Method improvements for blood lead analysis in dried blood spot (DBS) formats

摘要

Trace analysis for lead (Pb) in dried blood samples is an attractive method for reducing costs in lead monitoring programs for public health. Two major contributors to measurement variance in blood lead concentrations were addressed in an NIEHS funded program at GE Global Research. Methods are described that reduce lead contamination in the sampling matrix and mitigates variability in original sample volume determination. A simple washing procedure for reducing lead contamination in sample collection matrices yields materials with Pb concentrations less than 0.3 ng/g. The extremely low levels of Pb allow detection down to 0.1 μg/dL in extracted caprine blood standards. Despite good method capability, the actual detection limit for samples prepared outside of a cleanroom setting was 7.0 μg/dL due to trace environmental contamination. The environmental background interfered with nearly half of the CDC recommended working range and highlights a challenge associated with DBS methodology that does not impact venous blood samples. Determining initial sample volume is critical for a quantitative Pb assay. A multivariate model for estimating sample volumes from measurements of spot area, mass, and potassium concentration was developed with a prediction accuracy of 5.2 ± 4.2% at 95% confidence. The model was used to reduce the variability from unmetered, or poorly metered, sample collection and was found to reduce the CV in the final measurement to 15 %. A demonstration of the method on a multipatient cohort and a discussion of additional development needs are described.