Iodide Assay by Ion Chromatography

Significance of the Topic

The accurate and reliable quantification of iodide in potassium iodide (KI) is critical for ensuring the efficacy of KI as a thyroid blocker in radiation emergencies. Traditional manual titration methods suffer from poor precision and potential user variability, prompting a need for a modern, selective, and sensitive analytical approach that aligns with USP modernization efforts.

Study Objectives and Overview

This work aimed to develop and validate a single ion chromatography (IC) procedure capable of both identification and assay of iodide in KI according to USP <1225> guidelines. The method was designed to replace manual titration in the USP Potassium Iodide Monograph and to streamline quality control workflows for KI and related formulations.

Methodology and Instrumentation

The assay employs suppressed conductivity detection following separation of anions on a Metrosep A Supp 17 – 100/4.0 (L91 packing) column at 45 °C, with a 10 mM Na2CO3 eluent at 1.0 mL/min and 20 μL injection volume.

• Instrument: Metrohm 940 Professional IC Vario
• Column: Metrosep A Supp 17 – 100/4.0, L91 packing
• Detection: Conductivity after suppression (no CO₂ suppression)
• Eluent: 10 mM sodium carbonate
• Run time: 10 minutes

Main Results and Discussion

Validation parameters met stringent acceptance criteria:

• Specificity: No interference observed from diluent, resolution solution, or sample matrix; phosphate resolved from iodide with a resolution >6.5.
• Linearity: Demonstrated over 3.0–22.5 mg/L (20–150% of nominal) with R² = 0.9999 and an intercept bias of 0.73%.
• Precision: System suitability RSD ≤0.5% (standard) and assay repeatability RSD ≤1.0% (sample); intermediate precision RSD ≤1.0% across analysts.
• Accuracy: Average assay results within 100 ± 2% of labeled value; recovery between 99.0% and 101.0% of specification.
• Solution Stability: Peak area change ≤0.77% over the tested period.

Benefits and Practical Applications

The unified IC method provides selective, sensitive detection of iodide while simultaneously monitoring common anionic impurities (chloride, sulfate). It replaces manual titration, improving precision and reducing analysis time to 10 minutes. The procedure is applicable to KI salt and over-the-counter formulations such as oral solutions or tablets.

Future Trends and Applications

Advancements may include automation and high-throughput IC systems, integration with mass spectrometric detection for enhanced specificity, and expansion to complex matrices such as biological fluids. The method framework can be adapted for other pharmacopeial monographs targeting anionic species.

Conclusion

A single suppressed-conductivity IC method was successfully developed and validated for iodide assay and identification in KI. The approach simplifies QA/QC operations, meets USP requirements, and offers robust performance metrics suitable for routine laboratory use.

Reference

• Paul S, Narayanan H, Chang M, Gump E. Iodide Assay by Ion Chromatography. Metrohm USA Application Note 8.000.6109EN.
• United States Pharmacopeia. USP Monograph: Potassium Iodide.