Document XRjmLMmr88DE7jQVR5dGz7Lng

FILE NAME: Talc (TALC) DATE: 1973 DOC#: TALC208 DOCUMENT DESCRIPTION: Journal Article - Detection and Determination of Chrysotile in Talc USP Detection and Determination of Chrysotile in Talc USP HARRY A. ROSE NOTICE THIS MATERIAL IS SUBJECT TO THE UNITED STATES COPYRIGHT LAW (TITLE 17, U.S. CODE FURTHER REPRODUCTION IN VIOLATION OF THAT LAW IS PROHIBITED. Abstract A procedure for the determination of chrysotile in talc was developed. It depends on the adsorption of a sulfonphthalein dye by chrysotile but not by talc. The final measurement is a spectrophotometric determination of the dye left in solution after the adsorption step. Keyphrases Chrysotile--determination in talc USP Talc USP --determination of chrysotile as impurity The wide use of talc as a dusting powder and as a diluent in capsule contents has caused concern about possible impurities, especially asbestos, in the talc. Cralley et al. (1) found asbestos in some cosmetic talcs, and asbestos in talc was implicated as a cause of stomach cancer in Japan (2). Talc, a hydrated magnesium silicate, may ideally be represented as Mg3(OH)2Si40io. It may be contaminated with other minerals such as quartz, dolomite, chlorite, and the various forms of asbestos. Of the asbestos minerals, chrysotile is currently of most physiological concern. Chrysotile, also a hy drated magnesium silicate, may ideally be represent ed as Mg6(OH)8Si40io. The structure of both miner als is apparently made up of sheets of silicon and oxygen atoms interspersed with sheets of magnesium and oxygen atoms, the difference being in the added magnesium and oxygen in the chrysotile structure. USP XVIII (3) is rather vague about the chemistry of talc and apparently would admit a talc containing some chlorite. The concern is for rather gross impuri ties such as excesses of pH or water-soluble iron. Thus, a rather substantial contamination of the talc with chrysotile could occur, and no cause for rejec tion would appear unless the product became gritty. Several tests can be proposed to detect the chryso tile in talc, but each suffers from some difficulty, all relating to the large ratio of talc to chrysotile which should be present. Obviously, a simple determina tion of magnesium, hoping to find the excess due to the chrysotile, would fail because of the natural vari ability of the talc itself. X-ray diffraction, which was used (4) very elegantly for measuring air pollution by chrysotile, becomes uncertain at low percentages when much talc is present. Optical microscopic ex amination suffers because the particles approach the limit of resolution of the instrument. The test described here detects chrysotile contam ination in talc but not the amphibole types of asbes tos such as tremolite. The test depends on the ad sorption of bromcresol purple by chrysotile and the lack of adsorption of that dye by talc. Although other sulfonphthalein dyes of this series have similar behavior, bromcresol purple was selected because of its convenient range for change of color to the acid form. EXPERIMENTAL Reagents--Bromcresol purple1 was used as received. A stock solution of this dye was made by dissolving 0.15 g in 250 ml of 95% ethanol and diluting to 500 ml with water. The working solu tion was made by taking 20 ml of the stock solution plus 40 ml of 95% ethanol and diluting to 100 ml with pH 4.2 acetate buffer. This working solution, when 10 ml is diluted to 25 ml with pH 4.2 acetate buffer, should have an absorbance of 0.325 at 422 nm. Chrysotile2 was used as received except for reduction in parti cle size to that of the talc being tested. Procedure--Weigh three 0.2000 0.0010-g samples of talc USP. To Sample 2, add about 3 mg of chrysotile, and to Sample 3, add about 6 mg of chrysotile, both accurately weighed. To each sample, add 10 ml of 50% ethanol-water, and also provide a 10-ml sample of 50% ethanol-water to serve as a blank. Give all samples and the blank an ultrasonic treatment3 for 2 min at 70 w of power. After the samples cool to room temperature, add 10 ml of working dye solution to each and to the blank. Mix and allow to stand for 30 min with occasional shaking. Then centrifuge the samples and blank, and filter through a 45-gm filter4. Dilute a 10-ml aliquot of each filtrate to 25 ml with pH 4.2 acetate buffer. Then determine the optical absorbance at 422 nm in a suitable spectrophotometer, and plot the absorbance against milligrams of chrysotile added (Fig. 1). By extrapolation to a baseline, the level of which is indicated by the blank, the chrysotile content of the talc may be determined. RESULTS AND DISCUSSION The assay design used here follows that used for an X-ray dif fraction determination of chrysotile in air pollution studies (4). The present design differs in that instead of a positive slope for additions of chrysotile (increased peak height), a negative slope is obtained (increased adsorption and, hence, lower amount of dye remaining). The advantage of using this design is that, in effect, an internal standard is being used which can compensate for variations in the dye used, and it makes a fixed calibration curve unnecessary. Tbe double-separation step involving centrifugation and filtra tion was needed because the finest talc and chrysotile particles could not be removed in a reasonable time by centrifugation alone. On the other hand, attempted direct filtration rapidly re sulted in a plugged filter before enough filtrate could be collected. Figure 1 shows a typical determination on a talc spiked with IN SAM PLE ADDED TO SAMPLE CHRYSOTILE, mg F ig u re 1-- Extrapolated graph of additions of chrysotile plotted against absorbance. 