氟他胺EP7.0药典标准[1]

Flutamide EUROPEAN PHARMACOPOEIA 7.0 Detection : spectrophotometer at 250 nm. Injection : 10 μL. Identification of impurities : use the chromatogram obtained with reference solution (a) to identify the peak due to impurity C. Relative retention with reference to fluspirilene (retention time = about 15 min) : impurity A = about 0.8 ; impurity B = about 0.93 ; impurity C = about 0.97. System suitability : reference solution (a) : — resolution : minimum 2.2 between the peaks due to impurity C and fluspirilene. Limits : — impurities A, B, C : for each impurity, not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent), — unspecified impurities : for each impurity, not more than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.10 per cent), — total : not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.6 per cent), — disregard limit : 0.25 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent). Loss on drying (2.2.32) : maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 °C for 4 h. Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on 1.0 g in a platinum crucible. ASSAY Dissolve 0.350 g in 50 mL of a mixture of 1 volume of anhydrous acetic acid R and 7 volumes of methyl ethyl ketone R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20). Carry out a blank titration. 1 mL of 0.1 M perchloric acid is equivalent to 47.56 mg of C29H31F2N3O. STORAGE Protected from light. IMPURITIES Specified impurities : A, B, C. A. R1 = R2 = R3 = H: 8-[(4RS)-4-(4-fluorophenyl)-4-phenylbutyl]- 1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, B. R1 = R3 = H, R2 = F: 8-[(4RS)-4-(2-fluorophenyl)-4-(4- fluorophenyl)butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4- one, C. R1 = CH2OH, R2 = H, R3 = F: 8-[4,4-bis(4-fluorophenyl)butyl]- 3-(hydroxymethyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one. 01/2008:1423 FLUTAMIDE Flutamidum C11H11F3N2O3 Mr 276.2 [13311-84-7] DEFINITION 2-Methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide. Content : 97.0 per cent to 103.0 per cent (dried substance). CHARACTERS Appearance : pale yellow, crystalline powder. Solubility : practically insoluble in water, freely soluble in acetone and in ethanol (96 per cent). mp: about 112 °C. IDENTIFICATION Infrared absorption spectrophotometry (2.2.24). Comparison : flutamide CRS. TESTS Related substances. Liquid chromatography (2.2.29). Test solution. Dissolve 20.0 mg of the substance to be examined in the mobile phase and dilute to 20.0 mL with the mobile phase. Reference solution (a). Dissolve 2 mg of flutamide CRS and 2 mg of flutamide impurity C CRS in the mobile phase, then dilute to 50.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 20.0 mL with the mobile phase. Reference solution (b). Dilute 1.0 mL of the test solution to 50.0 mL with the mobile phase. Dilute 2.0 mL of this solution to 20.0 mL with the mobile phase. Column : — size : l = 0.25 m, Ø = 4.0 mm; — stationary phase : octadecylsilyl silica gel for chromatography R (5 μm). Mobile phase : acetonitrile R, water R (50:50 V/V). Flow rate : 0.5 mL/min. Detection : spectrophotometer at 240 nm. Injection : 20 μL. Run time : 1.5 times the retention time of flutamide. Retention time : impurity C = about 14 min ; flutamide = about 19 min. Relative retention with reference to flutamide : impurity C = about 0.72. System suitability : reference solution (a) : — resolution : minimum 10.5 between the peaks due to impurity C and flutamide. Limits : — impurity C : not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent) ; — impurities A, B, D, E, F : for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent) ; — total : not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent) ; — disregard limit : 0.25 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent). Heavy metals (2.4.8) : maximum 20 ppm. 1.0 g complies with test C. Prepare the reference solution using 2 mL of lead standard solution (10 ppm Pb) R. Loss on drying (2.2.32) : maximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 60 °C for 3 h. Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on 1.0 g. ASSAY Dissolve 25.0 mg in methanol R and dilute to 25.0 mL with the same solvent. Dilute 2.0 mL of this solution to 100.0 mL with methanol R. Measure the absorbance (2.2.25) at the absorption maximum at 295 nm. 2058 See the information section on general monographs (cover pages) EUROPEAN PHARMACOPOEIA 7.0 Fluticasone propionate Calculate the content of C11H11F3N2O3 taking the specific absorbance to be 295. STORAGE Protected from light. IMPURITIES Specified impurities : A, B, C, D, E, F. A. R = H, R′ = NO2: 4-nitro-3-(trifluoromethyl)aniline, B. R = CO-CH3, R′ = NO2 : N-[4-nitro-3-(trifluoromethyl)- phenyl]acetamide, C. R = CO-CH2-CH3, R′ = NO2: N-[4-nitro-3-(trifluoro- methyl)phenyl]propanamide, D. R = R′ = H: 3-(trifluoromethyl)aniline, E. R = H: 2-methyl-N-[3-(trifluoromethyl)phenyl]propanamide, F. R = NO2: 2-methyl-N-[2-nitro-5-(trifluoromethyl)- phenyl]propanamide. 