Voltammetric behaviour of bromhexine and its determination in pharmaceuticals

Abstract

A complete electrochemical study and a novel electroanalytical procedure for brombexine quantitation are described. Bromhexine in methanol/0.1 mol L-1 Britton-Robinson buffer solution (2.5/97.5) shows an anodic response on glassy carbon electrode between pH 2 and 7.5. By DPV and CV, both peak potential and current peak values were pH-dependent in all the pH range studied. A break at pH 5.5 in Ep versus pH plot revealing a protonation-deprotonation (pK(a)) equilibrium of brombexine was observed. Spectrophotometrically, an apparent pK, value of 4.3 was also determined. An electrodic mechanism involving the oxidation of bromhexine via two-electrons and two-protons was proposed. Controlled potential electrolysis followed by HPLC-UV and GC-MS permitted the identification of three oxidation products: N-methylcyclohexanamine, 2-amino-3,5-dibromobenzaldehyde and 2,4,8,10-tetrabromo dibenzo[b,f][1,5] diazocine.

DPV at pH 2 was selected as optimal pH for analytical purposes. Repeatability, reproducibility and selectivity parameters were adequate to quantify bromhexine in pharmaceutical forms. The recovery was 94.50 +/- 2.03% and the detection and quantitation limits were 1.4 x 10(-5) and 1.6 x 10(-5) mol L-1, respectively. Furthermore, the DPV method was applied successfully to individual tablet assay in order to verify the uniformity content of bromhexine. No special treatment of sample were required due to excipients do not interfered with the analytical signal. Finally the method was not time-consuming and less expensive than the HPLC one.