This research project is designed to investigate the role of saliva as an alternative biological fluid for the quantitative measurement of cocaine and its metabolites. Specimen collection is based on an osmotic device for the collection of an ultrafiltrate of saliva in the mouth. The studies will provide a model for investigations of other drugs of abuse in an ultrafiltrate of saliva. Preliminary results obtained in Phase I of the study demonstrated the feasibility of screening for cocaine and its metabolite, benzoylecgonine, in saliva if the drug was ingested within 24 h of sample collection. During Phase II, sample collection will be expanded to determine how long cocaine use can be detected using an ultrafiltrate of saliva. At the same time, analytical methods will be developed that focus on the lower concentration of analytes and the relatively small sample volume available with saliva as sample medium. These methods will include immunochemical screening procedures and confirmatory analysis by GC/MS or LC/MS. We will investigate whether the ratio of different cocaine metabolites in saliva can be used to obtain additional information about the time of drug ingestion. The refined analytical methods will be used to make an attempt to suggest threshold levels in saliva to determine recent use. The established criteria will be tested in a mixed population of drug users and non-users by comparing urinary concentrations of cocaine and benzoylecgonine with those in saliva.