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Abstract INTRODUCTION:
Lead is a toxic metal associated with irreversible neurodevelopmental damage. Children are particularly at risk due to rapid development, increased gastrointestinal absorption, and an underdeveloped blood–brain barrier, making early detection and intervention critical. Blood lead testing is recommended during early childhood, typically at 12 and 24 months of age. Venous whole blood analyzed by inductively coupled plasma mass spectrometry (ICP-MS) is the reference standard for lead measurement. However, venipuncture (VP) is not always feasible due to practical challenges in pediatric sampling. Therefore, low-volume sampling strategies are needed. Dried blood spots (DBS) obtained via capillary collection offer a minimally invasive alternative suitable for decentralized testing. ICP-MS provides the analytical sensitivity required for trace metal quantification from limited-volume specimens, enabling evaluation of capillary DBS for lead measurement. This study compares capillary DBS and venous whole blood analyzed by ICP-MS.
METHODS:
Whole blood from normal donors (n = 31) was collected via VP into EDTA trace metal–free tubes, and in parallel, capillary blood was obtained via fingerstick and applied to Capitainer® filter paper devices (10 µL per spot). An additional 20 residual stored whole-blood samples with previously measured lead concentrations within the analytical measuring interval (AMI: 1–200 µg/dL) were also applied to the filter paper devices, extracted, and analyzed for lead. VP samples were prepared using a 1:50 dilution with 10 µM EDTA diluent, while DBS samples were extracted with 0.01% Triton X-100, followed by 1% hydrochloric acid solution, and diluted [1:100] prior to analysis. Lead concentrations were quantified using a PerkinElmer NexION inductively coupled plasma mass spectrometer (ICP-MS). Differences between VP and DBS-derived lead concentrations were calculated as [LeadVP] − [LeadDBS], and agreement was evaluated using a pre-defined acceptance criterion of ±1.45 µg/dL.
RESULTS:
At the medical decision point (3.5 µg/dL), DBS specimens demonstrated within-run precision of 3.9% CV and interlaboratory precision of 5.8% CV. Venous samples from normal donors were below the lower limit of quantitation (LLOQ, <1.0 µg/dL), with corresponding capillary DBS samples also below the LLOQ. Twenty residual whole-blood specimens spanning 3.5–49.6 µg/dL were evaluated. Following application to Capitainer® devices and extraction, DBS samples showed a median lead concentration of 6.5 µg/dL (IQR: 13.7 µg/dL). Compared to the corresponding venous reference measurements, DBS demonstrated minimal bias (mean ± SD: −0.002 ± 0.445 µg/dL), with a mean percent difference of −0.3% (SD: 4.0%) and a mean absolute percent difference of 2.9%.
DISCUSSION:
Capillary DBS sampling demonstrated strong agreement with venous whole blood ICP-MS for lead, with minimal bias (−0.002 µg/dL; −0.3%) and low variability across a clinically relevant range. DBS demonstrated within-run and between-run precision of 3.9% and 5.8% CV, respectively. The achieved precision supports reliable classification near lead’s clinically actionable threshold, where small analytical variation could influence follow-up and intervention decisions. Although prospectively collected donor samples were below the lower limit of quantitation (<1.0 µg/dL), residual specimens (original venous lead concentrations 3.5–49.6 µg/dL) enabled evaluation across clinically relevant and elevated concentrations. Across this range, DBS results closely matched reference venipuncture measurements, demonstrating accuracy and reproducibility of the collection method. These findings support DBS microsampling coupled with ICP-MS as a reliable low-volume alternative to venipuncture for trace metal analysis and may improve pediatric screening feasibility, enabling earlier detection of lead exposure and earlier clinical intervention.
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= Discovery stage. (57.21%, 2026)
= Translation stage. (23.38%, 2026)
= Clinically available. (19.40%, 2026)
