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A three-leveled Plackett-Burman experimental design was used for the optimization of enantiomeric separation of chlorpheniramine by capillary zone electrophoresis using hydroxypropyl-β-cyclodextrin as chiral recognition agent. In this study, the effects of five important factors, namely, pH of the buffer, concentration of chiral selector, organic cations composing the background electrolyte, organic solvent and applied voltage upon resolution, migration time, and peak efficiency were investigated. The optimum separation conditions deduced from the effects were used to determine the amount of the (−)-isomer as impurity in a (+)-chlorpheniramine raw substance and two dexchlorpheniramine commercial tablets. It was found that the impurity levels were between 1 and 2%.

Based on previous work using the uni-variate approach to optimize the separation of nine Lauraceous aporphine alkaloids, lindcarpine, laurolitsine, N-methyllindcarpine, boldine, norpredicentrine, isocorydine, laurotetanine, N-methyl-laurotetanine, and isoboldine, by micellar electrokinetic chromatography, a three-parameter overlapping resolution mapping (ORM) scheme was employed to optimize the separation of these compounds. With the other conditions preoptimized, three buffer parameters, i.e., the concentrations of sodium borate, sodium dodecylsulfate, and sodium heptanesulfonate were chosen to carry out the optimization process. Conditions were identified that allowed base-line separation of the nine aporphines and the internal standard within eight minutes. These results show that ORM is an efficient optimization procedure, although some primary separation data is first required.