HPLC OF BASIC DRUGS AND QUATERNARY AMMONIUM-COMPOUNDS ON MICROPARTICULATE STRONG CATION-EXCHANGE MATERIALS USING METHANOLIC OR AQUEOUS-METHANOL ELUENTS CONTAINING AN IONIC MODIFIER

Sulphopropyl (SCX)-modified silica HPLC columns used with methanolic or aqueous methanol eluents of appropriate pH and ionic strength can give good retention and peak shape for quaternary ammonium compounds and basic drugs. In the system studied, eluent pH influenced retention via protonation of basic analytes, the pKa indicating the pH where retention began to decrease at constant ionic strength. At constant eluent pH retention was inversely proportional to ionic strength for protonated bases and quaternary ammonium compounds. However, this effect was less marked at pH 8.3 as compared to results obtained under acidic conditions. Except for codeine, morphine and lignocaine, the addition of water had no major effects on retention or selectivity at concentrations up to 30% (v/v) at pH 6.7. However, and in contrast to behaviour on unmodified silica, the addition of up to 5% (v/v) water under strongly acidic conditions caused a doubling of retention for most analytes studied. SCX-modified silica columns can be used in the HPLC of a range of basic drugs, including many compounds which are poorly retained on unmodified silica using methanol-rich eluents. The underlying retention mechanism appears to be ion exchange with the SCX moieties, although ionized surface silanols may also contribute to retention at higher eluent pH values. Applications of SCX columns in the HPLC of basic drugs include the analysis of antimalarials such as chloroquine, desethylchloroquine, hydroxychloroquine and quinine, benzodiazepines such as clonazepam, bronchodilators such as salbutamol and terbutaline, cardioactive drugs such as flecainide and lignocaine, and tricyclic antidepressants such as amitriptyline, dothiepin, and imipramine, and their N-demethyl, hydroxyl and sulphoxide metabolites.