Analytical methods using high performance liquid chromatography, with ultra-violet, electrochemical or fluorescent detection, were developed for the meaurement of (1) of amides and esters of cholorambucil an anticancer agent; (2) amino acids in brain tissue; (3) catacholamines and their metabolites in cerebrospinal fluid (CSF) and plasma; (4) amphotercin B in plasma and brain; (5) polyols in cerebrospinal fluid and plasma. A gas chromatographic-mass spectrometric procedure was developed to measure flurazepam (Dalmane) and its metabolites, M1-desalkyl flurazepam and M1-hydroxyethyl flurazepan. The long term accumulation of N1-desalkyl flurazepam in the cat brain, after administration of flurazepam, probably explains hangover and long term neurotoxicity of this sleep medicine in the elderly. A model was developed to interpret drug binding to plasma proteins as regulating the rate of drug entry into brain from blood.
