Dried Blood Spot Technique Applied in Therapeutic Drug Monitoring of Anticancer Drugs: a Review on Conversion Methods to Correlate Plasma and Dried Blood Spot Concentrations

Abstract

Background Anticancer drugs are notoriously characterized by a low therapeutic index, the introduction of therapeutic drug monitoring (TDM) in oncologic clinical practice could therefore be fundamental to improve treatment efficacy. In this context, an attractive technique to overcome the conventional venous sampling limits and simplify TDM application is represented by dried blood spot (DBS). Despite the significant progress made in bioanalysis exploiting DBS, there is still the need to tackle some challenges that limit the application of this technology: one of the main issues is the comparison of drug concentrations obtained from DBS with those obtained from reference matrix (e.g., plasma). In fact, the use of DBS assays to estimate plasma concentrations is highly dependent on the chemical-physical characteristics of the measured analyte, in particular on how these properties determine the drug partition in whole blood. Methods In the present review, we introduce a critical investigation of the DBS-to-plasma concentration conversion methods proposed in the last ten years and applied to quantitative bioanalysis of anticancer drugs in DBS matrix. To prove the concordance between DBS and plasma concentration, the results of statistical tests applied and the presence or absence of trends or biases were also considered.

A rapid and sensitive ultra‐performance liquid chromatography tandem mass spectrometry method for determination of anlotinib in plasma and dried blood spots: Method development, validation, and clinical application

“…16,19,20 sampling offers a great opportunity to overcome these problems, as patients themselves can collect their blood on a filter paper card at home using a simple finger prick and post the dried sample to clinical center for analysis. 22,23 Moreover, the DBS method is less invasive and requires lower blood volume than traditional blood sampling. As the drugs are typically stable in the dried matrix, DBS cards can be stored and transported at room temperature.…”

“…As the drugs are typically stable in the dried matrix, DBS cards can be stored and transported at room temperature. 22,23 Therefore, DBS sampling is a viable alternative method to conventional venous sampling for TDM.…”

“…Moreover, considering the global pandemic of coronavirus disease 2019 (COVID‐19), patients and clinicians are at the risk of being exposed to the virus during sample collection, as conventional blood sampling requires a trained phlebotomist to collect venous blood 21 . Dried blood spot (DBS) sampling offers a great opportunity to overcome these problems, as patients themselves can collect their blood on a filter paper card at home using a simple finger prick and post the dried sample to clinical center for analysis 22,23 . Moreover, the DBS method is less invasive and requires lower blood volume than traditional blood sampling.…”

A rapid, simple and sensitive LC-MS/MS method for lenvatinib quantification in human plasma for therapeutic drug monitoring

“…Thus, the development of a LC-MS/MS method based on DBS matrix could be of considerable interest in this context. The proposed method can be used as reference assay to clinically validate the DBS-based method [ 20 ].…”

Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors Using Dried Blood Microsamples

“…In literature, dried blood TKI concentrations were converted to plasma concentrations based upon approaches that take into account a Hct correction, with or without considering the influence of blood-to-plasma partitioning of the TKI, or directly via empirically obtained regression equations or correction factors. When applying such experimentally determined correction factor or regression, it is essential that this is validated on an independent dataset which was not used for deriving that factor ( 80 ). Nilotinib plasma concentrations derived from capillary DBS concentrations were calculated, taking into account the Hct and the blood-to-plasma ratio using the formula described by Wilhelm et al ( 30 ).…”