The use of oral fluid (OF) as an alternative matrix for the detection of drugs of abuse has increased continuously over the last decade. Both the need for a non-invasive sampling method (e.g. at the roadside), advances in our knowledge of toxicokinetics and in analytical capabilities have contributed.

Based on the author's own experience and work and on recent literature data, an overview will be given of the current state-of-the-art.

Drugs are present in oral fluid due to contamination after oral intake, passive diffusion, active secretion and filtration. For basic drugs, the concentration is much higher in OF than in blood, because the drugs are trapped in OF. For acidic drugs, the concentrations are much lower in OF than in blood. The increasing popularity of OF can be explained by some problems with urine testing like the need for supervised sampling and the risk of adulteration. The advantages of OF are the easy supervised sampling, less potential for adulteration, a shorter detection window that correlates better with the (impairing) effect. The unchanged drug is present in oral fluid, often in higher concentration than the metabolites. Sampling of OF can be performed by different procedures (spitting in a tube or by using a device) and nowadays it is well known that the drug concentrations in oral fluid depend on the collection method. For instance, Δ9-tetrahydrocannabinol (THC) binds to the cotton used for sampling, which can cause false negative results. While obtaining a 1mL OF sample is relatively easy and quick in normal subjects, it is more difficult in drug users, who often have a dry mouth due to the effects of the drug. The detection time of most drugs in OF is between 8 and 48 hours, but it depends on the dose and the sensitivity of the assay. Due to large inter-individual variation seen in the OF/blood drug concentration ratios, the drug findings in an OF sample should not be directly used to estimate the concentration of drugs in blood. Onsite testing for drugs in OF has been developed since the nineties, but progress has been slow. While most tests have good specificity, the sensitivity of some onsite tests is still poor, particularly for cannabis, although one test can now reliably detect 5μg/L of THC. In the laboratory, drugs can be screened by ELISA and homogeneous immunoassays. For confirmation, GC-MS and LC-MS/MS are used. The advantage of LC-MS/ MS is that a multi-analyte method is easier to implement. Roadside OF testing to detect drugged driving has already been introduced in the legislation of some countries such as several Australian states, Belgium, France, Spain, Switzerland, and the UK. Oral fluid is also increasingly used in workplace drug testing, with existing guidelines in Australia and New Zealand, and draft guidelines in Europe and the USA. A study in employees of the private sector has shown that the percentage of positive cases with saliva testing (5.1 %) is not different from that obtained with urine testing. Further research needs are studies on passive smoking and external contamination, adulteration and THC washout from the mouth, reproducibility of multiple sampling, the relationship between oral fluid drug concentrations and impairment or crash risk.

The last decade has seen a lot of progress in our ability to analyse drugs in OF and to interpret the results. One can expect that the use of OF drug testing will further increase in the future.