689459

Iodide Assay by Ion Chromatography
Shibu Paul1, Hari Narayanan1, Michael Chang2, Ed Gump2

CONTACT INFORMATION: shibu.paul@metrohmusa.com

PURPOSE
Potassium iodide (KI) is used to treat overactive thyroid
and to protect the thyroid gland from the effects ofradiation from inhaled or swallowed radioactive iodine.
The effectiveness of KI as a specific blocker of thyroid
radioiodine uptake is well‐established. When administeredin the recommended dose, KI is effective in reducing therisk of thyroid cancer in individuals or populations at riskfor inhalation or ingestion of radioiodines. Currently, in theUSP Potassium Iodide Monograph, iodide identification isperformed by wet chemistry and assay by manualtitration. Manual titration has a history of reduced
precision and accuracy. As part of USP’s global monographmodernization initiative, an alternative selective andsensitive method was developed and validated – ionchromatography (IC). The proposed IC method can also beused for the identification test as an alternative to wetchemistry.

METHODThe current assay of KI is based on manual titration against
potassium iodate under acidic condition using an Amaranthindicator until the red color changes to yellow. This method using
a visual indication is difficult to follow, has poor precision andinaccurate results. Ion chromatography, on the other hand, iswell‐suited for the separation of mono and divalent anions, andorganic acids in the presence of complex sample matrices. A
Metrosep A Supp 17 100/4.0 mm column with L91 packing wasidentified as the most suitable for the separation of iodide. Two
different methods based on UV detection and conductivity
detection after suppression were tested for the iodide assay.
Suppressed conductivity detection was found to be precise andaccurate and allowed the simultaneous detection of otherimpurities such as chloride and sulfate. The suppressed
conductivity detection‐based IC method was fully validated as
per USP <1225> validation of compendial methods.

INSTRUMENTRESULTS
Method validation elements like specificity, linearity,system suitability, solution stability, accuracy and precision,and intermediate precision were investigated for thepotassium iodide assay. The validation results met theacceptance criteria and are summarized in Table 1. The
data demonstrated that the assay procedure can be used
for the identification of iodide in potassium iodide.
Specificity was checked with diluent, resolution solution,
standard solution, and sample solution to ensure nointerference or co‐elution with the iodide peak (Figure 1).
The linearity of iodide was investigated over theconcentration range from 3.0 mg/L to 22. 5 mg/L of iodide
covering 20% to 150% of the expected iodideconcentration. 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). The
potassium iodide sample assay chromatogram is shown inFigure 3. The instrumentation used and thechromatographic conditions are summarized in Figure 4.

DATA

Iodine Assay in Potassium Iodine Using Suppressed Conductivity
Metrosep A Supp 17 – 100/4.0, p/n 6.01032.410, S/N 0044.1002

Parameters

USP Requirement

Metrohm Procedure

Columns (L91)

NA

A Supp 17 100/4.0 (L91)/Supp 17
Guard/4.0 (L91)

EluentNA

10 mM Na2CO2

Flow RateNA

1.0 mL/Min

Detection

NASuppressed Conductivity/No CO2Suppression

Injection VolumeNA20 µL

Run Time

NA10 minutes

Column Temperature

NA45℃

Working Standard
Concentration

NA15 mg/L Iodine

SampleConcentrationNA

15 mg/L Iodine
SpecificityBlank

No interference with iodine peak

No interference with iodine

TailingIodine tailing is NMT 2.0 for standard

1.75

Interference/Co‐elution

Resolution of the nearest peak from iodine is NLT 2.0 for
6.5 between phosphate and iodine
resolution standard

Critical Pair

Resolution between iodine and adjacent impurity peakshould be NLT 1.5Status• Detection: Conductivity Detection after Suppression• Column Temperature: 45° C• Flow Rate: 1.0 mL/min• Injection Volume: 20 μL• Eluent : 10mM Na2CO3• Column: Metrosep A Supp 17‐100/4.0,
packing L91

NoneSuitability
15.0 mg/L IodineStandardSix replicate injections RSD in NMT 1.0%

0.41%

Solution Stability
15.0 mg/L IodineStandard & Sample

The change in peak is NMT 1.0% from the initial time
point (µS/cm*min)

Maximum 0.58 for standard and0.77 for sample

Linearity
Linearity solutions
ranging from 20%‐150%
(3/5/10/15/22.5
mg/L)

Correlation coefficient is NLT 0.999

0.99999

Y‐intercept

0.003808

Y‐intercept bias: ± 2.0% of 100% linearity level response 0.73%

Fig 4. Ion Chromatography Instrument Used for Iodide Assay

Repeatability and Accuracy
Accuracy/Precisionsample solution intriplicate at 80, 100 &120% levels (12, 15 &18 mg/L) analyzed
against standard

The average assay result should be (1) 100 ± 2% of themanufacturer’s CoA value or (2) 99.0% and NMT 101%of the monograph specification

Average assay result was 100%

The RSD of the nine assay results should be NMT 1.0%

RSD of nine assay results was 0.86%

Analyst 2Metrosep A Supp 17 – 100/4.0, p/n 6.01032.410, S/N 0082.1017

Intermediate Precision

Figure 1: Resolution Solution ‐Mixed Standard Anion• Metrohm 940 Professional IC Vario

KF Assay Validation Data Summary
Analyst 1Specificity

Figure 3: Sample ‐ Sigma
Aldrich, Potassium Iodide≥99% Assay, Part# 221944,
Lot# MKBX 6865VBlank

No interference with iodine peak

No interference with iodine

Tailing

Iodine tailing is NMT 2.0 for standard

1.6

Interference/Co‐elution

Resolution of the nearest peak from iodine is NLT 2.0 for
6.87 between phosphate and iodine
resolution standard

15.0 mg/L IodineStandard

Six replicate injections RSD is NMT 0.5%

Suitability
0.16%

Repeatability and Accuracy
Accuracy/Precisionsample solution intriplicate at 80, 100 &120% levels (12, 15 &18 mg/L) analyzed
against standard

The average assay result should be (1) 100 ± 2% of themanufacturer’s CoA value or (2) 99.0% and NMT 101%of the monograph specification

Average assay result was 100.1%

The RSD of the nine assay results should be NMT 1.0%

RSD of nine assay result was 0.84%

CONCLUSION
A single IC procedure for iodide assay and identification inpotassium iodide salt was developed and validated. A single
chromatographic method for assay and identification simplifies
the overall QA/QC workflow. A Metrosep A Supp 17 100/4.0mm column with L91 packing with optimized chromatographic
condition is suitable for fast and reliable identification andquantification of iodide in potassium iodide salt and can beutilized for iodide assay in other OTC formulations such as
potassium iodide oral solution and potassium iodide tablets.

Sample Assay Test

Figure 2: Linearity Iodide from
20% to 150% ( 3.0 µg/mL –22.5 µg/mL)

Analyze sample
solutions in duplicate
using the drug
products against
standard

The average assay result should be NLT 99.0% and NMT
100.5% of the monograph specifications

Sigma assay result was 98.9%/CoA
99.5%
Lab Chem assay result was
100.6%/CoA 99.8%

Table 1: Validation summary

Metrohm USA, Inc.1, United States Pharmacopeia2

8.000.6109EN