Electrochemical simulation of three novel cardiovascular drugs phase I metabolism and development of a new method for determination of them by liquid chromatography coupled with tandem mass spectrometry

Abstract

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.