The primary objective of this proposal is to develop new and innovative analytical methods which are specific and sensitive for pharmacologically and toxicologically active compounds in biologic specimens. Of particular interest in this study are cocaine and its metabolites, melatonin, the tricyclic antidepressants and several of the phenothiazine compounds. The goal will be to develop methodology that will be capable of determining each of these agents in 0.5 to 1.0 ml of serum or whole blood after therapeutic amounts have been ingested, or in the case of cocaine, absorbed through the nasal cavity. By means of gas-liquid chromatography utilizing the electron capture detector it has been demonstrated in our laboratory that most of the drugs listed above can be determined at subnanogram levels. The conditions for derivatization of certain of the drugs in biologic extracts to electron absorbing compounds susceptible to highly sensitive detection by electron capture have been already established in the laboratory of the principal investigator. Similar derivatization of cocaine and (or) its metabolites will be attempted in the proposed project. Analysis of cocaine at the subnanogram level in serum will provide a route to better understanding of the pharmacokinetics and bio-availability of this widely abused drug. Thin-layer chromatographic procedures for screening large numbers of specimens at sensitivity levels to meet the needs of drug rehabilitation programs and law enforcement offices will be accomplished. The need for a rapid, low-cost, urine screening method for cocaine and (or) its metabolites is highly relevant to the drug scene. Significant progress in that direction has been made during the current budget year.