Separation of selected basic pharmaceuticals by reversed-phase and ion-exchange chromatography using thermally tuned tandem columns

The separation of basic pharmaceuticals is usually performed on C8 or C18 b onded silica supports. Silanolphilic interactions between basic analytes an d surface silanol groups often lead to tailed peaks, poor efficiency, and i rreproducible retention times. To solve these problems, many new types of s ilica-, zirconia-, and polymer-based columns, which provide unique selectiv ities, improved stability at high pH, or both, have been developed for the analysis of basic compounds. The essence of method development for the chro matographic analysis of basic compounds is to choose a system in which the band spacing can be varied dramatically, quickly, and conveniently while mi nimizing the tailing due to silanolphilic interactions. The thermally tuned tandem column ((TC)-C-3) approach has been shown to provide an effective w ay to adjust stationary-phase selectivity for nonionic compounds. In this s tudy, a tandem combination of an octadecylsilane (ODS) and a polybutadiene- coated zirconia (PBD-ZrO2) phase was used to separate nine antihistamines. Selectivity is tuned by independently adjusting the isothermal temperatures of the two columns. We found dramatic differences in the retention factors , elution sequences, and band spacing for the above set of basic drugs on t he two types of columns. The (TC)-C-3 model has been used successfully to l ocate the optimal temperatures based on only four exploratory runs. The nin e antihistamines were baseline separated on the tandem column combination e ven though they could not be separated on the individual phases. The effect of the buffer concentration on retention of the basic antihistamines was a lso studied. We conclude that cation-exchange interactions predominate on t he PBD-ZrO2 phase, while reversed phase interactions are more important on the ODS phase. Interestingly, an increase in column temperature causes a si gnificant increase in the retention on the ODS column and a decrease of ret ention on the PBD-ZrO2 column. This can be explained by the change in the a nalyte's degree of ionization with temperature. The (TC)-C-3 combination of silica- and zirconia-based RPLC columns is demonstrated to be a powerful a pproach for the separation of this mixture of basic analytes.