Liquid chromatographic determination of diltiazem and its metabolites using trans isomers as internal standards, with dynamic modification of the solid phase by addition of an amine to the mobile phase

A selective and sensitive reversed-phase high-performance liquid chromatographic method for simultaneous analysis of diltiazem and its five metabolites known to occur in man is presented. Different C18 columns are compared. The influences of organic co-solvent, pH, ionic strength and the addition of various amines are studied. The use of trans-diltiazem as internal standard is advocated. UV detection at 237 nm is used for plasma analyses. The possibilities of electrochemical detection are also discussed. Before solvent extraction, plasma samples are saturated with sodium chloride and made alkaline. Triethylamine is also added. The use of the method in pharmacokinetic applications is exemplified.