December 2012

ith the aging population and recognition that treatment of a patient’s pain is a key healthcare objective, more patients are taking pain medications that must be taken consistently to be effective. But at the same time, many of these same medications are subject to abuse. These benefits and dangers drive the need to test for patient compliance. Although urine has historically been the specimen of choice for this testing, oral fluid is an increasingly attractive alternative. A growing body of literature documents its scientific basis, and advances in liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis are now enabling routine use of oral fluid. Researchers prefer the term oral fluid over saliva because oral specimens include a mixture of saliva and other constituents in the mouth. In addition to the three major salivary glands, other minor glands in the oral mucosa also produce fluids (1). Salivary glands are highly perfused with nutrients from blood, and drugs primarily enter saliva by passive diffusion through cell membranes; thus, drugs in oral fluid reflect free drug circulating in blood. For diffusion to occur, the drugs must be nonionized and have some degree of both lipid and water solubility. Conditions that affect a drug’s excretion into oral fluid include the extent of its plasma-protein binding (bound drug cannot readily diffuse into oral fluid), its dissociation constant (pKa), and the pH of the oral fluid and blood (1,2). Oral fluid is typically more acidic than blood; consequently, weakly basic drugs (such as amphetamines, opioids, and cocaine) may be detected at higher concentrations in oral fluid than blood due to an ion-trapping effect (2). Drug Detection and Prevalence in Oral Fluid