HPLC of basic drugs on microparticulate strong cation-exchange materials — a review

Abstract

Propylsulphonic acid (SCX)-modified silica HPLC columns used with methanol or aqueous methanol eluents of appropriate pH and ionic strength can give good retention and peak shape for basic drugs. In the system studied, eluent pH influenced retention via protonation of basic analytes, the p K a of the analyte indicating the pH where retention begins to decrease at constant ionic strength. At constant pH, retention is inversely proportional to ionic strength for protonated bases and quaternary ammonium compounds. 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. In capillary electrochromatography (CEC) unprecedented efficiencies, but similar selectivity, to that observed in conventional HPLC have been obtained for a standard range of basic drugs using Waters Spherisorb S3SCX. SCX-modified silica columns can be used in the HPLC of many basic drugs, including some compounds that are poorly retained on unmodified silica using methanol-rich eluents. N-Desalkyl and sulphoxide metabolites are often resolved at an appropriate eluent pH. Even analogues differing by a methylene unit in a side-chain remote from a basic centre are often resolved. Applications of Waters Spherisorb S5SCX columns include HPLC of antimalarials such as chloroquine and quinine, cardioactive drugs, for example amiodarone and flecainide, antipsychotics (clozapine, olanzapine), and antidepressants (amitriptyline, clomipramine, dothiepin, fluoxetine) and their N-desalkyl metabolites. Major practical features of these systems are that (i) acidic and neutral compounds are not retained, (ii) solvent extracts can be injected directly, and (iii) eluent recycling can be performed routinely.