Letter pubs.acs.org/ac
A Robust Method for Iodine Status Determination in Epidemiological Studies by Capillary Electrophoresis Adriana Nori de Macedo,† Koon Teo,‡ Andrew Mente,‡ Matthew J. McQueen,‡,§ Johannes Zeidler,§ Paul Poirier,∥ Scott A. Lear,⊥ Andy Wielgosz,# and Philip Britz-McKibbin*,† †
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario L8S 4M1, Canada Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario L8L 2X2, Canada § Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario L8S 4K1,Canada ∥ Faculté de Pharmacie, Université Laval, Quebec City, Province of Quebec G1V 0A6, Canada ⊥ Faculty of Health Sciences, Simon Fraser University, Vancouver, British Columbia V5A 1S6, Canada # Department of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada ‡
S Supporting Information *
ABSTRACT: Iodine deficiency is the most common preventable cause of intellectual disabilities in children. Global health initiatives to ensure optimum nutrition thus require continuous monitoring of population-wide iodine intake as determined by urinary excretion of iodide. Current methods to analyze urinary iodide are limited by complicated sample pretreatment, costly infrastructure, and/or poor selectivity, posing restrictions to large-scale epidemiological studies. We describe a simple yet selective method to analyze iodide in volume-restricted human urine specimens stored in biorepositories by capillary electrophoresis (CE) with UV detection. Excellent selectivity is achieved when using an acidic background electrolyte in conjunction with dynamic complexation via α-cyclodextrin in an unmodified fused-silica capillary under reversed polarity. Sample self-stacking is developed as a novel online sample preconcentration method to boost sensitivity with submicromolar detection limits for iodide (S/N ≈ 3, 0.06 μM) directly in urine. This assay also allows for simultaneous analysis of environmental iodide uptake inhibitors, including thiocyanate and nitrate. Rigorous method validation confirmed good linearity (R2 = 0.9998), dynamic range (0.20 to 4.0 μM), accuracy (average recovery of 93% at three concentration levels) and precision for reliable iodide determination in pooled urine specimens over 29 days of analysis (RSD = 11%, n = 87).
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States are marginally iodine deficient.5 Therefore, continuous monitoring of iodine status is an essential part of universal salt iodization programs10,12,13 with dietary iodine intake recommended to be 150 μg/day for adults and 250 μg/day for pregnant women.3 The best single measurement to evaluate median iodine intake in the population is via excreted urinary iodide, which represents more than 90% of the iodine recently ingested.2,3,14,15 For this reason, iodide concentrations from random spot urine samples are often used in epidemiological studies for iodine status assessment. However, simple, selective, and cost-effective assays are needed to analyze submicromolar levels of urinary iodide for population health.16 A kinetic spectrophotometric assay based on the classic Sandell-Kolthoff reaction is the most widely used method for urinary iodide determination, where iodide serves as a catalyst
odine is an essential micronutrient needed for the biosynthesis of thyroid hormones, which are critical in the regulation of cellular metabolism, as well as in normal growth and mental development.1,2 In order to provide a consistent source of iodine to the population and prevent iodine deficiency disorders (IDDs), many countries have adopted table salt iodization as a public health policy. Although significant improvement has been achieved in the reduction of endemic goiter and cretinism, other IDDs remain problematic with almost 2 billion people worldwide at risk for iodine insufficiency3 that is associated with impaired cognitive development in children, as well as weight gain, depression, thyroid disorders, and cardiovascular diseases later in life.4−7 Several developed countries, in which iodine deficiency was believed to be eradicated some decades ago, are facing mild iodine deficiency due to reduced intake of iodine-rich foods, increased consumption of noniodized processed foods, and/or exposure to iodide uptake inhibitors in the environment.8−11 For instance, about one-third of pregnant women in the United © 2014 American Chemical Society
Received: August 28, 2014 Accepted: October 3, 2014 Published: October 3, 2014 10010
dx.doi.org/10.1021/ac503231u | Anal. Chem. 2014, 86, 10010−10015
Analytical Chemistry
Letter
Figure 1. Injection configuration and buffer conditions used for iodine status determination by CE with UV detection via sample self-stacking. Chloride in urine samples serves as a LE, while a BGE containing dihydrogen phosphate (pH 3) serves as TE. Dynamic complexation of iodide with α-CD is critical for method selectivity and sample self-stacking. This electrokinetic focusing mechanism allows for online sample preconcentration of iodide directly in human urine with submicromolar detection limits.
attain submicromolar detection limits for assessment of iodine nutritional insufficiency (
