Saliva as an alternative specimen to plasma for drug bioanalysis. A review

• Compared to blood, saliva non-invasive sampling.
• Saliva is easy to collect and handle.
• Saliva provides a suitable medium for screening and determination of drugs.
• Present review focuses on the developments and challenges in testing of drugs in saliva in correlation to plasma.

Saliva provides a suitable medium for screening and determination of drugs. It is easy to collect and handle besides the non-invasive sampling. Extraction techniques such as micro-extraction by packed sorbent (MEPS) and dried saliva spot (DSS) provides fast and efficient recovery of the analytes. Moreover, MEPS could be fully automated to ascertain method reproducibility and DSS provides fast simultaneous collection and extraction of samples. Several studies were conducted to determine drugs in saliva in correlation to plasma aiming to establish rigid evidence on the suitability of saliva in monitoring of drug levels. Only free drug could be present in salivary fluid thus protein binding of drugs affect markedly on the salivary levels of drugs. Pharmacokinetic parameters could be determined for drugs in saliva with emphasis on diffusion parameters of drugs to salivary fluid such as pH and drug lipophilicity. Screening techniques are mainly based on mass spectrometry (MS) with an emphasis on Liquid Chromatography-Mass Spectrometry (LC-MS), due to limited sample volumes and the low detection limits. Saliva could make drug testing outside laboratory environments feasible with the appropriate techniques for analysis. This review focuses on the developments and challenges in testing of drugs in saliva in correlation to plasma and application to drug analysis in saliva regarding therapeutic drug monitoring and pharmacokinetics.

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