Calcium dobesilate monohydrateEUROPEAN PHARMACOPOEIA 8.0 Barium. To 10 mL of solution S add 1 mL of calcium sulfate Heavy metals (2.4.8) : maximum 20 ppm. 12 mL of solution S complies with test A. Prepare the reference solution R. After at least 15 min, any opalescence in the solution is not more intense than that in a mixture of 1 mL of solution using lead standard solution (2 ppm Pb) R. distilled water R and 10 mL of solution S. ASSAY Iron (2.4.9) : maximum 7 ppm, determined on solution S. Dissolve 0.280 g in 100 mL of water R and carry out the Magnesium and alkali metals : maximum 0.3 per cent. complexometric titration of calcium (2.5.11). To a mixture of 20 mL of solution S and 80 mL of water R add 1 mL of 0.1 M sodium edetate is equivalent to 14.70 mg 2 g of ammonium chloride R and 2 mL of dilute ammonia R1, of CaCl2,2H2O. heat to boiling and pour into the boiling solution a hot solution of 5 g of ammonium oxalate R in 75 mL of water R. LABELLING The label states, where applicable, that the substance is suitable Allow to stand for 4 h, dilute to 200 mL with water R and filter through a suitable filter. To 100 mL of the filtrate add 0.5 mL for use in the manufacture of dialysis solutions. of sulfuric acid R. Evaporate to dryness on a water-bath and ignite to constant mass at 600 ± 50 °C. The residue weighs a STORAGE maximum of 5 mg. In an airtight container. Heavy metals (2.4.8): maximum 15 ppm. 01/2008:0707 12 mL of solution S complies with test A. Prepare the reference corrected 6.0 solution using lead standard solution (2 ppm Pb) R. CALCIUM CHLORIDE HEXAHYDRATE Calcii chloridum CaCl2,6H2O [7774-34-7] ASSAY Dissolve 0.200 g in 100 mL of water R. Carry out the complexometric titration of calcium (2.5.11). hexahydricum 1 mL of 0.1 M sodium edetate is equivalent to 21.91 mg Mr 219.1 of CaCl2,6H2O. DEFINITION Content : 97.0 per cent to 103.0 per cent of CaCl2,6H2O. CHARACTERS Appearance : white or almost white, crystalline mass or colourless crystals. Solubility : very soluble in water, freely soluble in ethanol (96 per cent). It solidifies at about 29 °C. IDENTIFICATION A. Solution S (see Tests) gives reaction (a) of chlorides (2.3.1). B. It gives the reactions of calcium (2.3.1). C. It complies with the limits of the assay. TESTS Solution S. Dissolve 15.0 g in carbon dioxide-free water R prepared from distilled water R and dilute to 100 mL with the same solvent. Appearance of solution. Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y6 (2.2.2, Method II). Acidity or alkalinity. To 10 mL of freshly prepared solution S add 0.1 mL of phenolphthalein solution R. If the solution is red, not more than 0.2 mL of 0.01 M hydrochloric acid is required to discharge the colour and if the solution is colourless, not more than 0.2 mL of 0.01 M sodium hydroxide is required to turn it red. Sulfates (2.4.13) : maximum 200 ppm. Dilute 5 mL of solution S to 15 mL with distilled water R. Aluminium. To 10 mL of solution S add 2 mL of ammonium chloride solution R and 1 mL of dilute ammonia R1. Heat to boiling. No turbidity or precipitate is formed. If intended for use in the manufacture of dialysis solutions, the above test is replaced by the following test for aluminium (2.4.17) : maximum 1 ppm. Prescribed solution. Dissolve 6 g in 100 mL of water R and add 10 mL of acetate buffer solution pH 6.0 R. Reference solution. Mix 2 mL of aluminium standard solution (2 ppm Al) R, 10 mL of acetate buffer solution pH 6.0 R and 98 mL of water R. Blank solution. Mix 10 mL of acetate buffer solution pH 6.0 R and 100 mL of water R. General Notices (1) apply to all monographs and other texts LABELLING The label states, where applicable, that the substance is suitable for use in the manufacture of dialysis solutions. 07/2008:1183 corrected 7.0 CALCIUM DOBESILATE MONOHYDRATE Calcii dobesilas monohydricus C12H10CaO10S2,H2O [20123-80-2] Mr 436.4 DEFINITION Calcium di(2,5-dihydroxybenzenesulfonate) monohydrate. Content : 99.0 per cent to 101.0 per cent (anhydrous substance). CHARACTERS Appearance : white or almost white, hygroscopic powder. Solubility : very soluble in water, freely soluble in anhydrous ethanol, very slightly soluble in 2-propanol, practically insoluble in methylene chloride. IDENTIFICATION A. Ultraviolet and visible absorption spectrophotometry (2.2.25). Test solution. Dissolve 0.100 g in water R and dilute to 200.0 mL with the same solvent. Dilute 5.0 mL of this solution to 100.0 mL with water R. Spectral range : 210-350 nm. Absorption maxima : at 221 nm and 301 nm. Specific absorbance at the absorption maximum at 301 nm : 174 to 181. B. Mix 1 mL of ferric chloride solution R2, 1 mL of a freshly prepared 10 g/L solution of potassium ferricyanide R and 0.1 mL of nitric acid R. To this mixture add 5 mL of freshly prepared solution S (see Tests) : a blue colour and a precipitate are immediately produced. 