Background: Oral fluid is an alternative matrix with potential applications in road-side drug screening, work-place testing, drug treatment programs, and epidemiological surveys. Development of methods for extensive drug screening in oral fluid is warranted. Methods: We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for drug screening of preserved oral fluid collected with the Intercept((R)) collection device. Samples were prepared by liquid-liquid extraction with ethylacetate/heptane (4:1). LC-separation was achieved with an Atlantis dC18-column (2.1 X 50 nun, 3 gm particle). Mass detection was performed by positive ion mode electrospray LC-MS/MS and included the following drugs/metabolites: morphine 6-monoacetylmorphine, codeine, buprenorphine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetimine, 3,4-methylenedioxyethylamphetamine, cocaine, benzoylecgonine, Delta-9-tetrahydrocannabinol, lysergic acid diethylamide, alprazolam, bromazepam, clonazepam, 7-aminoclonazepam, diazepam, N-desmethyldiazepam, 3-OH-diazepam, fenazepam, flunitrazepam, 7-aminoflunitrazepam, lorazepam, nitrazepam, 7-aminonitrazepam, oxazepam, zopiclone, zolpidem, carisoprodol, and meprobamat Results: Screening of 32 drugs was performed with a run time of 14 min. Within- and between-day relative CVs varied from 2.0% to 31.8% and from 3.6% to 39.1%, respectively. Extraction recoveries were > 50% except for morphine (30%) and benzoylecgonine (0.2%). The concentrations of the lowest calibrator were 1 nmol/L (0.28 mu g/L) to 500 nmol/L (68 mu g/L), depending on the drug. Conclusion: The method allowed. rapid and sensitive oral fluid screening for the most commonly abused drugs in Norway and will be used for a road-side survey of drug use in normal traffic. (c) 2007 American Association for Clinical Chemistry