欧洲药典对乙酰氨基酚原料质量标准——有关物质检测(译文)

EP检测方法：Related substances. Liquid chromatography (2.2.29). Prepare the solutions immediately before use.Test solution. Dissolve 0.200 g of the substance to be examined in 2.5 mL of methanol R containing 4.6 g/L of a 400 g/L solution of tetrabutylammonium hydroxide R and dilute to 10.0 mL with a mixture of equal volumes of a 17.9 g/L solution of disodium hydrogen phosphate R and of a 7.8 g/L solution of sodium dihydrogen phosphate R.Reference solution (a). Dilute 1.0 mL of the test solution to 50.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 100.0 mL with the mobile phase.Reference solution (b). Dilute 1.0 mL of reference solution (a) to 10.0 mL with the mobile phase.Reference solution (c). Dissolve 5.0 mg of 4-aminophenol R,5 mg of paracetamol CRS and 5.0 mg of chloroacetanilide R in methanol R and dilute to 20.0 mL with the same solvent. Dilute 1.0 mL to 250.0 mL with the mobile phase.Reference solution (d). Dissolve 20.0 mg of 4-nitrophenol R in methanol R and dilute to 50.0 mL with the same solvent.Dilute 1.0 mL to 20.0 mL with the mobile phase.有关物质。

液相色谱(2.2.29)。

溶液临用现配。

供试品溶液：取0.200g的物质溶解在2.5ml甲醇溶液(含有400g/L的氢氧化四丁铵溶液4.6g/L)中，再用17.9 g/L 的磷酸氢二钠溶液和7.8 g/L磷酸二氢钠溶液的等体积混合液稀释至10ml。

对照溶液A：取供试品溶液1.0ml用流动相稀释至50ml，再取该溶液5.0ml稀释至100.0ml。

对照溶液B：取对照溶液A 1.0ml用流动相稀释至10ml。

对照溶液C：取5.0mg4-aminophenol对照品,5mgparacetamol CRS对照品和5.0mg chloroacetanilide对照品用甲醇溶解并稀释到20.0ml。

取1.0ml用流动相稀释至250.0ml。

对照溶液D：取20.0mg 4-nitrophenol对照品用甲醇溶解和稀释到50.0ml。

取1ml用流动相稀释至20ml。

Column:—size: l = 0.25 m, Ø = 4.6 mm,— stationary phase: octylsilyl silica gel for chromatography R(5 μm),— temperature: 35 °C.Mobile phase: mix 375 volumes of a 17.9 g/L solution ofdisodium hydrogen phosphate R, 375 volumes of a 7.8 g/Lsolution of sodium dihydrogen phosphate R and 250 volumesof methanol R containing 4.6 g/L of a 400 g/L solution oftetrabutylammonium hydroxide R.Flow rate: 1.5 mL/min.Detection: spectrophotometer at 245 nm.Injection: 20 μL.Run time: 12 times the retention time of paracetamol.Relative retentions with reference to paracetamol (retentiontime = about 4min) : impurity K = about 0.8 ; impurity F = about 3;impurity J = about 7.色谱柱:C-8色谱柱250mm*4.6mm*5μm柱温:35°C。

流动相:17.9g/L磷酸氢二钠:7.8g/L的磷酸二氢钠溶液:甲醇溶液(含400g/L的四丁基氢氧化铵4.6g/L)=375:375:250。

流量:1.5毫升/分钟。

检测波长245nm。

进样量:20μL。

运行时间:12倍扑热息痛的保留时间。

相对保留（参照对乙酰氨基酚，保留时间约4分钟):杂质K = 0.8;杂质F = 3;杂质J=7。

System suitability :reference solution (c) :— resolution: minimum 4.0 between the peaks due toimpurity K and to paracetamol,— signal-to-noise ratio : minimum 50 for the peak due toimpurity J.Limits :— impurity J : not more than 0.2 times the area of thecorresponding peak in the chromatogram obtained withreference solution (c) (10 ppm),— impurity K: not more than the area of the correspondingpeak in the chromatogram obtained with referencesolution (c) (50 ppm),— impurity F: not more than half the area of the correspondingpeak in the chromatogram obtained with referencesolution (d) (0.05 per cent),— any other impurity : not more than half the area of theprincipal peak in the chromatogram obtained with referencesolution (a) (0.05 per cent),— total of other impurities : not more than the area of theprincipal peak in the chromatogram obtained with referencesolution (a) (0.1 per cent),—disregard limit for the calculation of the total of other impurities : the area of the principal peak in thechromatogram obtained with reference solution (b) (0.01 percent).系统适用性:对照溶液(c):对乙酰氨基酚峰与杂质K之间分离度不得小于4.0,信噪比: 杂质J不得小于50.限度:——杂质J:不超过对照(c)相应峰的0.2倍(10 ppm),——杂质K: 不超过对照(c)相应峰(50ppm),——杂质F:不大于对照溶液(d)中相应峰面积的0.5倍(0.05%),——任何其他杂质:不大于对照溶液A中主峰面积的0.5倍(0.05%),——总其他杂质:不得大于对照溶液A中主峰面积(0.1%),——可忽略计算的杂质:峰面积小于杂质B中主峰面积的杂质(0.01%)A. R1 = R3 = R4 = H, R2 = OH: N-(2-hydroxyphenyl)acetamide,B. R1 = CH3, R2 = R3 = H, R4 = OH: N-(4-hydroxyphenyl)propanamide,C. R1 = R2 = H, R3 = Cl, R4 = OH: N-(3-chloro-4-hydroxyphenyl)acetamide,D. R1 = R2 = R3 = R4 = H: N-phenylacetamide,H. R1 = R2 = R3 = H, R4 = O-CO-CH3 : 4-(acetylamino)phenyl acetate,J. R1 = R2 = R3 = H, R4 = Cl: N-(4-chlorophenyl)acetamide (chloroacetanilide),E. X = O, R2 = H, R4 = OH: 1-(4-hydroxyphenyl)ethanone,G. X = N-OH, R2 = H, R4 = OH: 1-(4-hydroxyphenyl)ethanoneoxime,I. X = O, R2 = OH, R4 = H: 1-(2-hydroxyphenyl)ethanone,F. R = NO2: 4-nitrophenol,K. R = NH2: 4-aminophenol.。