triple quadrupole tandem mass spectrometer by multiple reaction monitoring via an electrospray ionization source with positive ionization mode (ESI(+)). The results obtained by EC–MS were compared with conventional in vivo studies by analyzing urine samples from patients. Data from in vivo experiments showed good agreement with the data from electrochemical oxidation. Thus, EC–MS is very well-suited for the simulation of the oxidative metabolism of rivaroxaban, aliskiren, and prasugrel as well. Moreover, electrochemical conversion of target compounds appears to be a new in vitro technology for the prediction of potential metabolites.

在这项研究中，电化学（EC）结合电喷雾电离质谱（ESI-MS）用于研究三种新型心血管药物的代谢命运：利伐沙班（RIV），阿利吉仑（ALS）和普拉格雷（PRS）。在配备有掺硼金刚石（MD）工作电极的简单安培薄层电池中实现了I相氧化代谢的模仿。从MS / MS实验中阐明了电化学生成的代谢物的结构。此外，已经开发了灵敏，特异且快速的超高效液相色谱-串联质谱仪（UHPLC-MS / MS）方法，并已针对人尿液样品中的选定药物进行了验证。比较了三种不同的样品制备方法，最后，样品制备是通过超声辅助乳化微萃取工艺（USAEME）完成的。使用三重四极杆串联质谱仪通过多反应监测来检测药物通过具有正电离模式（ESI（+））的电喷雾电离源。通过分析患者尿液样本，将EC-MS获得的结果与传统的体内研究进行了比较。体内实验数据显示与电化学氧化数据吻合良好。因此，EC-MS非常适合模拟利伐沙班，阿利吉仑和普拉格雷的氧化代谢。此外，目标化合物的电化学转化似乎是预测潜在代谢产物的一项新的体外技术。