Electrochemistry (EC) coupled with liquid chromatography and tandem mass spectrometry (HPLC/ESI-MS/MS) was used to study the oxidation products of cyclosporine A (CYC), everolimus (EWE), mycophenolic acid (MFA), sirolimus (SIR) and… Click to show full abstract
Electrochemistry (EC) coupled with liquid chromatography and tandem mass spectrometry (HPLC/ESI-MS/MS) was used to study the oxidation products of cyclosporine A (CYC), everolimus (EWE), mycophenolic acid (MFA), sirolimus (SIR) and tacrolimus (TAK). Mimicry of the oxidative phase I and II metabolism was achieved in a thin-layer cell equipped with a boron doped diamond (BDD) working electrode. Structures of the electrochemically generated products were elucidated on the basis of MS/MS experiments. Additionally, a sensitive, specific and rapid HPLC-MS/MS method has been developed and validated for the quantification of selected drugs and their metabolites in human serum. Sample preparation was accomplished through microextraction by packed sorbent (MEPS) process. Finally, the identification of electrochemical products was done and results were compared with known metabolites of studied immunosuppressant drugs. Electrochemical conversion of target compounds has appeared as a new pseudo-in vitro instrumental technology for the prediction of potential metabolites, since the oxidation products have also been identified in serum samples.
               
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