Dried Blood Spots in Toxicology and Antidoping Analyses

Dried Blood Spots in Toxicology and Antidoping Analyses

  • Definition:

    • Dried blood spots (DBS) are drops (10-30 µL) of fresh whole blood that are dried on a paper support such as Whatman paper.

  • History:

    • The use of dried blood spots has been explored since 1976 with extensive applications in various fields.

  • Applications:

    • Therapeutic Drug Monitoring (TDM): Ensuring the correct dosage of medications through monitoring drug levels.
    • Newborn Screening: Early detection of congenital disorders.
    • Doping Controls: Monitoring athletes for banned substances.

  • Advantages:

    • Minimally Invasive: Easier to collect than venous blood.
    • Fast Processing: Rapid collection and analysis.
    • Stable and Robust: Stable products that can be stored easily.
    • Transport: Simple and cost-effective shipping requirements.
    • Accurate: Reflects circulating drug concentrations effectively.

  • Limitations:

    • Hematocrit Effect: Variability in hematocrit levels can affect drug concentration measurements.
    • Sample Size: Small sample volume limits the number of tests that can be performed.
    • Quantitative Analysis: Requires isotopically labeled internal standards (ISTDs) for accurate results.
    • Metabolite Profiles: Established profiles for certain substances may not be readily available, complicating interpretation.

  • Sampling Procedure:

    • Important factors include collection procedure, type of filter paper used, sample volume, the drying process, and the impact of hematocrit.
    • Commonly used papers are pre-treated or untreated types, which impact analyte stabilization and recovery.

  • Current Research:

    • Numerous studies focus on enhancing DBS analysis through electric-field assisted methods and more sensitive detection technologies like mass spectrometry (MS).
    • Advances in methods such as ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) are critical for TDM and other applications.

  • Regulatory Guidelines:

    • Various guidelines exist for the development and validation of DBS methods for clinical applications, emphasizing the need for reliable and reproducible results.

  • Detection of Drugs of Abuse:

    • Studies have detailed the sensitivity and specificity of DBS for detecting various drugs, including narcotics and psychoactive substances, using LC-MS/MS and other analytical techniques.

  • Phosphatidylethanol (PEth):

    • Used as a biomarker for alcohol consumption due to its long half-life and stability in DBS.
    • PEth analysis provides insights into chronic alcohol abuse and can be utilized in various clinical settings.

  • Future Directions:

    • Continued improvement in sampling, storage, and analytical methods will enhance the reliability and applicability of DBS in clinical and forensic toxicology.
    • Emphasis on green analytical chemistry practices to minimize environmental impact while performing accurate tests.

  • Validation Parameters:

    • Key aspects include selectivity, limit of detection, accuracy, precision, robustness, and recovery rates from samples.
    • Validation ensures that methods are suitable for intended use, particularly in clinical and forensic contexts.