In this context, an attractive technique to overcome the conventional venous sampling limits and simplify TDM application is represented by dried blood spot (DBS). Lastly, the applicability and feasibility of performing TDM using microsamples in a real-life home-sampling context is discussed.Īnticancer 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. The various impacts of deviating hematocrit values on quantitative results are discussed in a separate section as this is a key issue and undoubtedly the most widely discussed issue in the analysis of dried blood microsamples. We focus on sample preparation, analytics, internal standards, dilution of samples, external quality controls, dried blood spot specific validation parameters, stability and blood-to-plasma conversion methods. Different methodological aspects of microsampling-based methods are discussed and applied to TDM of TKIs. Despite the many advantages associated with dried blood microsampling, quantitative analyses are also associated with some specific difficulties. In this review we focus on the different dried blood microsample-based methods that were used for the quantification of TKIs. Additionally, working with dried matrices improves compound stability, resulting in convenient and cost-effective transport and storage of the samples. The collection of small sample volumes is especially relevant for use in pediatric populations or in pharmacokinetic studies. Collection of samples via finger-prick is minimally invasive and considered convenient and simple, enabling sampling by the patients themselves in their home-setting. The use of dried blood microsamples can overcome these limitations. However, the use of plasma poses some challenges related to sampling and stability. Plasma, obtained via traditional venous blood sampling, is the standard matrix for TDM of TKIs. Moreover, most of the available TKIs are susceptible to various drug-drug interactions and medication adherence can be checked by performing TDM. TKIs are perfect candidates for TDM as they show a relatively small therapeutic window, a wide inter-patient variability in pharmacokinetics and a correlation between drug concentration and effect. Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) is not yet performed routinely in the standard care of oncology patients, although it offers a high potential to improve treatment outcome and minimize toxicity. EPC: Estimated plasma concentration Hct: Hematocrit IM: Imatinib. Dashed lines indicate IM target concentrations in plasma to therapeutic drug monitoring (1000 ng ml -1 ) and proposed IM concentration target. (C) (i) Bland and Altman plot comparing IM EPC calculated from DBS levels and correction factor with measured plasma concentrations (ii) correlation between EPC calculated from DBS levels and correction factor and measured plasma concentrations. (B) (i) Bland and Altman plot comparing IM EPC calculated from DBS levels and Hct with measured plasma concentrations (ii) correlation between EPC calculated from DBS levels and correction factor and measured plasma concentrations. (A) (i) Bland and Altman plot comparing IM concentrations in DBS with measured plasma concentrations (ii) correlation between IM concentrations in DBS and measured plasma concentrations. Comparison of imatinib concentrations in DBS and concentrations in plasma estimated from dried blood with measured concentrations in plasma in clinical samples.
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