01/2008:1750 FLUTICASONE PROPIONATE Fluticasoni propionas C25H31F3O5S Mr 500.6 [80474-14-2] DEFINITION 6α,9-Difluoro-17-[[(fluoromethyl)sulfanyl]carbonyl]-11β- hydroxy-16α-methyl-3-oxoandrosta-1,4-dien-17α-yl propanoate. Content : 97.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance : white or almost white powder. Solubility : practically insoluble in water, sparingly soluble in methylene chloride, slightly soluble in alcohol. IDENTIFICATION A. Infrared absorption spectrophotometry (2.2.24). Comparison : fluticasone propionate CRS. B. Examine the chromatograms obtained in the assay. Results : the principal peak in the chromatogram obtained with the test solution is similar in retention time to the principal peak in the chromatogram obtained with reference solution (b). TESTS Specific optical rotation (2.2.7) : + 32 to + 36 (anhydrous substance). Dissolve 0.25 g in methylene chloride R and dilute to 50.0 mL with the same solvent. Related substances. Liquid chromatography (2.2.29) : use the normalisation procedure. Test solution. Dissolve 20 mg of the substance to be examined in a mixture of equal volumes of mobile phase A and mobile phase B and dilute to 100.0 mL with the same mixture of mobile phases. Reference solution (a). Dissolve 4 mg of fluticasone impurity D CRS in a mixture of equal volumes of mobile phase A and mobile phase B and dilute to 100.0 mL with the same mixture of mobile phases. Reference solution (b). Dissolve 20 mg of fluticasone propionate CRS in a mixture of equal volumes of mobile phase A and mobile phase B, add 1.0 mL of reference solution (a) and dilute to 100.0 mL with a mixture of equal volumes of mobile phase A and mobile phase B. Column : — size : l = 0.25 m, Ø = 4.6 mm, — stationary phase : octadecylsilyl silica gel for chromatography R (5 μm), — temperature : 40 °C. Mobile phase : — mobile phase A : a solution containing 0.05 per cent V/V of phosphoric acid R and 3.0 per cent V/V of methanol R in acetonitrile R, — mobile phase B : a solution containing 0.05 per cent V/V of phosphoric acid R and 3.0 per cent V/V of methanol R in water R, Time (min) Mobile phase A (per cent V/V) Mobile phase B (per cent V/V) 0 - 40 43 → 55 57 → 45 40 - 60 55 → 90 45 → 10 60 - 70 90 10 70 - 75 90 → 43 10 → 57 Flow rate : 1 mL/min. Detection : spectrophotometer at 239 nm. Injection : 50 μL; inject the test solution and reference solution (b). Relative retention with reference to fluticasone propionate (retention time = about 30 min) : impurity A = about 0.38 ; impurity B = about 0.46 ; impurity C = about 0.76 ; impurity D = about 0.95 ; impurity E = about 1.12 ; impurity F = about 1.18 ; impurity G = about 1.33 ; impurity H = about 1.93 ; impurity I = about 2.01. System suitability : reference solution (b) : — resolution : minimum 1.5 between the peaks due to impurity D and to fluticasone propionate. Limits : — impurities D, G : for each impurity, maximum 0.3 per cent, — impurities A, B, C, E, F, H, I : for each impurity, maximum 0.2 per cent, — impurity with relative retention at about 1.23 : maximum 0.2 per cent, — any other impurity : maximum 0.1 per cent, — total : maximum 1.2 per cent, — disregard limit : 0.05 per cent. Acetone. Gas chromatography (2.2.28). Internal standard solution. Dilute 0.5 mL of tetrahydrofuran R to 1000 mL with dimethylformamide R. Test solution. Dissolve 0.50 g of the substance to be examined in the internal standard solution and dilute to 10.0 mL with the same solution. Reference solution. Dilute 0.40 g of acetone R to 100.0 mL with the internal standard solution. Dilute 1.0 mL to 10.0 mL with the internal standard solution. General Notices (1) apply to all monographs and other texts 2059 2_Volume2_E.pdf 31-F-E toc Fluspirilenum TESTS Loss on drying (2.2.32): maximum 0.5 per cent, determined on 1.0 Sulfated ash (2.4.14): maximum 0.1 per cent, determined on 1.0 g ASSAY STORAGE IMPURITIES Flutamide Flutamidum DEFINITION CHARACTERS IDENTIFICATION TESTS Related substances. Liquid chromatography (2.2.29). Heavy metals (2.4.8): maximum 20 ppm. Loss on drying (2.2.32): maximum 0.5 per cent, determined on 1.0 Sulfated ash (2.4.14): maximum 0.1 per cent, determined on 1.0 g ASSAY STORAGE IMPURITIES Fluticasone propionate Fluticasoni propionas DEFINITION CHARACTERS IDENTIFICATION TESTS Specific optical rotation (2.2.7): + 32 to + 36 (anhydrous subst Related substances. Liquid chromatography (2.2.29): use the norm Acetone. Gas chromatography (2.2.28).