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 o r aqueous methanol eluents of appropriate pH and ionic strength can gi ve good retention and peak shape for quaternary ammonium compounds and basic drugs. In the system studied, eluent pH influenced retention vi a protonation of basic analytes, the pKa indicating the pH where reten tion began to decrease at constant ionic strength. At constant eluent pH retention was inversely proportional to ionic strength for protonat ed bases and quaternary ammonium compounds. However, this effect was l ess marked at pH 8.3 as compared to results obtained under acidic cond itions. Except for codeine, morphine and lignocaine, the addition of w ater had no major effects on retention or selectivity at concentration s 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 st udied. 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 retentio n mechanism appears to be ion exchange with the SCX moieties, although ionized surface silanols may also contribute to retention at higher e luent pH values. Applications of SCX columns in the HPLC of basic drug s include the analysis of antimalarials such as chloroquine, desethylc hloroquine, hydroxychloroquine and quinine, benzodiazepines such as cl onazepam, bronchodilators such as salbutamol and terbutaline, cardioac tive drugs such as flecainide and lignocaine, and tricyclic antidepres sants such as amitriptyline, dothiepin, and imipramine, and their N-de methyl, hydroxyl and sulphoxide metabolites.