Dual CD system-modified MEEKC method for the determination of clemastine and its impurities.

A dual system of CDs was used for the first time in MEEKC with the aim of determining clemastine and its three main related impurities in both drug substances and tablets. The addition of methyl-β-cyclodextrin and heptakis(2,6-di-O-methyl)-β-cyclodextrin to the microemulsion pseudo-stationary phase was essential to increase the resolving power of the system to obtain a baseline separation among the compounds. The best microemulsion composition was identified by mixture design and the effects of the factors concentrations of CDs and voltage were investigated by a response surface study applying a Central Composite Design. In both cases, Derringer's desirability function made it possible to find the global optimum, which corresponded to the following combination: microemulsion, 89.8% 10 mM borate buffer pH 9.2, 1.5% n-heptane and 8.7% of SDS/n-butanol in 1:2 ratio; 18 mM methyl-β-cyclodextrin, 38 mM heptakis(2,6-di-O-methyl)-β-cyclodextrin, 17 kV. By applying these conditions, the separation was completed in about 5.5 min. The method was validated following International Conference on Harmonisation guidelines and was applied to a real sample of clemastine tablets.