カリウム塩化物と炭酸水素カリウムの泡立つ錠剤は、血液中のカリウムの低レベルを予防するために使用されます[1]。米国薬局方および国家規準（USP-NF）のモノグラフを使用することで、製薬メーカーや研究所は、薬品や製剤の厳格な品質規制を遵守することができます。

米国薬局方は、多くの既存のモノグラフを近代化するためのグローバルイニシアチブに着手しました。モノグラフ「口腔用溶液用カリウム炭酸水素カリウムおよびカリウム塩化物泡立つ錠剤」には、これらの錠剤中のカリウム、ナトリウム、塩化物を決定するための異なる方法が含まれています[2]。抑制導電度検出を備えたイオンクロマトグラフィ（IC）は、口腔用懸濁剤としてのカリウム炭酸水素カリウムとカリウム塩化物泡立つ錠剤中の塩化物含量を定量化するための検証された方法として、米国薬局方によって承認されています[2]。Metrosep A Supp 16 - 100/4.0 カラムは、塩化物の必要な分離を提供します。この方法は、米国薬局方一般章<621>クロマトグラフィ、システム適合性[3]に従って検証されています。

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.

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).

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].