1733 wash the precipitate with 2 small quantities of acetone R and dry.8) : maximum 15 ppm.5 (anhydrous substance) DEFINITION Calcium (2S)-2-[[4-[[[(6RS)-2-amino-5-formyl-4-oxo1. Solubility : sparingly soluble in water.20).0 mL with water R. Solution S.4.0 mL of the test solution to 100. 1734 IMPURITIES Specified impurities : A. B. Dissolve 10 mg of the substance to be examined and 10 mg of hydroquinone R (impurity A) in water R and dilute to 10 mL with the same solvent.2 g of anhydrous sodium dihydrogen phosphate R in 900 mL of water for chromatography R. C. buffer solution (10:90 V/V). Related substances. Test solution. multiply the peak area of impurity A by 0.0 g complies with test C.4. when freshly prepared. Ar 40.0 per cent to 102.0 mL of this solution to 10.6. Dissolve 1. pH (2. A.0 g in carbon dioxide-free water R and dilute to 100 mL with the same solvent. IDENTIFICATION First identification : A. – total : not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (0. hygroscopic powder. is clear (2. A.4-diol (hydroquinone). Run time : 2.7. Test solution. – stationary phase : spherical end-capped octadecylsilyl silica gel for chromatography R (5 μm). not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2.6 mm .5 to 6. determined on 0. If the spectra obtained show differences.08) : 7.2. benzene-1.1). Keep all solutions at 2-8 °C.2. Relative retention with reference to dobesilate (retention time = about 6 min) : impurity A = about 1.7. 2 mL of freshly prepared solution S gives reaction (b) of calcium (2. C. Specific optical rotation (see Tests). Preparation : discs. Limits : – correction factor : for the calculation of content. Injection : 10 μL.2. D. Dissolve 0.0 CALCIUM FOLINATE Calcii folinas C20H21CaN7O7.0 between the peaks due to dobesilate and impurity A. Ø = 4.2. Appearance of solution.0 per cent.5 times the retention time of dobesilate. ASSAY Dissolve 0.27). practically insoluble in acetone and in ethanol (96 per cent). protected from light. See the information section on general monographs (cover pages) .1 M cerium sulfate.14 per cent (anhydrous substance). D.5.8 mL/min.5.1) and colourless (2. B.xH2O Mr 511.6 . Dissolve 10. determined on 10 mL of solution S. Second identification : A.200 g in a mixture of 10 mL of water R and 40 mL of dilute sulfuric acid R.0 mL with the same solvent. CHARACTERS Appearance : white or light yellow.54 per cent to 8. Infrared absorption spectrophotometry (2. Iron (2.0 mL with water R. Dissolve 15 mg of the substance to be examined in a 3 per cent V/V solution of ammonia R and dilute to 5 mL with the same solvent.10 per cent) . – unspecified impurities : for each impurity. Dilute 1. Method II). – impurity A : not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0. Water (2. Record new spectra using the residues. Reference solution (b).3. Liquid chromatography (2. determining the end-point potentiometrically (2. collect the precipitate by centrifugation. 1 mL of 0.0 C.2 per cent) .100 g of the substance to be examined in water R and dilute to 10. Column : – size : l = 0. 1. – calcium (Ca .4. Dilute 1. 01/2009:0978 corrected 7.2. – disregard limit : 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0. System suitability : reference solution (b) : – resolution : minimum 8. amorphous or crystalline.05 per cent).45 mg of C12H10CaO10S2. The amorphous form may produce supersaturated solutions in water.0 for solution S.5 mL of lead standard solution (10 ppm Pb) R. Prepare the reference solution using 1.0 per cent to 6. Heavy metals (2.29). Buffer solution. adjust to pH 6. Detection : spectrophotometer at 220 nm.500 g. Dilute 1 mL of this solution to 100 mL with water R. Content : – calcium folinate (C20H21CaN7O7): 97.1 per cent) .12) : 4.5 with disodium hydrogen phosphate solution R and dilute to 1000 mL with water for chromatography R. Allow to stand for 15 min.24). Reference solution (a). Flow rate : 0.2. Thin-layer chromatography (2.8-hexahydropteridin-6-yl]methyl]amino]benzoyl]amino]pentanedioate.2.0 per cent (anhydrous substance) .25 m. Comparison : calcium folinate CRS. TESTS Solution S.9) : maximum 10 ppm. dissolve the substance to be examined and the reference substance separately in the minimum volume of water R and add dropwise sufficient acetone R to produce a precipitate. STORAGE In an airtight container. Mobile phase : acetonitrile R1.3): 4. It contains a variable quantity of water.1 M cerium sulfate is equivalent to 10.Calcium folinate EUROPEAN PHARMACOPOEIA 8. Titrate with 0.