Determination of selenium sulfide using 1,3-dibromo-5,5-dimethylhydantoin (DBH). Analytical methods of pharmacopeias with DBH in respect to environmental and economical concern Part 11

USP 2000 (The United States Pharmacopeia, Rockville, MD, 24th ed., 2000, pp. 1514-1515) and PH. EUR. 1997 (European Pharmacopoeia, 3rd ed., Council of Europe, Strasbourg, 1997, p. 1459) dissolve selenium sulfide by boiling with fuming nitric acid for about 1 h. After cooling to room temperature and dilution with water nitrous acid and nitrogen oxides are removed with urea also by boiling before the iodometric titration is performed. This method can be importantly simplified and improved, when using 1,3-dibromo-5,5-dimethylhydantoin (DBH) in glacial acetic acid in presence of solid potassium bromide. Selenium sulfide is dissolved during 5-10 min at room temperature. The excess of DBH and bromine can be removed with 5-sulfosalicylic acid also without boiling. The point of the indicator change for the iodometric titration is improved in comparison to the method of the pharmacopeias, because the colloidal solution of selenium mostly coagulates. Also the sulfur content of selenium sulfide can be determined with DBH.     

Determination of iodine values using 1,3-dibromo-5,5-dimethylhydantoin (DBH) without the employment of chlorinated hydrocarbons. Analytical methods of pharmacopoeias with DBH in respect to environmental and economical concern. Part 17

Low and medium iodine values of fixed oils and fats can be determined in glacial acetic acid within reduced waiting times of only 5 min. Highly unsaturated compounds such as those of linseed oil, cod-liver oil, sunflower oil, soybean oil, wheat germ oil and the emulsifier sorbitan trioleate result too low values in comparison to PH. EUR. 2002 [2] and USP 2000 [3]. Cocoa butter with a low iodine number is insoluble in glacial acetic acid. The iodine values of nonionogenic emulsifiers such as ceteareth-30 (Macrogol cetostearyl ether PH. EUR. 2002), oleth-10 resp. 20 (Macrogol oleyl ether PH. EUR. 2002) and polysorbate-80 PH. EUR. 2002 are obtained in aqueous solutions. Oleth-2 (Macrogol oleyl ether PH. EUR. 2002), polyoxyl-40 castor oil (Macrolglycerol ricinoleate PH. EUR. 2002), polysorbate-60 PH. EUR. 2002 and sorbitan trioleate PH. EUR. 2002 need the addition of ethyl acetate. Fixed oils even with high iodine values can be determined in an o/w emulsion with a reaction time of 5 min in most cases, when nonionogenic emulsifiers such as ceteareth-30, polyoxyl-30 glycerol monolaurate or polyoxyl-60 hydrogenated castor oil (Macrolglycerol hydroxystearate PH. EUR. 2002) are used.     

Determination of iron limiting values according to PH. EUR. using 1,3-dibromo-5,5-dimethylhydantoin (DBH) instead of elemental bromine. Analytical methods of pharmacopoeias with DBH in respect to environmental and economical concern. Part 8

PH. EUR. 2002 uses elemental bromine performing iron limit tests for maleic acid (iron 5 ppm) and titanium dioxide (iron 200 ppm). 1,3-Dibromo-5,5-dimethylhydantoin (DBH) can replace bromine water. For the iron limit test of maleic acid bivalent iron is oxidized to trivalent iron by bromine resp. DBH, because the unsaturated, in high concentration existing acid reacts substantially slower. On the other hand maleic acid removes the excess of bromine. The bromine oxidation for the iron limiting values of titanium dioxide according to the pharmacopoeia is not required. Metallic iron as well as ferrous salts are converted to trivalent iron, when the titanium test solution is prepared by boiling with concentrated sulphuric acid in the presence of anhydrous sodium sulphate.     

Determination of iodide with 1,3-dibromo-5,5-dimethylhydantoin (DBH) in comparison with the ICl-method. Analytical methods of pharmacopeias with DBH in respect to environmental and economical concern. Part 3

