“…A number of issues in the collection, storage, processing, analysis and use of DBSs have been recognized [7, 10, 12, 13, 18], and most pertain to environmental toxicants. These include: loss of analytes by enzymatic action (or other mechanisms) during the collection, spotting and drying stages [31, 32]; differences between analyte profiles measured using DBS and plasma [33]; effects of storage times and storage conditions on sample integrity [34, 35]; the consistency of blood spot punches and chromatographic considerations on sample cards [36]; variability, recovery, sorption and other issues involved in extracting analytes from sample cards [11, 26, 37]; variability in blood volumes, irregular geometry of the DBS itself, and punch size [8, 38, 39]; background (matrix) contamination on the filter paper [15, 20]; within- and between-lot variability of the sample card properties and contamination [40]; chromatographic, carryover and other separation issues in analysis and quantitation [41]; limited sensitivity of methods, which can be particularly acute given the small volume of sample available [5, 10]; and a lack of standard reference materials (SRMs) to help ensure that measurements meet quality assurance criteria. (For example, SRMs are available from NIST for (persistent) organic contaminants in non-fortified human serum [SRM-1957] and metals in caprine (goat) blood [SRM-955c]).…”