Determination of vitamin D and its metabolites using capillary dried blood microsampling: are we there yet?

Dried blood microsampling presents a promising alternative to conventional venous sampling for the quantification of 25-hydroxyvitamin D (25-(OH)D), the established biomarker for assessing vitamin D (vit D) status. Its minimally invasive nature, ease of collection and simplified logistics render microsampling particularly attractive for large-scale epidemiological research employing home-based or remote sampling. Performing such studies is increasingly relevant, as a multitude of diseases have been linked to an inadequate vit D status and, thus, more epidemiological biomarker data are needed to further assess its potential impact. While issues related to the analytical sensitivity and specificity of dried blood microsampling for 25-(OH)D determination have been recognized and addressed to a large extent in literature, several important practical and methodological challenges still hinder broader implementation of this technique. Following an overview of the currently available liquid chromatography-tandem mass spectrometry-based methods for the dried blood-based analysis of 25-(OH)D, this review highlights key remaining pitfalls, including (i) the evaluation of a method's robustness, (ii) challenges related to the interpretation of 25-(OH)D results derived from dried blood microsamples, and (iii) the current lack of specific dried blood microsampling-based standardization programs for 25-(OH)D. Understanding and addressing these knowledge gaps is crucial to ensure the reliability and interpretability of 25-(OH)D measurements obtained via dried blood microsampling.