USP 1995 (The United States Pharmacopeia, 23rd Edit., (1995), potassium iodide p. 1265, sodium iodide p. 1424), PH. EUR. 1997 (European Pharmacopoeia, third ed., Council of Europe, Strasbourg, (1997), potassium iodide p. 1367, sodium iodide p. 1493) and JAP 1996 (The Japanes Pharmacopoeia, 13th ed. (1996), potassium iodide p. 578, sodium iodide p. 630) determine iodide with the ICl-method (J. Am. Chem. Soc. 25 (1903) 756-761; Z. Anorg. Chem. 36 (1903) 76-83; Fresenius Z. Anal. Chem. 106 (1936) 12-23; Arzneibuch-Kommentar, Wissenschaftliche Erl?uterungen zum Europ?ischen Arzneibuch, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, Govi-Verlag - Pharmazeutischer Verlag GmbH, Eschborn, 12th suppl. (1999), K10 p. 2), using chloroform, which is toxic and hazardous to environment. Without the application of chlorinated hydrocarbons USP 2000 (The United State Pharmacopeia, 24th ed. (2000), potassium iodide p. 1368, sodium iodide p. 1535) and Brit 1999 (British Pharmacopoeia London, (1999), Appendix VIII C, p. A162) titrate iodide with the redox indicator amaranth. A titration with potentiometric indication giving two end-points at the step of I(2) and [ICl(2)](-) is described. Due to the high concentration of hydrochloric acid required for the ICl-method, the determination with DBH (1,3-dibromo-5,5-dimethylhydantoin; 1,3-dibromo-5,5-dimethyl-2,4-imidazolidinedione) can be recommended and is performed easily. Similarly, the iodide content of gallamine triethiodide may be analyzed with DBH by application of a visual two-phase titration in water and ethyl acetate or with potentiometric indication in a mixture of 2-propanol and water. During the removal of the excess of DBH 4-bromo-triethylgallamine (2,2',2"-[1-bromo-benzene-2,3,4-triyltris(oxy)]N,N,N-triethylethanium) is formed.     

Determination of iodine values using 1,3-dibromo-5,5-dimethylhydantoin (DBH) and ethyl acetate as solvent. Analytical methods with DBH in respect to environmental and economical concern, part 18

Iodine values (iodine numbers) of several fixed oils and lard can be determined in ethyl acetate, an easily biodegredable solvent, instead of chloroform according to PH. EUR. 2002. Iodine monobromide has been replaced by 1,3-dibromo-5,5-dimethylhydantoin (DBH) and potassium iodide (KI) and the reaction time was reduced to 5 min only. However, cod-liver oil and linseed oil require a reaction time of 30 min and a smaller weight of sample. Longer reaction times are also necessary for soya oil and wheat germ oil. Iodine values of linseed oil determined according to method A of PH. EUR. 2002, are dependent on the amount of sample, even in the range prescribed by the pharmacopoeia.     

Determination of propylthiouracil using 1,3-dibromo-5,5-dimethylhydantoin (DBH): analytical methods of pharmacopeias with DBH in respect to environmental and economical concern: part 9

USP 2000 [The United States Pharmacopeia, Rockville USA, 24th ed., 2000, pp. 1436] and PH. EUR. 1997 [European Pharmacopoeia, third ed., Council of Europe, Strasbourg, 1997, p. 1401] determine propylthiouracil using neutralization titration, whereby 0.1 M silver nitrate and twice boiling is necessary. With the application of 1,3-dibromo-5,5-dimethylhydantoin (DBH), the assay of propylthiouracil can be performed easily, faster and friendlier to environment. A mean deviation of 0.03% and a relative standard deviation of 0.3% are obtained. 5-Bromo-6-propyluracil is formed, when propylthiouracil is determined with DBH.     

Cetylpyridinium tetrachlorozincate as standard for tenside titration. Analytical methods with 1,3-dibromo-5,5-dimethylhydantoin (DBH) in respect to environmental and economical concern, part 19

The determination of the cationic active disinfectants benzalkonium chloride, benzethonium chloride, cetrimide, and cetylpyridinium chloride according to PH. EUR. 2002 resp. supplement 4.3/2003 can be improved using the DBH-method. By application of column extraction the iodide determination can be performed in the organic layer by visual indication. However, titration in aqueous solution with sodium dodecyl sulphate as titrant and methyl orange resp. bromophenol blue as indicator can be performed more simple. Cetylpyridinium tetrachlorozincate is recommended as a standard for tenside titration.     

Application of 1,3-dibromo-5,5-dimethylhydantoin (DBH) instead of bromine gas or bromine water decolorization for drug identification according to PH. EUR. Analytical methods of pharmacopoeias with DBH in respect to environmental and economical concern,Part 14

PH. EUR. 2002 identifies biotin, flucytosine, polysorbate 80 and sorbic acid using the decolorization of bromine water. These tests can be better performed with 1,3-dibromo-5,5-dimethylhydantoin (DBH) in combination of the reaction with fluorescein sodium resp. sodium bromide. Also fluorescein sodium PH. EUR. Suppl 2002 can be identified with DBH.     

1,3-Dibromo-5,5-dimethylhydantoin (DBH) as oxidant and precipitant for drug identification according to PH. EUR Analytical methods of pharmacopoeias with DBH in respect of environmental and economical concern,Part 15(1)

Elemental bromine serves as oxidant for the identification of propylthiouracil, 2-thiouracil and sulphur according to PH. EUR. 2002. Phenol is identified according to PH. EUR. 2002 with bromine water as the sparingly water-soluble 2,4,4,6-tetrabromo-2,5-cyclohexadiene-1-one. These tests can be performed better using 1,3-dibromo-5,5-dimethylhydantoin (DBH).     

