Potassium bicarbonate and potassium chloride effervescent tablets for oral solution are used to prevent hypokalemia (low levels of potassium in blood) [1]. Pharmaceutical manufacturers and laboratories must use approved quality monitoring techniques for drugs and formulations as stipulated by U.S. Pharmacopoeia (USP) monographs.
As an alternative to flame photometry, ion chromatography with non-suppressed conductivity detection has been approved by the USP as a validated method to quantify potassium content in potassium bicarbonate and potassium chloride effervescent tablets for oral solution [2].
The Metrosep C 6 - 150/4.0 column provides the required separation of potassium and magnesium. All acceptance criteria from the USP monograph «Potassium Bicarbonate and Potassium Chloride Effervescent Tablets for Oral Solution» are fulfilled [2]. The present IC method has been validated according to USP General Chapter <621> Chromatography, system suitability [3].
Sample solutions are prepared from commercially available potassium bicarbonate and potassium chloride effervescent tablets for oral solution. Standard analyses are performed with a solution of USP Potassium Chloride RS. No additional sample preparation is required.
The sample stock solution is prepared through the addition of 25 g finely powdered potassium bicarbonate and potassium chloride effervescent tablets for oral solution to a 1000 mL volumetric flask. The powder is dissolved in 200 mL ultrapure water. After effervescence ceases, the volumetric flask is filled up to the mark. This stock solution contains nominally 4809.48 mg/L potassium. A 1.533 mL aliquot of this stock solution is transferred to a 500 mL volumetric flask and is filled up to the mark with ultrapure water. This final sample solution nominally contains 15.0 μg/mL potassium.
A working standard solution of 15 μg/mL potassium chloride is prepared from the respective USP reference standards.
All solutions (i.e., samples and standards) are injected directly into the ion chromatograph (Figure 1) using an 858 Professional Sample Processor. Potassium is separated from all other cations using the Metrosep C 6 - 150/4.0 column.
The calibration is performed by using a 6-point linear calibration curve in the concentration range of 3.75–22.5 μg/mL potassium. The sample is then analyzed in duplicate.
Table 1. Requirements for the IC method as per USP Monograph «Potassium Bicarbonate and Potassium Chloride Effervescent Tablets for Oral Solution» [2].
| Column with L76 packing | Metrosep C 6 - 150/4.0 |
|---|---|
| Eluent | 4 mmol/L nitric acid |
| Flow rate | 0.9 mL/min |
| Temperature | 30 °C |
| Injection volume | 20 μL |
| Detection | Direct conductivity |
The IC assay for potassium content was validated according to USP Monograph «Potassium Bicarbonate and Potassium Chloride Effervescent Tablets for Oral Solution» [2]. The accuracy of the potassium determination was calculated as 105% (Table 2 and Figure 2).
All acceptance criteria were fulfilled, e.g., the correlation coefficient for potassium was 0.9999, the resolution of adjacent peaks, and the relative standard deviation of the standard solutions was <0.15% (n = 6) (Table 2).
Table 2. Required acceptance criteria according to USP Monograph Potassium Bicarbonate and Potassium Chloride Effervescent Tablets for Oral Solution [2] (Abbreviations: K+, potassium; Mg2+, magnesium).
| Parameter | Actual | USP requirement | Status |
|---|---|---|---|
| % RSD | 0.15 | NMT 1.0 | Pass |
| Tailing factor | 1.37 | NMT 2.0 | Pass |
| Recovery | 104.8% | 90–110% | Pass |
| Resolution K+/Mg2+ | 4.17 | NLT 2.0 | Pass |
The presented IC method for the determination of potassium content in potassium bicarbonate and potassium chloride effervescent tablets for oral solution using the Metrosep C 6 column (packing material L76) for separation is officially included into the USP [2]. Robustness and reliability of the method was demonstrated following the guidelines of the USP General Chapter <621> [3]. The presented setup is suitable to quantify potassium according to the USP requirements. Additional USP methods are summarized in the flyer «Bring your USP methods up to date!» [4].
- Kardalas, E.; Paschou, S. A.; Anagnostis, P.; et al. Hypokalemia: A Clinical Update. Endocr Connect 2018, 7 (4), R135–R146. https://doi.org/10.1530/EC-18-0109.
- Potassium Bicarbonate and Potassium Chloride Effervescent Tablets for Oral Solution; Monograph; U.S. Pharmacopeia/National Formulary: Rockville, MD. https://doi.org/10.31003/USPNF_M67253_02_01.
- <621> Chromatography, General Chapter; U.S. Pharmacopeia/National Formulary: Rockville, MD. https://www.uspnf.com/notices-gc-621-nitr-20220826.
- Metrohm AG. Bring Your USP Methods up to Date!, 2023. 8.000.5436EN
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Internal reference: AW IC IN6-1887-052018