A New Ultraperformance–Tandem Mass Spectrometry Oral Fluid Assay for 29 Illicit Drugs and Medications

Abstract

Oral fluid (saliva) testing—including the numbers of tests, the analytical procedures used, and laboratories offering the service—is increasing rapidly throughout Europe, North America, and Australia (1)(2). Although the monitoring of therapeutic drugs in oral fluid offers a noninvasive means of estimating the free concentrations of drugs in plasma or serum, this technique is used infrequently (3). There currently is great interest in the use of this alternative matrix for documenting driving under the influence of drugs (DUID)1 and for workplace and drug-treatment testing. Oral fluid can be collected under direct observation without requiring same-sex collectors and specialized collection facilities, and its use reduces the opportunities for sample adulteration. Weak bases are ion-trapped in oral fluid because of its lower pH, yielding higher concentrations and easier detection than in blood. The risk to analysts of infectious-disease exposure is lower than for blood, and the presence of the parent drug in oral fluid may provide a better correlation with ongoing pharmacodynamic effects than with urine testing (4). Oral fluid also offers improved identification of heroin use because of the frequent presence of 6-acetylmorphine and even heroin itself, whereas this biomarker has a short window of detection in urine (5). Oral fluid testing also has disadvantages (6), as for any biological matrix. The volume of oral fluid is limited and may be reduced by drug consumption. Drug concentrations in oral fluid also are lower than in urine (e.g., benzodiazepines and cannabinoids), and their measurement therefore requires highly sensitive assays. Inhalation, smoking, oral, or insufflation administration may contaminate the oral mucosa, increasing concentrations and disrupting correlations with blood results. Another disadvantage is that excretion and concentrations vary with the pH of oral fluid given that the pH increases with the stimulation of oral fluid flow. Yet another limitation is the …