Category: Formulation and Quality
Purpose: Potassium iodide (KI) is used to treat overactive thyroid and to protect the thyroid gland from the effects of radiation from inhaled or swallowed radioactive iodine. The effectiveness of KI as a specific blocker of thyroid radioiodine uptake is well established. When administered in the recommended dose, KI is effective in reducing the risk of thyroid cancer in individuals or populations at risk for inhalation or ingestion of radioiodines. Currently in the USP Potassium Iodide monograph, iodide identification is done by wet chemistry method and assay by manual titration method. Manual titration has history of poor precision and accuracy. As a part of USP’s global monograph modernization initiative, an alternative selective and sensitive Ion chromatography (IC) method is developed and validated. The proposed IC method could also be used for identification test, as an alternative to the wet chemistry method.
Methods: Current assay of KI is based on manual titration against Potassium Iodate under acidic condition, using Amaranth indicator until the red color just changes to yellow. This titration using visual indication method is hard to follow and gives poor precision and accurate results. Ion Chromatography on the other hand is best suitable for separation of mono, divalent anions and organic acids simultaneously in presence of complex sample matrices. A Metrosep A Supp 17 100/4.0 mm column with L91 packing was identified as the most suitable for the separation of iodide based on column chemistry. Two different methods based on UV detection and Conductivity detection after suppression was tested for the Iodide assay. Suppressed conductivity detection was found to be precise and accurate and allowed the simultaneous detection of other impurities like chloride and sulfate. Suppressed conductivity detection-based IC method was fully validated as per USP validation of compendial methods
Results: Method validation elements of specificity, linearity, system suitability, solution stability, accuracy and precision, and intermediate precision were investigated for Potassium Iodide assay. Validation results met the acceptance criteria and are summarized in Table1. Validation data demonstrated that the Assay procedure can be used for the ID of Iodide in Potassium Iodide. Specificity was checked with diluent, resolution solution, standard solution, and sample solution to ensure no interference or co-elution with the Iodide peak (Figure. 1). The linearity of Iodide was investigated over the concentration range from 3.0 mg/L to 22. 5 mg/L of Iodide covering 20% to 150% of the expected Iodide concentration. The correlation coefficient was found to be 0. 9999 and the calculated Y-intercept bias was 0. 73% of the 100% linearity level response (figure. 2).
Conclusion: Single IC procedure for Iodide assay and identification in Potassium Iodide salt was developed and validated. Single chromatographic method for assay and identification simplifies the overall QA/QC workflow. A Metrosep A Supp 17 100/4.0 mm column with L91 packing with optimized chromatographic condition is suitable for fast and reliable identification and quantification of Iodide in potassium iodide salt and can be utilized for iodide assay in other OTC formulations such as potassium iodide oral solution and potassium iodide tablets.
Hari Narayanan– Metrohm USA, Riverview, Florida
Edwin Gump– Rockville, Maryland
Michael Chang– scientific liaison officer, United States Pharmacopeia (USP), Rockville, Maryland
Karen Poe– Event Manager, Metrohm USA, Riverview, FL