Les produits de soins dentaires comme le dentifrice contiennent souvent du fluorure de sodium pour favoriser la reminéralisation de l'émail des dents et prévenir les caries dentaires. [1]. L'OMS recommande une teneur en fluor de 1000 à 1500 mg/L dans le dentifrice pour les adultes afin de prévenir les caries dentaires. [2]. Les fabricants utilisent la monographie "Sodium Fluoride" de l'United States Pharmacopeia and National Formulary (USP-NF) pour quantifier le fluorure de sodium et ses contaminants anioniques, le chlorure et l'acétate, dans les produits de soins dentaires. [3].
La méthode USP validée propose la chromatographie ionique (IC) avec détection de conductivité supprimée pour effectuer le dosage du fluorure ainsi que la détermination des impuretés en un seul chromatogramme [3]. La méthode IC démontrée utilise la méthode Metrosep A Supp 16 - 250/4.0 (L91) et d'un éluant hydroxyde, en respectant tous les paramètres indiqués dans la monographie USP "Sodium Fluoride" [3]. Elle permet une excellente séparation du fluorure, de l'acétate et du chlorure et répond à tous les critères d'acceptation de la monographie. La méthode IC a été validée conformément aux chapitres généraux de l'USP <621> Chromatographie [4] et <1225> Validation des procédures officinales [5].
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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