Controlling the retention of clopenthixol and other basic drug substances by reversed-phase ion-pair chromatography on bonded-phase materials using two counter-ions of opposite charge.

In the reversed-phase chromatography of nitrogen-containing bases on chemically bonded ODS-silica, peak tailing and prolonged retention are often considerable problems. These effects are due to residual silanols on the surface of the column material and may be remedied by adding suitable amines or quaternary ammonium ions to the eluent as anti-tailing agents. However, further addition of an anionic compound is often needed to achieve a suitable retention. The retention mechanism in such systems is complex as interaction takes place between the anionic compound and the solute molecules, anti-tailing agent and column packing material. The influence of the nature of the anti-tailing agent and anionic counter-ion on the retention of cis- and trans-clopenthixol and of other basic drug substances was investigated and it was found that both the retention and the selectivity were greatly affected.

Separation of basic drug substances by reversed-phase high-performance liquid chromatography on dynamically modified silica and on bonded-phase materials.

The chromatographic behaviour in the reversed-phase mode of various drug substances, which are nitrogen-containing bases, has been investigated. Three different types of column materials were used, ordinary chemically bonded ODS-silica, deactivated ODS-silica specifically designed for the separation of bases and bare silica dynamically modified by adding long-chain quaternary ammonium compounds to the eluent. Various brands were tested for all three types of column materials. When using ODS-silica as the column material, considerable tailing of peaks and prolonged retention was observed. Also the deactivated columns exhibited tailing problems, but less pronounced. For both types of bonded-phase material it was possible to reduce the tailing considerably by the addition of an anti-tailing agent to the eluent. On bare silica used in the dynamic modification mode the tailing was almost negligible.

Separation of corticosteroids by high-performance liquid chromatography on dynamically modified silica.

High-performance liquid chromatographic methods have been elaborated for the separation of 12 different corticosteroids by reversed-phase chromatography on bare silica, dynamically modified by cetyltrimethylammonium bromide added to the eluent. The selectivity of the systems towards a mixture of the 12 corticosteroids and towards a mixture of hydrocortisone and its related impurities were investigated using different brands of silica. The variations in selectivity were found to be substantially smaller than those of chromatographic systems based on chemically bonded ODS-silicas from the same sources.

Dynamically-modified silica--an alternative to reversed-phase high-performance liquid chromatography on chemically bonded phases.

An alternative to the well known reversed-phase separations on chemically-bonded phases has been developed. The approach is based on a dynamic modification of bare silica with long chain quaternary ammonium ions. The influence of the concentration and type of the quaternary ammonium ion, the pH value and the ionic strength of the eluent on the selectivity towards test solutes has been investigated. The large number of parameters that can be varied in the system offers numerous possibilities by which the desired selectivity can be attained. Once established, a high degree of reproducibility of the selectivity between solutes is obtained even when using different brands of silica; this is in contrast to the situation when using chemically-bonded phases, such as, for example, different brands of octadecylsilyl-bonded silica materials.

Determination of impurities in propranolol hydrochloride by high-performance liquid chromatography on dynamically modified silica.

A rapid high-performance liquid chromatographic method has been elaborated for the separation and determination of small amounts of impurities in propranolol hydrochloride. The separation was achieved on a column of bare silica (Zorbax SIL) with methanol-water-0.2 M phosphate buffer pH 8.0 (70:25:5) containing 2.5 mM of cetyltrimethylammonium (CTMA) bromide as the eluent. The concentrations of methanol and CTMA as well as the pH of the phosphate buffer were found greatly to affect the separation. The selectivity of the system towards a mixture of propranolol and three possible impurities was investigated using different brands of silica. Only minor variations were found relative to those of a chromatographic system based on chemically bonded ODS silicas from the same sources. The method is also suitable for identification purposes, being able to separate most beta-blocking drugs of structures similar to that of propranolol.