Potassium analysis with ion chromatography according to USP testing methods

Method validation according to the U.S. Pharmacopeia

n 2010 the United States Pharmacopeia (USP) began modernizing their monographs[1]. As a part of this effort, test methods for the quantification of potassium now include ion chromatography. Ion chromatography is a viable alternative method for the analysis of potassium. Compared to other potassium analysis methods, ion chromatography has the advantage of analyzing multiple cationic species concurrently.

Potassium is essential for nerve transmission, muscle contraction, fluid balance, regulating blood pressure, and more. Low potassium levels (hypokalemia) can cause cramps, constipation, or even heart failure. Mild or moderate hypokalemia can be treated with potassium tablets or intravenous potassium infusions[2].

It is important to determine both the potassium content and possible impurities in these products. Pharmaceutical manufacturers and labs must follow the guidelines in USP monographs for testing drug products and dietary supplements.

As part of its modernization effort[1], the USP has updated several monographs to include ion chromatography (IC) as an analysis method for potassium. The USP now suggests IC as an alternative to the traditional methods of atomic absorption spectroscopy (AAS) and flame photometry.

AAS and flame photometry are based on measuring the characteristic emission or absorption spectra of atoms in a flame. These methods require flammable gases and costly equipment. IC is able to separate and quantify ions in a solution based on their different affinities to a stationary phase. This enables IC to measure multiple analytes in a single run, increasing its efficiency and versatility.

With IC, manual steps for matrix removal are unnecessary, as high-capacity columns offer excellent separation even in samples with a heavy matrix load. For example, IC can simultaneously determine the potassium content and the possible impurities, such as sodium and ammonium, in a pharmaceutical product or a dietary supplement.

The updated USP monographs for potassium analysis use a separation column with L76 packaging, such as the Metrosep C 6 – 150/4.0. This column is optimized to separate cations with large differences in concentration.

To learn more about the use of ion chromatography in various USP test methods, visit our webpage «Drug monographs, assays, and impurity evaluations using Metrohm Ion Chromatography».

References

[1] Santos, L. M.; Davani, B.; Anthony, C. M.; Clark, J. E. USP Monograph Modernization Initiative. https://www.americanpharmaceuticalreview.com/Featured-Articles/173161-USP-Monograph-Modernization-Initiative/ (accessed 2024-05-01).

[2] Kardalas, E.; Paschou, S. A.; Anagnostis, P.; Muscogiuri, G.; Siasos, G.; Vryonidou, A. Hypokalemia: A Clinical Update. Endocrine Connections 2018, 7 (4), R135–R146. https://doi.org/10.1530/EC-18-0109.