689459

Fluoride in OTC Products by Ion Chromatography
Shibu Paul1, Hari Narayanan1, Michael Chang2, Ed Gump2

CONTACT INFORMATION: shibu.paul@metrohmusa.com

PURPOSE
Fluoride is commonly used in dental products to help
prevent tooth decay. Fluoride products are intended toprevent the formation of cavities and when present in highconcentrations are regulated by 21 CFR 355. Three fluoride
compounds used in Over‐the‐Counter (OTC) anti‐caries
dental products are sodium fluoride, stannous fluoride andsodium monofluorophosphate (MFP). The assay of fluoridein these active ingredients and finished formulations aredetermined by manual titration, or by ion‐selectiveelectrodes. As a part of USP’s global monographmodernization initiative, an alternative selective andsensitive method has been developed and validated – ion
chromatography (IC). The proposed IC method can also beused for the identification test as an alternative to the wet
chemistry method. Fluoride‐based monographs that arecurrently being modernized using ion chromatographic
methods are shown in Figure 1.

INSTRUMENTRESULTSA Metrosep A Supp 16 250/4.0 mm column with L91packing was used for fluoride assay procedures for USP
monograph modernization of sodium fluoride API,impurities in sodium fluoride, sodium fluoride tablet,
sodium fluoride gel, and sodium monofluorophosphate.
The results of the column equivalency study for thesodium fluoride oral solution are summarized in Table 1.
The separation of fluoride is well resolved from chloride in
the resolution solution (Figure 2), and from organic
impurities in two OTC drug products from Listerine(Figure3) and Colgate oral solution (Figure4).

Sodium Fluoride Oral Solution as per USP ‐ Summary Table

ParametersMetrohm

USP Monograph

Eluent

150 mg/L of anhydrous sodium carbonate and 1.0 mL/Lof 1 N sodium hydroxide in water.

150 mg/L of anhydrous sodium carbonate
and 1.0 mL/L of 1 N sodium hydroxide inwater.

System SuitabilitySolution

1.0 ug/mL of USP sodium fluoride RS and 0.5 ug/mL ofUSP sodium chloride RS in water

1.0 ug/mL of USP sodium fluoride RS and0.5 ug/mL of USP sodium chloride RS inwater

Sample Solution

Nominally 1.1 ug/mL of sodium fluoride from a portion of Nominally 1.1 ug/mL of sodium fluoride
oral solution in waterfrom a portion of oral solution in water

Detection

Conductivity with suppression (MSM+MCS)

Conductivity with suppression

ColumnMetrosep A Supp 1 –250/4.6 (SN 12008533)
Metrosep A Supp 1 –Guard/4.6 (SN 06207007)

L46
Column 4.0 mm x 250 mm; 10 um packing
Guard 4.0 mm x 50 mm; 10 um packing

Flow Rate

1.0mL/Min

1.0mL/Min

Injection Volume20µL

20µL

Run Time

NLT 2x fluoride peak
Fluoride (4.6)
Run time : 10 min

NLT 2x fluoride peak

Column Temperature

Room temperatureStatus••••••

Metrohm 940 Professional IC Vario
Detection: Conductivity Detection after Sequential Suppression
Column Temperature: 30° C
Flow Rate: 1.0 mL/min
Injection Volume: 20 μL
Eluent : 150 mg/L of anhydrous sodium carbonate and 1.0 mL/L of
1 N sodium hydroxide in water.
• Column: Metrosep A Supp 1‐250/4.6, packing L46

Not mentioned

System Suitability (n=6)
Resolution

11.4

NLT 1.5 between fluoride and chloride peak

Tailing Factor

1.2

NMT 2.0 for fluoride peak

1.3%

NMT 2.0% for fluoride ion

Relative Standard
Deviation

Fig 5. Ion Chromatography Instrument used for Fluoride Assay in OTC Products

Listerine Cuidado Total (Lot#2967B02)
Mean Sample
Recovery: Duplicate

METHOD
An ion‐selective electrode (ISE) has a specific shelf‐life andrequires periodic calibration to guarantee accurate results.
Electrode fouling and response change over time are
additional limitations of ISE. Ion chromatography, on theother hand, is well‐suited for the separation of mono anddivalent anions, and organic acids in the presence ofcomplex sample matrices such as OTC dental products. AMetrosep A Supp 16 250/4.0 mm column with L91 packing
was identified as the most suitable for the separation ofmonoatomic anions such as fluoride. The method forfluoride assay in sodium fluoride gel was developed andvalidated using 15mM potassium hydroxide as the mobilephase. A modified mobile phase containing a combinationof sodium carbonate and sodium hydroxide was used andMetrosep A Supp1 with L46 packing was used for anequivalent column study in a sodium fluoride oral solution.

98.7

90.0%‐110.0%

Sample Preparations

Colgate Plax Ice Infinity (Lot#8294BR122AH15:13)
Mean Sample
Recovery: Duplicate98.8

90.0%‐110.0%

Sample Preparations

Figure 1: Fluoride Monographs currently being
modernized using Ion Chromatography

Table I: Sodium Fluoride Oral Solution column equivalency dataDATA

CONCLUSION
A single IC procedure for fluoride assay and identification in
sodium fluoride oral solutions was developed and tested forcolumn equivalency. A Metrosep A Supp 16 250/4.0 mmcolumn with L91 packing is suitable for the separation offluoride from the rest of the impurities in sodium fluoride andother oral formulations. Divalent cations such as calcium,added as EDTA salt does not affect the suppressor. Chemical
regeneration ensures that the divalent cations are completely
removed and offers highly reproducible method performance.
A single chromatographic method for assay and identification
simplifies the overall QA/QC workflow. The addition ofMetrohm inline ultrafiltration helps protect the analyticalcolumn and enhances column life and performance.
Metrohm USA, Inc.1, United States Pharmacopeia2

Figure 2: System suitability solution for
Sodium Fluoride Oral Solution

Figure 3: Sample ‐ Fluoride in Listerine
Cuidado Total

Figure 4: Sample ‐ Fluoride in ColgatePlax Ice Infinity

Colgate and Listerine were not involved in this study.

8.000.6110EN