Bioanalytical issues in patient-friendly sampling methods for therapeutic drug monitoring: Focus on antiretroviral drugs

Therapeutic drug monitoring is a way to pharmacokinetically guide drug therapy to assure a certain exposure to a drug when this exposure is related to treatment effectiveness or toxicity. Routinely, drug concentrations are measured in plasma obtained by venipuncture. However, venous sampling is difficult in some populations, such as neonates and patients suffering from phlebitis, and there may be logistical challenges, for example when nonhospital-based sampling is warranted (e.g., resource-limited settings). A proper bioanalytical method is crucial for measurements of drug level matrices suitable for patient-friendly drug monitoring. Special attention must be paid to bioanalytical methods in these patient-friendly matrices, since specific matrix-associated issues may have important implications. In this review, we will discuss these issues and give an overview of published bioanalytical methods with a focus on patient-friendly drug monitoring of antiretroviral drugs, where dried blood spots, hair and saliva have been the most important matrices for patient-friendly therapeutic drug monitoring. Furthermore, we will point out considerations for proper assay development and validation.