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 (187Re and 130Te) 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.
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form.
Employment or Leadership: None declared.
Consultant or Advisory Role: None declared.
Stock Ownership: None declared. Honoraria: None declared.
Research Funding: P. Britz-McKibbin, Natural Sciences and Engineering Research Council of Canada; A. Nori de Macedo, Ontario Trillium Scholarship.
Expert Testimony: None declared.
Patents: P. Britz-McKibbin, patent number 15/281,205.
Role of Sponsor: No sponsor was declared.
- Received December 15, 2016.
- Accepted February 9, 2017.
- © 2017 American Association for Clinical Chemistry