Biological Fluid Microsampling for Therapeutic Drug Monitoring: A Narrative Review

Abstract

Therapeutic drug monitoring (TDM) is a specialized area of laboratory medicine which involves the measurement of drug concentrations in biological fluids with the aim of optimizing efficacy and reducing side effects, possibly modifying the drug dose to keep the plasma concentration within the therapeutic range. Plasma and/or whole blood, usually obtained by venipuncture, are the “gold standard” matrices for TDM. Microsampling, commonly used for newborn screening, could also be a convenient alternative to traditional sampling techniques for pharmacokinetics (PK) studies and TDM, helping to overcome practical problems and offering less invasive options to patients. Although technical limitations have hampered the use of microsampling in these fields, innovative techniques such as 3-D dried blood spheroids, volumetric absorptive microsampling (VAMS), dried plasma spots (DPS), and various microfluidic devices (MDS) can now offer reliable alternatives to traditional samples. The application of microsampling in routine clinical pharmacology is also hampered by the need for instrumentation capable of quantifying analytes in small volumes with sufficient sensitivity. The combination of microsampling with high-sensitivity analytical techniques, such as liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), is particularly effective in ensuring high accuracy and sensitivity from very small sample volumes. This manuscript provides a critical review of the currently available microsampling devices for both whole blood and other biological fluids, such as plasma, urine, breast milk, and saliva. The purpose is to provide useful information in the scientific community to laboratory personnel, clinicians, and researchers interested in implementing the use of microsampling in their routine clinical practice.

Revolutionizing Blood Collection: Innovations, Applications, and the Potential of Microsampling Technologies for Monitoring Metabolites and Lipids

“…A mixture of acetonitrile and water is a potential extraction solution for hemaPEN ® devices. According to Nix et al, the fundamental benefit of microsampling with hemaPEN ® consists of the fact that sampling can be carried out efficiently and conveniently at the training site [ 9 ]. Although numerous studies demonstrating metabolomic changes during or after physical activity have already been published [ 56 ], none allowed athletes to collect blood by themselves at the training site [ 18 ].…”

“…The compatibility of blood microsampling with various bioanalytical techniques, including mass spectrometry (MS), and enzyme immunoassays [ 6 ], has spurred increased research activity. Applications range from diagnostics and large-scale screenings in clinical studies to drug testing [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ], forensic toxicology [ 17 ], and sports-related analyses [ 18 ]. The integration of MS-based analysis has opened avenues in omics sciences, including metabolomics [ 19 ], proteomics [ 20 ], and lipidomics [ 21 ].…”

Review of the pharmacokinetics of French maritime pine bark extract (Pycnogenol®) in humans

“…Saliva is a biofluid suitable for determination of drug concentrations as an alternative or addition to blood sampling via venipuncture. Typically, it is considered to be an ultrafiltrate of serum containing the free, non-protein-bound fraction of an active molecule ( 68 , 69 ). Until recently, it was not known whether dietary polyphenols circulating in blood would be transferred into saliva.…”