Potassium chloride and potassium bicarbonate effervescent tablets are used to prevent low levels of potassium in blood [1]. Using the monographs from the United States Pharmacopeia and National Formulary (USP-NF) allows pharmaceutical manufacturers and labs to fulfill strict quality regulations for drugs and formulations.
The USP has embarked on a global initiative to modernize many existing monographs. The monograph «Potassium Bicarbonate and Potassium Chloride Effervescent Tablets for Oral Solution» comprises different methods to determine potassium, sodium, but also chloride in these tablets [2]. Ion chromatography (IC) with suppressed conductivity detection has been approved by the USP as a validated method to quantify chloride content in potassium bicarbonate and potassium chloride effervescent tablets for oral suspension [2]. The Metrosep A Supp 16 - 100/4.0 column provides the required separation of chloride. The method is validated according to USP General Chapter <621> Chromatography, system suitability [3].
Sample analyses are performed with a solution of the respective effervescent tablets. No additional sample preparation is required.
A sample stock solution (nominally 4434.52 μg/mL chloride) is prepared by adding 50 g (equivalent to 10 tablets weight) of finely powdered potassium bicarbonate and potassium chloride effervescent tablets for oral solution to a 2000 mL volumetric flask. The powder is dissolved in 200 mL ultrapure water (UPW). After effervescence ceases, the volumetric flask is filled up to the mark. A small volume (1.692 mL) of this stock solution is transferred to a 500 mL volumetric flask and filled up to the mark with UPW. This final sample solution nominally contains 15.0 μg/mL chloride.
The working standard solution of 15 μg/mL is prepared from a USP Potassium Chloride RS standard.
Samples and standard solutions are injected directly into the IC using an 858 Professional Sample Processor (Figure 1). Separation of chloride from other anions is performed using a Metrosep A Supp 16 - 100/4.0 column. This anion-exchange column, consisting of a strong ion exchanger made from monodisperse porous polystyrene/divinyl benzene beads combined with quaternary amines, qualifies for certain USP methods using the USP chromatographic column packing.
The calibration is performed with a 6-point linear calibration curve using a concentration range of 2.25–22.50 μg/mL chloride. The sample is then analyzed in duplicate.
Table 1. Requirements for the IC method for chloride determination as per USP Monograph «Potassium Bicarbonate and Potassium Chloride Effervescent Tablets for Oral Solution» [2].
| Column with L91 packing | Metrosep A Supp 16 - 100/4.0 |
|---|---|
| Eluent | 15 mmol/L sodium carbonate, 1.5 mmol/L sodium hydroxide |
| Flow rate | 0.8 mL/min |
| Temperature | 45 °C |
| Injection volume | 20 μL |
| Detection | Suppressed conductivity |
The IC assay for chloride content was validated according to the USP Monograph «Potassium Bicarbonate and Potassium Chloride Effervescent Tablets for Oral Solution» [2]. The accuracy of the chloride determination in the sample was calculated as 101.2% (Figure 2) and falls into the acceptance criteria. All analytical quality requirements were fulfilled, e.g., the correlation coefficient for chloride was 0.9998, and the relative standard deviation of repeated standard solutions was 0.05% (n = 6) (Table 2).
Table 2. Analytical quality criteria for method acceptance according to USP Monograph «Potassium Bicarbonate and Potassium Chloride Effervescent Tablets for Oral Solution» [2].
| Parameter | Actual | USP requirement | Status |
|---|---|---|---|
| % RSD | 0.05 | NMT 0.5 | Pass |
| Tailing factor | 1.27 | NMT 2.0 | Pass |
| Recovery | 101.2% | 90–110% | Pass |
| Resolution | 2.48 | NLT 1.5 | Pass |
The presented IC method for chloride in potassium bicarbonate and potassium chloride effervescent tablets for oral solution is officially included into the USP [2]. Chloride separation is performed with a strong anion-exchanger – the Metrosep A Supp 16 - 100/4.0 column, corresponding to packing material L91. 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 chloride according to the USP requirements. Further 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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