The electrochemical behaviour of desloratadine (DLOR) and its derivative 3-hydroxydesloratadine (3OH-DLOR) was investigated by direct current (DCP) polarography, cyclic (CV), differential pulse (DPV) and square-wave (SWV) voltammetry in Britton-Robinson (BR) buffer solutions (pH 4-11). Both compounds are reduced at mercury electrode in irreversible two electron reduction of the C=N bond of the pyridine ring in their molecules. The difference in their electrochemical behaviour was investigated, and the most pronounced distinction is observed at pH > 9, as a consequence of the deprotonation of the phenolic moiety in 3OH-DLOR molecule, yielding significant change in their reduction potentials (Ep DLOR = -1.48 V, and Ep 3OH-DLOR = -1.6 V). The observed results correlate with calculated LUMO energy levels and Hammet substituent constants (σ). Based on the difference in the reduction potential for DLOR and 3OH-DLOR, conditions for simultaneous determination these two molecules in alkaline medium were established. The best selectivity was achieved using SWV method at pH 10. The linearity of the calibration graphs were achieved in the concentration range from 1.5 × 10-6 M - 1 × 10-5 M for DLOR and 7.5 × 10-6 M - 5 × 10-5 M for 3OH-DLOR with detection limits of 2.29 × 10-7 M and 2.08 × 10-6 M, and determination limits of 7.64 × 10-7 M and 6.94 × 10-6 M, for DLOR and 3OH-DLOR, respectively. The method was checked in human plasma sample. Good response was obtained with LOD and LOQ values of 4.63 × 10-7 M and 1.54 × 10-6 M, for DLOR and 2.39 × 10-6 M and 7.97 × 10-6 M, 3OH-DLOR, respectively.