Current Technologies and Considerations for Drug Bioanalysis in Oral Fluid

Abstract

Drug oral fluid analysis was first used almost 30 years ago for the purpose of therapeutic drug monitoring. Since then, oral fluid bioanalysis has become more popular, mainly in the fields of pharmacokinetics, workplace drug testing, criminal justice, driving under the influence testing and therapeutic drug monitoring. In fact, oral fluid can provide a readily available and noninvasive medium, without any privacy loss by the examinee, which occurs, for instance, during the collection of urine samples. It is believed that drug concentrations in oral fluid may parallel those measured in blood. This feature makes oral fluid an alternative analytical specimen to blood, which assumes particular importance in roadside testing, the most published application of this sample. Great improvements in the development of accurate and reliable methods for sample collection, in situ detection devices (on-site drug detection kits), and highly sensitive and specific analytical methods for oral fluid testing of drugs have been observed in the last few years. However, without mass spectrometry-based analytical methods, such as liquid chromatography coupled to mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS/MS), the desired sensitivity would not be met, due to the low amounts of sample usually available for analysis. This review will discuss a series of published papers on the applicability of oral fluid in the field of analytical, clinical and forensic toxicology, with a special focus on its advantages and drawbacks over the normally used biological specimens and the main technological advances over the last decade, which have made oral fluid analysis of drugs possible.

Determination of biomarkers of tobacco smoke exposure in oral fluid using solid-phase extraction and gas chromatography–tandem mass spectrometry

“…This also leads to an increase in sensitivity, and lower amounts of the analytes can be detected [38]. This assumes even more relevance when OF is tested, since the analytes' concentrations are usually low in this specimen [39]. This powerful tool has already been used in bioanalysis, namely in the detection of biomarkers of alcohol consumption [40], in vivo lipid peroxidation [41] or the detection of the metabolite of 9 -tetrahydrocannabinol (carboxy-THC) in hair samples at concentrations in the range of pg/mg [42].…”

Opening the toolbox of alternative sampling strategies in clinical routine: A key-role for (LC-)MS/MS

“…Moreover, even when a correlation is observed, the latter might be time-or concentration dependent and/or intra-and interpatient variability may be too large to allow reliable use in clinical practice 17 . Therefore, oral fluid is probably not suitable for TDM of most therapeutic drugs 96 .…”

“…Another important issue in oral fluid analysis is the fact that analyte levels may depend on a multitude of variables such as compound pKa, molecular weight, charge and lipid solubility, as well as oral fluid pH, flow rate and metabolism 10,16 . Consequently, the measured oral fluid concentrations can be heavily influenced by the employed collection procedure 16,17 . Oral fluid can either be collected without stimulation (e.g.…”

“…Moreover, adsorption may occur to collection devices and -important when sample analysis is to be performed by LC-MS/MS-matrix effects may arise from incorporated buffers, preservatives or surfactants [16][17][18] . Due to the above-mentioned issues, careful selection and standardization of the oral fluid collection procedure is essential to obtain reliable and reproducible results.…”

“…via passive drooling) or with mechanical or chemical stimulation (e.g. by chewing on paraffin or by using citric acid, respectively) 16,17 .…”