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

The multiple pathological effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and its total novelty, mean that currently a lot of diagnostic and therapeutic tools, established and tentative alike, are needed to treat patients in a timely, effective way. In order to make these tools more reliable, faster and more feasible, biological fluid microsampling techniques could provide many advantages. In this review, the most important microsampling techniques are considered (dried matrix spots, volumetric absorptive microsampling, microfluidics and capillary microsampling, solid phase microextraction) and their respective advantages and disadvantages laid out. Moreover, currently available microsampling applications of interest for SARS-CoV-2 therapy are described, in order to make them as much widely known as possible, hopefully providing useful information to researchers and clinicians alike. 

Quantitative microsampling for bioanalytical applications related to the SARS-CoV-2 pandemic: Usefulness, benefits and pitfalls.

A core-shell AuNRs@Ag-enhanced and magnetic separation-assisted surface-enhanced Raman spectroscopy (SERS) immunosensing platform was developed for rapid, accurate and sensitive detection of amantadine (AMD) contaminant in animal-derived foods. This SERS immunosensing platform works in a competitive strategy, which used the 4-mercaptobenzoic acid (4-MBA) labeled AuNRs@Ag with AMD-BSA immobilized as a signal probe and magnetic beads (MBs) with mAbs covalently attached to the surface as a capture probe. It was found that the synthesized core-shell AuNRs@Ag could significantly enhance the SERS signal of the reporter 4-MBA (EF: 2.91 × 107), and the coating of Ag shell effectively avoided the shedding of 4-MBA, thereby improving the sensitivity and stability of SERS analysis. The use of MBs not only overcomes the shortcoming of mAbs inactivation, but also simplifies the detection procedure, improving the detection efficiency. This SERS immunosensing platform was demonstrated to have a linear response in a wide AMD concentration range of 0.01–50 μg/L with high sensitivity (limit of detection (LOD): 0.0038 μg/L) and specificity. For actual animal-derived foods (chicken, milk, egg), acceptable recoveries of AMD (82.0–106.0%) at three spiked levels (0.5, 5, 50 μg/kg) were obtained with relative standard deviation (RSD, n = 5) ranging from 4.7% to 9.6%. The whole detection procedure can be completed within 30 min. These results demonstrated that the proposed SERS immunosensing platform was reliable and sensitive in the quantitative analysis of AMD and could be applied as an effective tool for rapid screening for AMD-contaminated foods.

Core-shell AuNRs@Ag-enhanced and magnetic separation-assisted SERS immunosensing platform for amantadine detection in animal-derived foods

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.

Biological Fluid Microsampling for Therapeutic Drug Monitoring: A Narrative Review

Amantadine plasma concentrations correlate well with desired therapeutic effects and adverse outcomes; information on amantadine exposure could be useful when multiple amantadine clearance pathways are impaired or non-compliance is suspected. Micro-sampling strategies, like dried plasma spot, would be particularly useful because ambulatory patients that do not attend a clinic can easily sample a few drops of blood by themselves at the required time of the dosing interval. We developed and validated a dried-plasma-spot-based high performance liquid chromatography-tandem mass spectrometry assay to quantify amantadine. This assay met relevant validation requirements within a hematocrit range of 20-50% and was linear from 100 to 2000 ng/mL. Amantadine was stable in dried plasma spots for up to 21 days at room temperature, regardless of whether the dried plasma spot was protected from light or not. The correlation between paired dried and wet plasma concentrations was assessed in 52 patients. Deming regression coefficients between wet plasma and simultaneously pipetted dried plasma spots were used to predict plasma concentrations. Bland-Altman plots revealed a strong agreement between dried and wet plasma concentrations, supporting the clinical usefulness of dried plasma spots for amantadine monitoring with a self-sampling strategy at a convenient time and place for the patient.

Amantadine hydrochloride monitoring by dried plasma spot technique: High-performance liquid chromatography-tandem mass spectrometry based clinical assay.

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Amantadine hydrochloride monitoring by dried plasma spot technique: High-performance liquid chromatography-tandem mass spectrometry based clinical assay.