Utility of Screen Printed Electrodes for in Vitro Metabolic Stability Assays: Application to Acetaminophen and its Thioconjugates

Abstract

Screen printed electrodes (SPEs), in addition to their utility in the electrochemical quantification of compounds of pharmacological interest may be used (i) for studying the redox pattern of drug candidates by cyclic voltammetry, (ii) for electrochemical synthesis in microvolumes (microelectrosynthesis) at a selected applied potential with subsequent off-line LC-MS identification of the generated products, and (iii) for monitoring enzymatic reactions in microvolumes of samples. The resulting data are of valuable predictive value for in vitro metabolic stability assays. Acetaminophen (APAP) was used as relevant model drug compound to illustrate potential applications of SPEs in pharmaceutical research. The electrooxidation of APAP was studied, in the absence and presence of endogenous thiols, in microvolume sample by cyclic voltammetry and by microelectrolysis at a carbon based SPE (CSPE) and the generated products were identified off-line by liquid chromatography coupled to mass spectrometry (LC-MS).

Electrochemical and Hyphenated Electrochemical Detectors in Liquid Chromatography and Flow Injection Systems for Drug Compound Analysis

“…Instead of online flow system, an off-line EC-MS application can also be performed as illustrated by the voltammetric investigation of paracetamol at a carbon-based screen-printed electrode. The electrolysis of paracetamol in the absence or presence of glutathione in a few microliters of sample (50 μL) deposited on the SPE with subsequent injection into the LC-MS setup permitted to identify paracetamol phase I and phase II metabolites [61].…”

Electrochemistry of Eugenol and its Metabolism on a Bare Screen-Printed Electrode

“…Screen-printed electrodes (SPEs), are low cost disposable sensors with a three-electrode configuration (Working, Reference and Counter electrodes), providing in this way a miniaturized electrochemical cell. In literature, their capability on investigating drug formulations with their corresponding metabolites is limited (Radi et al, 2013;Kauffmann et al, 2011). Thus, further studies with different types of phase I reactions and multiple pathways are required to prove the efficient use of SPE in metabolism.…”

Simulating the phase II metabolism of raloxifene on a screen-printed electrode

“…Screen-printed electrodes (SPEs) are inexpensive sensors widely used in electroanalytical chemistry. Major applications include forensics [13] , drug formulations [14] , metabolism [15] and microbiology [16] . Ideal for research and routine analysis offering disposability, portability, low cost and low volume of reagent [14,15] .…”

“…Major applications include forensics [13] , drug formulations [14] , metabolism [15] and microbiology [16] . Ideal for research and routine analysis offering disposability, portability, low cost and low volume of reagent [14,15] . SPEs are fabricated from inks printed into ceramic or plastic substrates [17,18,19] .…”

“…However, the exact ink formulation in commercially available sensors is unknown to the users. The three-electrode configuration provides a fully functional cell in a miniaturized format for both detection and synthesis [15,19,20] . In the present study, we describe the mimicry of RLX metabolism on a bare 4 SPE.…”