Emerging liquid chromatography–mass spectrometry technologies improving dried blood spot analysis

Abstract

Dried blood spots (DBS), a micro blood sampling technique, has recently gained interest in drug discovery and development due to its inherent advantages over the conventional whole blood, plasma or serum sample collection. Since the regulatory authorities have agreed to the use of blood as an acceptable biological matrix for drug exposure measurements, its applications have been extended not only to therapeutic drug monitoring but also to toxicokinetic and pharmacokinetic studies. The pharmaceutical industry is keen to promote DBS as a prominent tool in bioanalytical applications due to the financial, ethical and organizational issues involved in clinical trials. This could be accomplished due to the latest advances in modern analytical technology, particularly liquid chromatography–mass spectrometry. The present review discusses some of the emerging liquid chromatography–mass spectrometry technologies in improving DBS analysis for its innovative applications in the development of new drugs.

Keywords::

• automation
• DBS LC–MS/MS
• dried blood spots
• drug development
• high throughput

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Need for development of new integrated procedures compatible with liquid chromatography–mass spectrometry (LC–MS) for addition of internal standards.

• Since blood is a matrix, variations in hematocrit and its properties may have a huge impact on quantitative dried blood spots (DBS)–LC–MS analysis.

• It is challenging to develop highly sensitive LC with tandem MS methods to achieve pictogram level lower limits of quantification.

• Flinders technology associates cards with different ingredients may have significant impact on DBS analysis.

• Improving the sensitivity limitations of surface sampling techniques, namely, desorption electrospray ionization and direct analysis in real time.

• Optimization of off-line punching and extraction procedures for processing a large number of samples.

• Differences in pharmacokinetics between blood and plasma as matrices.

• Improving the accuracy and precision of various integrated approaches to automate DBS analysis.