Electrochemical oxidation mechanism of ambroxol and its voltammetric determination in the presence of dodecyl sulfate

Graphical abstract: The possible oxidation mechanism of ambroxol involves that amino group is irreversibly oxidized to produce an active anilino-radical at a higher potential. Then the free radicals dimerize via 'head-to-tail' coupling to yield a dimer 4-amino-diphenylamine derivative. This dimer is reduced and oxidized quasi-reversibly at a lower potential. -- Highlights: •The voltammetric behavior of ambroxol was studied in detail for the first time. •The possible oxidation mechanism of ambroxol was clearly demonstrated. •The mechanism explained the different scavenging effect of ambroxol on reactive oxygen species reasonably. •SDS played two roles in changing interface properties and stabilizing the free radical of ambroxol. •A more sensitive method was proposed for the voltammetric determination of ambroxol. -- Abstract: The voltammetric behavior of ambroxol (AMB) at carbon paste electrode (CPE) in acidic aqueous solution was studied in this work. The possible oxidation mechanism was suggested that amine group of AMB underwent a two-electron and two-proton oxidation to produce an anilino-radical at the higher potential around 1 V (vs. SCE), showing an irreversible oxidation peak. Subsequently, the anilino-radicals dimerized via 'head-to-tail' coupling to yield a corresponding 4-amino-diphenylamine derivative in its oxidized form. This generated dimer was reduced and oxidized in the lower potential range of 0.1–0.39 V (vs. SCE), showing a pair of quasi-reversible redox peak. With the mechanism, the different scavenging effect of AMB on reactive oxygen species (ROS) was attributed to that different species of AMB take part in the reaction with ROS. In the case of electrochemical oxidation of AMB, anionic surfactant sodium dodecyl sulfate (SDS) was found to play a dual function in eliminating the electrostatic repulsion between the protonated AMB and the CPE with high positive potential and prolonging the lifetime of the anilino-radical of AMB oxidation. In 0.1 M HAc-NaAc buffer (pH 5.0) solution containing 3.0 × 10−4 M SDS, the oxidation peak of amine group of AMB appeared at 0.93 V (vs. SCE) and the peak current enhanced by 4.5 times in comparison to that in the absence of SDS. Based on this, a single-sweep voltammetric method was proposed for the determination of AMB. The second-order derivative peak current of AMB was rectilinear with its concentration in the range of 3.0 × 10−8–4.0 × 10−7 M. The limit of detection was 5.4 × 10−9 M. The sensitivity of the determination of AMB was improved, the oxidation potential of AMB was reduced and the experimental condition was moderated