A major objective of this proposal is to continue the development within our laboratory of specific and highly sensitive analytical methods for determining many of the polyaromatic drugs in small amounts of sera ( less than 50 ml). The limited number of analytical techniques currently available for analysis of many of the alkaline drugs which are active therapeutically at nanogram concentrations is indicative of the problems associated with the determination of the compounds particularly in small volumes of serum. Gas-liquid chromatography using elctron-capture, nitrogen-phosphorus and photoionization specific detectors will be utilized as a mechanism for development of the new innovative procedures. High performance liquid-liquid chromatography will be applied to the analysis of those polyaromatic drugs that are too polar for effective analysis by gas-liquid chromatography, particularly drug metabolites. The procedures to be developed will utilize internal standards particularly durg metabolites. The procedures to be developed will utilize internal standards that very closely parallel the chemical structure of the drugs to be measured. Drugs for which specific analytical methods will be developed include the tricyclic antidepressants and several of the phenothiazine compounds. The methods will be applicable for utilization both by therapeutic drug monitoring as well as clinical and forensic toxicology laboratories. In addition correlaton studied between saliva and blood concentrations will be initiated to evaluate the practical applicability of saliva concentrations in therapeutic efficacy.