1 Matheson, Coleman and Bell. 2 Johns Manville Research Center. 3 Sonifier cell disrupter, model W185D, Heat Systems Ultrasonics, Inc., Plainville, N.Y. The microtip adapter was used. 4 Millipore. 268 / Journal of Pharmaceutical Sciences 0.5% chrysotile. The result from the assay in Fig. 1 indicates 1.1 mg chrysotile in a 200-mg sample, or 0.55%. All tests for precision of the assay were done on spiked samples. A limited number of de terminations on a sample containing 0.5% chrysotile indicated a standard deviation of 0.06%. To eliminate the possibility that a peculiarity of the chrysotile sample used was responsible for the dye adsorption, another sam ple was obtained5. This sample gave substantially the same ad sorption behavior as the first chrysotile sample. SUMMARY A determination of chrysotile impurity in talc USP was devel oped. The assay is useful at least at the level of 0.5% chrysotile. An internal standard method is used which eliminates the need 5Geology Department, Indiana University. for a standard calibration curve. The assay depends on the ad sorptive property of the chrysotile for a sulfonphthalein dye. REFERENCES (1) L. J. Cralley, M. M. Key, D. H. Groth, W. S. Lainhart, and R. M. Ligo, Amer. Ind. Hyg. Ass. J., 29, 350(1968). (2) R. R. Merliss, Science, 173,1141(1971). (3) "The United States Pharmacopeia," 18th rev., Mack Pub lishing Co., Easton, Pa., 1970, p. 708. (4) A. L. Rickards, Anal. Chem., 44, 1872(1972). ACKNOWLEDGMENTS AND ADDRESSES Received April 30, 1973, from the Analytical Development De partment, Eli Lilly and Company, Indianapolis, IN 46206 Accepted for publication September 20, 1973. The author thanks the Johns Manville Research Center and Dr. John M. Hayes of Indiana University for providing the chry sotile samples. Selective Determination of Phenylpropanolamine Hydrochloride in Pharmaceutical Dosage Forms by Reaction with Ninhydrin D. BURKE, V. S. VENTURELLA*, and B. Z. SENKOWSKI Abstract A colorimetric method for the determination of phenylpropanolamine, hydrochloride, based on the reaction with ninhydrin, was applied to various forms of pharmaceutical prod ucts. The method is applicable to pharmaceutical products that do not contain other primary or secondary amines. The determi nation is dependent upon the combined hydroxyl and primary amino moieties. It is postulated that phenylpropanolamine hy drochloride reacts with ninhydrin under the experimental condi tions by a mechanism similar to that for amino acids. A compari son of the molar absorptivities of phenylpropanolamine hydro chloride with those of amino acids, such as glycine and phenylal anine, clearly demonstrates the similarity of the reaction mecha nism to the classic ninhydrin mechanism. Keyphrases Phenylpropanolamine hydrochloride formulations-- colorimetric analysis, ninhydrin reagent Colorimetry--analysis, phenylpropanolamine hydrochloride in mixed formulations O Ninhydrin reagent--used to determine phenylpropanolamine hydrochloride in mixed formulations In the past few years, phenylpropanolamine hydro chloride has been used widely in many different pharmaceutical preparations as an adrenergic agent. This popularity can be attributed to the fact that it produces vascular and bronchial effects with little, if any, central effects. It is used in asthma and as a nasal decongestant, both locally and orally (1). Phenylpropanolamine hydrochloride can be found in many formulations including tablets, capsules, syl^ps, elixirs, suspensions, nasal jellies, and nasal sohitions. Recently, because of the increased use of phenyl propanolamine hydrochloride in complex mixtures, it has become necessary to develop a specific and rapid method for its determination. The method described in this report is dependent upon a colorimetric re sponse to concentrations and, therefore, does not re quire prior separation from other active ingredients present in many allergenic and cold preparations. By contrast, many reported methods require long and tedious separations prior to quantitative determina tion. A review of the literature (2-14) showed that a great variety of methods had been used to determine the phenylpropanolamine hydrochloride content in pharmaceutical formulations quantitatively. The methods used were diatomaceous earth1 separation followed by spectrophotometry, GLC, extraction and titration, anion-exchange chromatography followed by titration with hydrochloric acid, and periodate oxidation to benzaldehyde. EXPERIMENTAL2 Reagents--Citrate Buffer, pH 5.0--Dissolve 21.008 g of citric acid USP in 200 ml of water. Add 200 ml of 1.0 N sodium hydrox ide solution and dilute to 500 ml with distilled water. Adjust the pH with sodium hydroxide or hydrochloric acid, if necessary. Potassium Cyanide--Accurately weigh 0.1628 g of potassium cyanide, transfer to a 250-ml volumetric flask, and dilute to vol ume with water. 1 Celite. 2The sample preparation given for layered tablets, capsules, and combi nation tablets is typical of that required for most dosage forms. Voi. 63, No. 2, February 1974 / 269