A review of recent advances in microsampling techniques of biological fluids for therapeutic drug monitoring

Conventional sampling of biological fluids often involves a bulk quantity of samples that are tedious to collect, deliver and process. Miniaturized sampling approaches have emerged as promising tools for sample collection due to numerous advantages such as minute sample size, patient friendliness and ease of shipment. This article reviews the applications and advances of microsampling techniques in therapeutic drug monitoring (TDM), covering the period January 2015 - August 2020. As whole blood is the gold standard sampling matrix for TDM, this article comprehensively highlights the most historical microsampling technique, the dried blood spot (DBS), and its development. Advanced developments of DBS, ranging from various automation DBS, paper spray mass spectrometry (PS-MS), 3D dried blood spheroids and volumetric absorptive paper disc (VAPD) and mini-disc (VAPDmini) are discussed. The volumetric absorptive microsampling (VAMS) approach, which overcomes the hematocrit effect associated with the DBS sample, has been employed in recent TDM. The sample collection and sample preparation details in DBS and VAMS are outlined and summarized. This review also delineates the involvement of other biological fluids (plasma, urine, breast milk and saliva) and their miniaturized dried matrix forms in TDM. Specific features and challenges of each microsampling technique are identified and comparison studies are reviewed.