Measurement of xenobiotics in saliva: is saliva an attractive alternative matrix? Case studies and analytical perspectives.

The use of saliva for measuring xenobiotic concentrations has been practiced for a number of years. While the use of saliva has been generally reserved for the analysis of diagnostic and forensic/toxicology samples, attempts have been made to further enhance the value of saliva as an alternate matrix to those of plasma and serum. It is understood that saliva represents a handy tool for therapeutic drug monitoring (TDM) as it offers certain distinctive advantages. This scope of this review encompasses the following: (a) a comprehensive view of saliva as an alternate matrix for either plasma or serum to understand the pharmacokinetic/pharmacodynamic (PK/PD) characteristics; (b) an account of the factors contributing to the observed variability in salivary monitoring; (c) a tabular compilation of diverse case studies of xenobitoics belonging to different therapeutic classes with emphasis on assay methodology and applicable analytical/biopharmaceutical/pharmacokinetic findings; (d) relevant thoughts on assay procedures as they relate to salivary monitoring; and (e) some representative case studies highlighting the new thinking on the use of saliva outside of traditional TDM. Overall, based on the review, saliva represents a valuable TDM tool for a number of xenobiotics. While parent compound and phase I metabolite(s) for many xenobiotics have been generally quantifiable in saliva, phase II metabolites have not generally been detected in saliva. Therefore saliva samples could also be used to answer some specific PK/PD questions during the drug development process, if applicable. However, the development and validation of the assay in saliva needs to be carried out carefully with particular focus on proper sample collection, processing and storage to ensure the stability of the xenobiotics and with the same rigor as applied to plasma, serum and urine matrices.