j. Cosmet. Sci., 52, 399-405 (November/December 2001) Simultaneous quantitative determination of fluorine and sodium monofluorophosphate in oral hygiene products LAI-HAO WANG, Department of Applied Chemistry, Chia Nan University of Pharmacy and Science, Tainan, Taiwan 7171 O, R.O.C. Accepted for publication August 15, 2001. Synopsis An ion chromatographic method for simultaneous quantitative determination of fluorine and sodium monofluorophosphate in oral hygiene products is described. The liquid chromatographic system consisted of an IC A1 polymethacrylate-based anion exchanger and carbonate buffer (pH 9.85) as the mobile phase with a conductive detector. Various excipient ions were investigated with respect to their interference with the determination of fluoride. Comparison with results obtained from a fluoride-ion electrode technique show good agreement. INTRODUCTION Epidemiologic and experimental evidence concerned with the relationship of fluoride to dental caries suggests that fluoride solutions applied to the external surfaces of teeth may decrease their susceptibility to caries. The first two papers on the effect of topical application of fluorides were made by Bibby in 1942 (1) and Chenye in 1946 (2). Fluorine derivatives including sodium fluoride, stannous fluoride, and sodium mono- fluorophosphate (MFP, Na2PO3F) are incorporated into dentifrices or mouthwashes as chemotherapeutic agents (3). However, fluoride is absorbed into the blood from the gastrointestinal tract. It is then mostly deposited in bone or excreted in urine (4). The acute and chronic toxicity values (LD5o values in the rat and mouse) of sodium fluoride, stannous fluoride, and MFP have been investigated. The toxicity of stannous fluoride is similar to that of sodium fluoride. Stannous fluoride and sodium fluoride are more toxic than MFP by factors of 1.4-3.0 (4). The Food and Drug Administration (FDA) has promulgated regulations for safe and effective oral hygiene products. Active anticaries agents in dentifrices were 0.22%, 0.40% and 0.76% for sodium fluoride, stannous fluoride, and MFP, respectively. The final product, containing 0.02% fluoride ion in oral rinses, was based on in vitro data as well as on clinical trials (4). A mutagenicity study on three fluorine derivatives selected from the cosmetic guidelines 399

400 JOURNAL OF COSMETIC SCIENCE of the Council of the European Communities (27 July 1976) was published (5). Stannous fluoride was slightly mutagenic in the Ames test. Today, over 90% of the dentifrices sold in Taiwan contain fluoride from one of two major sources (sodium fluoride and MFP). There are reports that a mixture of sodium fluoride and MFP is superior in efficacy to MFP alone in a dentifrice base (4). Dentifrices with mixed fluoride systems been marked. Quantitative determination of fluoride and MFP are important for quality control and stability evaluation of these products. Gas chromatographic (6-8), fluoride-ion electrode (6,8,9) high-performance liquid chro- matographic (10), and ion chromatographic (11,12) techniques have been used to de- termine fluoride derivatives in toothpastes. Gas chromatographic methods involve the chromatographic analysis of trimethyl fluorosilane resulting from the reaction of tri- methyl chlorosilane with fluoride ions in the toothpaste. A fluoride-ion electrode tech- nique was used only for the determination of soluble fluoride derivatives. However, MFP is soluble in water to the extent of 42% saturation and is slowly hydrolyzed in the presence of hydrochloric acid. These methods are laborious and time-consuming. The use of high-performance liquid chromatography required a postcolumn detection system in order to analyze orthophosphate, diphosphate, triphosphate, and cyclotriphosphate in MFP samples (10). Ion chromatographic methods for direct determination of MFP in toothpaste have been reported (11,12). However, oral hygiene formulations commonly contain abrasives (phosphate), an antibacterial agent (cetylpyridium chloride), astringent salts (zinc chloride), and a surfactant (sodium lauryl sulfate). These excipient anion ions were found not to be ideal for resolving fluoride and phosphate at pH 5.3-5.7. This present paper describes the application of various pH to separate rapidly and efficiently the peaks of interest. The results were compared with those obtained with the fluoride- ion electrode method. EXPERIMENTAL ION CHROMATOGRAPHY The liquid chromatograph was the Shimadzu LC-10 AD chromatography module con- taining the pump and conductivity detector (Shimadzu CDD-6A). The analytical col- umn used a Shim-Pack IC-A1 (4.6 mm ID x 10 cm) polymethacrylate-based anion exchanger (10 l•m). Chromatographic data were collected and analyzed with a Chroma- topac C-R6A. The following chromatographic conditions were used: eluent flow rate, 1.5 ml min -•' conductivity temperature, 40øC sensitivity, 1.0 l•s cm -•' injection volume, 50 lal recorder chart speed, 5 mm/min -• All reagents used were analytical grade. The MFP was obtained from Aldich Chemical Corporation and had an assay value of 95%. The pH of the eluent, containing 0.94 m mol 1 -• sodium carbonate, was adjusted to 9.85 and 11.00 with 0.31 m mol 1 -• sodium hydrogen carbonate and 1.0 mol 1-1 sodium hydroxide, respectively. The standard fluoride (1000 mg 1-•), chloride (1000 mg l-i), sulfate (1000 mg 1-•), and MFP (0.1%) solutions were prepared by dissolving the appropriate amounts of sodium salt in double deionized water. A 500-mg amount of toothpastes or mouthwashes was accurately weighed into a beaker, and 20 ml of deionized water was added and stirred until the sample was fully dispersed.