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Development and application of a novel method to characterize methylmercury exposure in newborns using dried blood spots.

ABSTRACT: BACKGROUND:Methylmercury (MeHg) is a pollutant of global concern. While there is a need to gauge early-life exposures, there remain outstanding ethical, financial, and practical challenges with using the preferred biomarker, whole blood, notably in pregnant women, infants, toddlers, and children. Dried bloodspots (DBS) may help overcome some of these challenges. Notably DBS are collected from newborns in many jurisdictions offering an institutionalized platform to efficiently characterize exposures. OBJECTIVE:To develop, validate, and apply a new method to measure MeHg levels in DBS with a specific aim to use this method to increase understanding of newborn exposures. METHODS:Method development and validation was pursued by consulting U.S. EPA Method 1630 and other resources. The method was applied to measure MeHg levels in DBS from newborns (n = 675) from the Michigan BioTrust for Health program. RESULTS:The assay's detection limit (0.3?g/L), accuracy (96-115% of expected), precision, linearity, and range met performance criteria guidelines. In the newborn DBS samples, the mean (SD) and geometric mean values of MeHg were 1.46 (0.90) and 1.25?g/L respectively, and ranged from 0.09 to 9.97?g/L. The values we report here are similar to cord blood mercury values reported elsewhere. CONCLUSIONS:This is the first characterization of MeHg exposure in newborns, and thus fills an important data gap as prior studies have focused on pregnant women, cord blood, or toddlers. This method helps overcome technical challenges associated with other proposed approaches, and moving ahead there is great promise for applying this DBS-based method for population-level surveillance, particularly in resource-limited settings and for children's health.

SUBMITTER: Basu N

PROVIDER: S-EPMC6309537 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Development and application of a novel method to characterize methylmercury exposure in newborns using dried blood spots.

Basu Niladri N Eng Jenny W L JWL Perkins Marie M Santa-Rios Andrea A Martincevic Gordana G Carlson Krystin K Neitzel Richard L RL

Environmental research 20170818

<h4>Background</h4>Methylmercury (MeHg) is a pollutant of global concern. While there is a need to gauge early-life exposures, there remain outstanding ethical, financial, and practical challenges with using the preferred biomarker, whole blood, notably in pregnant women, infants, toddlers, and children. Dried bloodspots (DBS) may help overcome some of these challenges. Notably DBS are collected from newborns in many jurisdictions offering an institutionalized platform to efficiently characteriz ...[more]

PMID: 28825981

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Project description:BackgroundDolutegravir is currently the preferred component of first-line antiretroviral therapy. To facilitate clinical pharmacology studies in key populations, quantitative analytical methods compatible with microsampling and adaptable to resource-limited settings are desirable. The authors developed and validated a liquid chromatography-ultraviolet detection method to quantify dolutegravir in dried blood spots (DBS).MethodsCalibration standards and quality control samples were prepared by spotting 50 μL of dolutegravir-spiked whole blood on each circle of DBS cards. Three spots (two 6-mm punches/spot) were extracted with methanol. Chromatographic separation was achieved with gradient elution of acetonitrile/potassium phosphate monobasic buffer (pH 5) on a reverse-phase C18 column (flow rate, 1 mL/min) using pioglitazone as the internal standard. UV detection was performed at 260 nm. In the clinical pharmacokinetic study, DBS from finger prick was collected from participants (n = 10) at 8 time points over 12 hours postdosing, with paired plasma at 1 and 12 hours. The method was used to quantify dolutegravir, estimating pharmacokinetic parameters. Agreement between DBS and plasma concentrations was evaluated using linearity and Bland-Altman plots.ResultsThe method was validated over the concentration range of 0.4-10 mcg/mL, accuracy was 102.4%-114.8%, and precision was 3.4%-14.7%. The mean recovery was 42.3% (%CV: 8.3). The mean (±SD) dolutegravir concentration in DBS was 37.5% (±3.8%) lower than that in the plasma. DBS-derived and measured plasma concentrations showed strong correlation with linearity (R2 = 0.9804) and Bland-Altman plots. Means (%CV) of area under curve, Cmax, and C24 from the DBS-derived plasma concentration were 37.8 (23.2) mcg·h/mL, 2.7 (24.7) mcg/mL, and 1.34 (31.6) mcg/mL, respectively.ConclusionsThe application of this simple, accurate, and precise method will expand opportunities for clinical assessment of dolutegravir in resource-limited settings.

Dataset Information

Development and application of a novel method to characterize methylmercury exposure in newborns using dried blood spots.

Publications

Development and application of a novel method to characterize methylmercury exposure in newborns using dried blood spots.

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