歯磨き粉などの歯科ケア製品には、歯のエナメル質の再石灰化を支援し、歯科カリエス（虫歯）を予防するためにナトリウムフッ化物が含まれています[1]。WHOは、成人の歯周病予防のために歯磨き粉中に1000〜1500 mg/Lのフッ化物を推奨しています[2]。製造業者は、米国薬局方および国家規準（USP-NF）のモノグラフ「ナトリウムフッ化物」を使用して、歯科ケア製品中のナトリウムフッ化物およびその陰イオン性不純物である塩化物とアセテートを定量化します[3]。
検証されたUSP法では、フッ化物アッセイおよび不純物定量を単一のクロマトグラムで行うために、抑制導電度検出を備えたイオンクロマトグラフィ（IC）を提案しています[3]。実証されたIC法は、Metrosep A Supp 16 - 250/4.0 カラムと水酸化物溶出剤を使用し、USPモノグラフ「ナトリウムフッ化物」で指定されたすべてのパラメーターに準拠しています[3]。これにより、フッ化物、アセテート、および塩化物が優れた分離が行われ、モノグラフのすべての受容基準が満たされます。IC法は、米国薬局方一般章<621>クロマトグラフィ[4]および<1225>薬局方手続きの検証[5]に従って検証されています。
The standard solutions and the system suitability solutions are prepared from the respective 1000 µg/mL certified standards by dilution with ultrapure water (UPW).
For the fluoride assay, the standard solution is obtained by diluting a sodium fluoride solution to 2 µg/mL. The system suitability solution contains 2 µg/mL sodium fluoride and 1 µg/mL sodium acetate. For the impurity test, the standard solution consists of 0.2 µg/mL sodium chloride in UPW. The system suitability solution for the impurity test contains 1 mg/mL sodium fluoride and 1 µg/mL sodium chloride in UPW.
Sample analyses are performed with a solution prepared from commercially available sodium fluoride salt. The sample solution is prepared by dissolving and diluting sodium fluoride salt with UPW to a nominal concentration of 2 µg/mL which corresponds to 0.9 µg/mL fluoride (for the assay). For the impurity test, samples were diluted to a nominal concentration of 1 µg/mL sodium fluoride.
No additional sample preparation is required.
Samples and standard solutions were directly injected into the IC using a 919 IC Autosampler plus (Figure 1).
Fluoride was separated from acetate and chloride using a potassium hydroxide eluent and the column Metrosep A Supp 16 with column material L91 (Table 1). The analytes were quantified by evaluating their conductivity signal after chemical suppression.
The calibration was performed using a single 2.0 µg/mL standard injected six times. The sample was analyzed in duplicate.
Table 1. Requirements for the IC method as per USP Monograph «Sodium Fluoride» [3].
| Column with L91 packing | Metrosep A Supp 16 - 250/4.0 |
|---|---|
| Eluent | 15 mmol/L potassium hydroxide |
| Flow rate | 1.0 mL/min |
| Temperature | 40 °C |
| Injection volume | 20 µL |
| Detection | Conductivity with suppression |
The IC assay for fluoride content was validated according to USP Monograph «Sodium Fluoride» [3]. Suitability requirements for resolution, tailing factor, and relative standard deviation were fulfilled (Table 2).
Table 2. Suitability requirements for the assay.
| Parameter (assay) | Actual | USP requirement | Status |
|---|---|---|---|
| Resolution F-/acetate | 5.9 | NLT 1.5 | Pass |
| Tailing factor | 1.1 | NMT 2.0 | Pass |
| RSD fluoride (%, n=5) | 0.52 | NMT 0.73 | Pass |
The chromatographic resolution between fluoride and acetate is shown in Figure 2. The recovery of fluoride for the sample analysis (99.7%) was within the USP acceptance criteria (98–102%).
Regarding the impurity tests for potential contamination with chloride, the IC method showed excellent compliance with the USP requirements (Table 3).
Table 3. Suitability requirements for the impurities in sodium fluoride.
| Parameter (impurity) | Actual | USP requirement | Status |
|---|---|---|---|
| Resolution F-/Cl- | 7.7 | NLT 4 | Pass |
| RSD fluoride (%, n=5) | 4.2 | NMT 5 | Pass |
| S/N ratio Cl- | >740 | NLT 20 | Pass |
Figure 3 shows the chromatographic resolution between fluoride and chloride.
In all tested samples, the chloride content was well below the acceptance criteria of 0.012% (Table 4).
Table 4. Results of the chromatograms shown in Figures 2 and 3.
| Anion | Sample ID | Result [%] | USP Limit [%] |
|---|---|---|---|
| 1 Fluoride | Assay | 99.7 | 98–102 |
| 2 Chloride | Impurity | 0.0016 | ≤0.012 |
The presented IC method is suitable to determine sodium fluoride and its impurities according to the USP Monograph «Sodium Fluoride». The method helps manufacturers of dental care products to determine fluoride content as well as impurities more easily in toothpaste.
- Yeung, C. A. A Systematic Review of the Efficacy and Safety of Fluoridation. Evid Based Dent 2008, 9 (2), 39–43. https://doi.org/10.1038/sj.ebd.6400578.
- WHO. A.14 Fluoride Toothpaste – Dental Caries; Expert Committee on Selection and Use of Essential Medicines Application review; WHO, 2021.
- Sodium Fluoride; Monograph; U.S. Pharmacopeia/National Formulary: Rockville, MD. https://doi.org/10.31003/USPNF_M76470_04_01.
- 〈621〉 Chromatography; General Chapter; U.S. Pharmacopeia/National Formulary: Rockville, MD. https://doi.org/10.31003/USPNF_M99380_01_01.
- 〈1225〉 Validation of Compendial Procedures; General Chapter; U.S. Pharmacopeia/National Formulary: Rockville, MD. https://doi.org/10.31003/USPNF_M99945_04_01.
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