Results in Chemistry (Jan 2024)
Comparison of electrochemical and chemical approaches to forced oxidative degradation studies: Abacavir case study
Abstract
This article demonstrates the potential of electrochemical oxidation as an alternative approach to studying the effect of oxidation on active pharmaceutical ingredients. The performance and the outcomes of the electrochemical approach are compared to those of the more common approaches such as peroxide mediated, radical, or metal ion oxidation. The effect of oxidation on abacavir and the effect of the solvent were studied. Electrochemical oxidation was performed using an electrochemical flow cell in static mode, with a glassy carbon electrode (working potential 1.3 V) and a boron-doped diamond electrode (working potential 2.5 V) used as the working electrodes. The glassy carbon electrode was used to monitor the oxidative degradation by electron transfer mechanism and boron-doped diamond electrode was used to monitor the degradation by electron transfer and radical mechanism. The largest amounts of degradation products formed by electrochemical oxidation were observed in a cosolvent consisting of 0.5 M aqueous ammonium acetate pH 7.0 with MeOH (1:9; v/v) in 5 h, 10.6 % and 7.1 % of degradation products were formed on glassy carbon electrode and boron-doped diamond electrode, respectively. Peroxide mediated oxidation in 0.3 % hydrogen peroxide for 72 h at ambient temperature yielded the most degradation products, i.e., 8.7 %, in cosolvent consisting of 0.5 M ammonium acetate, pH 7.0, with MeOH (1:1; v/v). The third approach was radical oxidation using AIBN as a radical initiator at a concentration of 20 mol % at 50 °C for 7 days. The most degradation products, i.e., 34.2 %, formed by radical oxidation were observed in pure MeOH. The last approach tested was oxidation using metal ions. A 1.0 mmol/l FeCl3 solution was used and the oxidation took place for 7 days at 50 °C. During the metal ion oxidation, the most degradation products, i.e., 25.7 % were formed in pure MeOH.
