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. 2016 Dec 1;27(4):288-317.
eCollection 2016 Dec.

Advantages and Challenges of Dried Blood Spot Analysis by Mass Spectrometry Across the Total Testing Process

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Advantages and Challenges of Dried Blood Spot Analysis by Mass Spectrometry Across the Total Testing Process

Rosita Zakaria et al. EJIFCC. .

Abstract

Introduction: Through the introduction of advanced analytical techniques and improved throughput, the scope of dried blood spot testing utilising mass spectrometric methods, has broadly expanded. Clinicians and researchers have become very enthusiastic about the potential applications of dried blood spot based mass spectrometric applications. Analysts on the other hand face challenges of sensitivity, reproducibility and overall accuracy of dried blood spot quantification. In this review, we aim to bring together these two facets to discuss the advantages and current challenges of non-newborn screening applications of dried blood spot quantification by mass spectrometry.

Methods: To address these aims we performed a key word search of the PubMed and MEDLINE online databases in conjunction with individual manual searches to gather information. Keywords for the initial search included; "blood spot" and "mass spectrometry"; while excluding "newborn"; and "neonate". In addition, databases were restricted to English language and human specific. There was no time period limit applied.

Results: As a result of these selection criteria, 194 references were identified for review. For presentation, this information is divided into: 1) clinical applications; and 2) analytical considerations across the total testing process; being pre-analytical, analytical and post-analytical considerations.

Conclusions: DBS analysis using MS applications is now broadly applied, with drug monitoring for both therapeutic and toxicological analysis being the most extensively reported. Several parameters can affect the accuracy of DBS measurement and further bridge experiments are required to develop adjustment rules for comparability between dried blood spot measures and the equivalent serum/plasma values. Likewise, the establishment of independent reference intervals for dried blood spot sample matrix is required.

Keywords: dried blood spots; mass spectrometry; total testing process.

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Figures

For a fixed punch size, a high level of Hb/Hct results a higher amount of blood on the punch thus the measured target analyte is falsely elevated. This figure is a visual demonstration of the effect of haematocrit on diffusion.
Figure 1
Whole blood samples with different levels of haemoglobin/haematocrit (Hb/Hct) do not diffuse similarly on the collection card
Figure 2
Figure 2
Dried blood spot sample analysis process flowchart for mass spectrometric analysis

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