Identification of lactate. Analytical methods of pharmacopoeias with DBH in respect to environmental and economical concern, Part 4

The identification of lactate according to Ph. Eur. 1997 and DAB 2000 uses the oxidation of lactic acid to pyruvic acid by boiling with bromine water in sulphuric acid. Acetaldehyde arising by decarboxylation is detected according to Legal applying a time consuming and troublesome procedure. 1,3-Dibromo-5,5-dimethylhydantoin (DBH) as well as potassium bromate can replace elemental bromine. Lactic acid and all lactates of Ph. Eur. 1997 and DAB 2000 can be identified better and faster using lactate oxidase (LOD, test strip system Accusport). According to DAB 2000 the base of ethacridine lactate has to be separated. This is no longer necessary, if an enzymatic identification is applied.     

Determination of organically bound iodine by reductive mineralization with aluminium powder. Analytical methods of pharmacopoeias with DBH in respect to environmental and economical concern. Part 16

PH. EUR. 2002, JAP 1996 and USP 2000 mineralize organically bound iodine in x-ray contrast media by boiling under reflux with zinc powder in alkaline solution. The reductive mineralization can be performed at room temperature without filtration, when aluminium powder is used. Resulting iodide is titrated by argentometry and potentiometric indication according to the pharmacopoeia or after oxidation with 1,3-dibromo-5,5-dimethylhydantoin by iodometry.     

Determination of iodine values according to Hanus using 1,3-dibromo-5,5-dimethylhydantoin (DBH): analytical methods of pharmacopeias with DBH: part 7

USP/NF 2000 [The United States Pharmacopeia, Rockville USA, 24th ed., 2000, p. 1868, The National Formulary, 19th ed. 2000] and PH. EUR. 1997 [European Pharmacopoeia, third ed., Council of Europe, Strasbourg, 1997, pp. 63-64] determine the iodine values according to Hanus with iodine monobromide in glacial acetic acid. This reagent can be replaced by a solution of 1,3-dibromo-5,5-dimethylhydantoin (DBH) and potassium iodide or iodine in the same solvent. Both reagents yield equivalent results by means of method comparison according to Passing and Bablok [J. Clin. Chem. Clin. Biochem. 21 (1983) 709; 22, (1984) 431] in relation to the official method of PH. EUR.     

Determination of peroxide values using ethyl acetate as solvent. Analytical methods in respect to environmental and economical concern, part 21

Peroxide values of fixed oils can be determined in ethyl acetate, an easily biodegredable solvent instead of chloroform according to PH. EUR. 2002, method A. Potentiometric indication is recommended. Further investigations are necessary to explain the high blank values obtained, when ethyl acetate is used.     

Determination of anionactive tensides using cetylpyridinium tetrachlorozincate as titrant. Analytical methods in respect to environmental and economical concern, part 20

Sodium lauryl sulphate (sodium dodecylsulphate) can be determined in aqueous medium using cetylpyridinium tetrachlorozincate as standard solution and methyl orange resp. bromophenol blue as indicator. However, the determination of cetostearyl sulphate is problematic due to its slight solubility in cold water. Therefore, the titration has to be performed in warm solution. As well with methyl orange as with bromophenol blue the change of the indicator has to be titrated to colour shade. A photometric detection is recommended. The visual indication concerning the determination of the content of the technical solutions of the secondary paraffin sulphonates such as Ateban TH liquid and Marlon PS 30 is also critical.     

Synthesis and biological studies of 3-(beta-D-ribofuranosyl)-2,3,-dihydro-6H-1,3-oxazine-2,6-dione, a new pyrimidine nucleoside analog related to uridine.

Reaction of the trimethylsilyl derivative of 2,3-dihydro-6H-1,3-oxazine-2,6-dione (2, "uracil anhydride") with protected 1-O-acetylribofuranoses in the presence of stannic chloride gave the corresponding block nucleosides. 3-(2,3-5-Tri-O-2',2',2'-trichloroethoxycarbonyl-beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (4c) thus prepared from the protected sugar 3c, 1-O-acetyl-2,3,5-tri-O-(2,2,2-trichloroethoxycarbonyl)ribofuranose, gave, on removal of the protecting groups with zinc dust,3-(beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (1). The structure of 1 was confirmed by uv, ir, NMR, and CD spectral data and was shown to be an N nucleoside. Uracil anhydride, 2, and, to a lesser extent, its ribonucleoside 1 exert a moderate growth inhibition of mouse leukemia L5178Y, HeLa, and Novikoff hepatoma cells i- culture. Both compounds produce weak inhibition of vaccinia viral replication in HeLa cells.