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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 determination in talc USP -determination of chrysotile as impurity Talc USP 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 2S4010 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 hydrated magnesium silicate may ideally be represented as 8Si4010 The structure of both minerals 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 tale containing some chlorite The concern is for rather gross impurities such as excesses of pH or soluble iron Thus a rather substantial contamination of the talc with chrysotile could occur and no cause for rejection would appear unless the product became gritty Several tests can be proposed to detect the chrysotile in talc but each suffers from some difficulty all relating to the large ratio of tale to chrysotile which should be present Obviously a simple determination of magnesium hoping to find the excess due to the chrysotile would fail because of the natural variability of the talc itself 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 examination 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 Bromcresol purple 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 solution 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 Chrysotilewas used as received except for reduction in parti- cle size to that of the talc being tested Procedure three 0.2000 - 0.0010 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 and also provide a ml sample of 50 ethanol to serve as a blank Give all samples and the blank an ultrasonic treatmentfor 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 ...m filter Dilute a 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 ray diffraction 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 The 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 resulted in a plugged filter before enough filtrate could be collected Figure 1 shows a typical determination on a talc spiked with 0.300 ABSORNCE 2 1 0 1 2 3 4 5 6 IN SAMPLE ADDED TO SAMPLE CHRYSOTILE mg Figure 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 Plainville N.Y. The microtip adapter was used * Millipore Systems Ultrasonics Inc. 268 / Journal of Pharmaceutical Sciences 0.5 chrysotile The result from the assay in Fig 1 indicates 1.1 mg chrysotile in a 200 sample or 0.55 All tests for precision of the assay were done on spiked samples A limited number of determinations 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 obtainedThis 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 5 Geology 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 1968 2 R. Merliss Science 173 1971 3 The United States Pharmacopeia 18th rev Mack Pub- lishing Co. Easton Pa 1970 p 708 4 A. L. Rickards Anal Chem 44 1972 ACKNOWLEDGMENTS AND ADDRESSES Received April 30 1973 from the Analytical Development partment Eli Lilly and Company Indianapolis IN 46206 Accepted for publication September 20 1973 The author thanks the Johns Manville Research Center Deand 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 determination is dependent upon the combined hydroxyl and primary amino moieties It is postulated that phenylpropanolamine hydrochloride 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 phenylalanine clearly demonstrates the similarity of the reaction mecha- nism to the classic ninhydrin mechanism Keyphrases Phenylpropanolamine hydrochloride formulationscolorimetric analysis ninhydrin reagent Colorimetry phenylpropanolamine hydrochloride in mixed formulations Ninhydrin reagent 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 sy- rups elixirs suspensions nasal jellies and nasal so- lutions Recently because of the increased use of phenyl- a propanolamine hydrochloride in complex mixtures it has become necessary to develop specific and rapid method for its determination The method described in this report is dependent upon a colorimetric reto concentrations and therefore does not re- sponse 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 earth,, separation followed by spectrophotometry GLC extraction and titration exchange chromatography followed by titration with hydrochloric acid and periodate oxidation to benzaldehyde EXPERIMENTAL Reagents Buffer pH Dissolve 21.008 g of citric acid USP in 200 ml of water Add 200 ml of 1.0 N sodium hydroxide solution and dilute to 500 ml with distilled water Adjust the pH with sodium hydroxide or hydrochloric acid if necessary Potassium Accurately weigh 0.1628 g of potassium cyanide transfer to a 250 volumetric flask and dilute to vol- ume with water 1 Celite The sample preparation given for layered tablets capsules and combi- nation tablets is typical of that required for most dosage forms Vol 63 No. 2 February 1974 / 269