Two methods for the high performance liquid chromatographic analysis
of basic drugs have been studied. In each case the methods have
concentrated on separating drugs of forensic interest, based on specially
designed test solutions of analytes selected to represent most of the
commonly encountered classes of drug compounds.
In the first case, a HPLC method was developed on unmodified silica
using an aqueous methanolic eluent of high pH. The buffer was prepared
from two organic sulphonic acid amines, 3-(cyclohexylamino)-1-
propanesulphonic acid (CAPS) and sodium 3-(cyclohexylamino)-2-hydroxy-1-
propanesulphonate (CAPSO-Na). The method was shown to be highly
reproducible within a single laboratory. The long term stability of the
unmodified silica stationary phase was examined, using the newly developed
method for the analysis of drugs as a monitor of column performance.
Three columns from a single batch of silica were studied, and all showed
pronounced changes in retention properties over the period of the study.
Similar changes in retention properties were observed for silica stored
dry and unused. These results led to the idea that an 'aging process' was
changing the nature of the silica surface, probably by a process of
hydrolysis of surface siloxanes. This aging process was also believed to
be responsible for the appearance of distorted peak shapes for
methylamphetamine, although no clearly defined mechanisms could be found
to support this idea.
In a second study, the application of gradient HPLC methods for the
screening ·of a wide range of analytes was examined. In this case, an
Inertsil ODS-2 column was used in conjunction with an acid buffered
acetonitrile I water gradient. The usefulness of the 1-nitroalkanes as a
retention index series was demonstrated and a good level of retention
reproducibility was achieved for most analytes studied.
A Doctoral Thesis. Submitted in partial fulfillment of the requirements for the award of Doctor of Philosophy of Loughborough University.