Background: A capillary electrophoresis (CE) assay was recently introduced as a new method for monitoring iodine nutrition in large-scale epidemiological studies. However, further tests revealed unanticipated matrix-dependent interferences when analyzing submicromolar levels of iodide in human urine as the predominate ionic form of dietary iodine. Herein, we describe a rigorous validation study that was used to identify sources of bias and establish modifications to the original CE method to improve method accuracy. Methods: An interlaboratory method comparison using CE with UV detection and inductively coupled plasma-mass spectrometry (ICP-MS) was performed to quantify urinary iodide concentrations (n = 71) independently at McMaster University and Hamilton General Hospital, as well as the CDC as part of their quality assurance program. A positive bias in the original CE method was indicated, and buffer conditions were subsequently optimized to overcome matrix interferences for reliable iodine status determination. Results: Positive bias in CE was attributed to variable concentrations of sulfate, a major urinary anion interference with similar mobility to iodide under the conditions originally reported. By increasing the concentration of α-cyclodextrin in the background electrolyte, the CE method was able to tolerate urinary sulfate over its normal physiological range without loss in signal response for iodide. The optimized CE assay generated results that were consistent with ICP-MS using 2 different internal standards (187 Re and 130 Te) with a median bias under 10%. Conclusions: CE offers a simple, selective, and cost-effective separation platform for surveillance of the iodine status of a population requiring only small volumes (<10 μL) of biobanked urine specimens, which is comparable to previously validated screening methods currently used in global health initiatives for prevention of iodine deficiency disorders. IMPACT STATEMENT A capillary electrophoresis (CE) method presented here offers a simple, selective, and cost-effective microseparation platform for urinary iodide determination, which is essential to support global health initiatives for prevention of iodine deficiency disorders. An interlaboratory method comparison was performed to identify and address sources of bias, resulting in an optimized CE method that generated consistent results in comparison to the reference method, inductively coupled plasma-mass spectrometry (ICP-MS). The validated CE assay allows for continuous monitoring of iodine nutrition in populations that is applicable to volume-restricted urine samples without complicated sample workup, expensive infrastructure, or high operating costs.

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