马来酸氯苯那敏BP2015翻译

毒手药王邓智先

Chlorphenamine Maleate 马来酸氯苯那敏
General Notices 总体概述
(Ph. Eur. monograph 0386)

C20H23ClN2O4 390.9 113-92-8 Action and use 使用及用途
Histamine H1 receptor antagonist; antihistamine. 组胺H1受体拮抗剂；抗组胺药。 Preparations 制剂
Chlorphenamine Injection 马来酸氯苯那敏注射液
Chlorphenamine Oral Solution 马来酸氯苯那敏口服溶液 Chlorphenamine Tablets 马来酸氯苯那敏片 Ph Eur
DEFINITION 定义
(3RS)-3-(4-Chlorophenyl)-N,N-dimethyl-3-(pyridin-2-yl)propan-1-amine hydrogen (Z)- butenedioate. （3RS）-3-（4-氯苯基）-N，N-二甲基-3 -（2-吡啶基）丙烷-1-胺氢（Z）—butenedioate。 Content 含量
98.0 per cent to 101.0 per cent (dried substance). 98.0~101.0%（按干燥品计算） CHARACTERS 性状
Appearance 外观
White or almost white, crystalline powder. 白色或类白色结晶性粉末 Solubility 溶解度
Freely soluble in water, soluble in ethanol (96 per cent). 易溶于水，溶于乙醇（96.0%） IDENTIFICATION

鉴别
A. Melting point (2.2.14): 130 °C to 135 °C.熔点（2.2.14）130℃-135℃
B. Infrared absorption spectrophotometry (2.2.24).Comparison chlorphenamine maleate CRS. 红外光吸收光谱（2.2.24）与马来酸氯苯那敏的对照品一致 C. Optical rotation (see Tests).旋光度（见测试） TESTS 测试
Solution S
溶液澄清度与颜色（溶液S）
Dissolve 2.0 g in water R and dilute to 20.0 mL with the same solvent. 取供试品2.0g，置于20ml容量瓶中，用水溶解并稀释至刻度。 Appearance of solution溶液外观
Solution S is clear (2.2.1) and not more intensely coloured than reference solution BY6(2.2.2, Method II).溶液S应澄清无色；如显色，与BY6比较不得更深。 Optical rotation (2.2.7)旋光度 -0.10° to + 0.10°, determined on solution S.-0.10°-+0.10°，用溶液S测定 Related substances有关物质
Liquid chromatography (2.2.29).高效液相色谱法(2.2.29)
Test solution Dissolve 0.100 g of the substance to be examined in the mobile phase and dilute to 100.0 mL with the mobile phase.
供试品溶液：精密称取供试品0.100g，置100ml容量瓶中，用流动相溶解并定量稀释至刻度，即得。
Reference solution (a) Dilute 0.5 mL of the test solution to 100.0 mL with the mobilephase.
对照溶液a:精密量取供试品溶液0.5ml置100ml容量瓶中，用流动相定量并稀释至刻度，即得。
Reference solution (b) Dilute 1.0 mL of reference solution (a) to 10.0 mL with the mobile phase.
对照溶液b:精密量取对照溶液a1.0ml,置10ml容量瓶中，用流动相定量并稀释至刻度，即得。
Reference solution (c) Dissolve 5 mg of chlorphenamine impurity C CRS in 5 mL of the test solution and dilute to 50.0 mL with the mobile phase. Dilute 2 mL of this solutionto 20 mL with the mobile phase.
对照溶液c：精密量取杂质C 对照品5mg，置50.0ml容量瓶中，用5ml的供试品溶液溶解，加入流动相溶解并稀释至刻度，摇匀。再取该溶液2ml置20ml容量瓶中，并用流动相溶解并稀释至刻度，即得。
Reference solution (d) Dissolve 5 mg of 2,2¢-dipyridylamine R (impurity B) in the mobile phase and dilute to 100 mL with the mobile phase.
对照溶液d:精密量取5mg的杂质B 置100ml的容量瓶中，用流动相溶解并定量稀释至刻度即得。
Reference solution (e) Dissolve the contents of a vial of chlorphenamine impurity A CRS in 2 mL of the test solution. Sonicate for 5 min.
对照溶液e:精密量取含有杂质A的对照品，用2ml的供试品溶液溶解，超声5分钟。 Column:柱
— size: l = 0.30 m, Ø = 3.9 mm;尺寸


— stationary phase: octadecylsilyl silica gel for chromatography R (10 μm).固定相：十八烷基硅胶色谱（10μm）
Mobile phase Mix 20 volumes of acetonitrile R and 80 volumes of a 8.57 g/L solution of ammonium dihydrogen phosphate R previously adjusted to pH 3.0 with phosphoric acid R.
流动相：乙腈-磷酸二氢铵溶液8.57g/L（事先用磷酸调节pH至3.0）（20：80） Flow rate 1.2 mL/min.流速：1.2ml/min
Detection Spectrophotometer at 225 nm.分光光度计检测波长225nm Injection 20 μL.进样体积20μl
Run time 3.5 times the retention time of chlorphenamine.运行时间为氯苯那敏保留时间的3.5倍
Relative retention 相对保留时间
With reference to chlorphenamine (retention time = about 11 min): maleic acid = about 0.2; impurity A = about 0.3;  impurity B = about 0.4;  impurity C = about 0.9;  impurity D = about 3.0. 马来酸约0.2； 杂质A约0.3； 杂质B= 0.4； 杂质C约0.9； 杂质D约3.0。
System suitability: reference solution (c):
— resolution: minimum 1.5 between the peaks due to impurity C and chlorphenamine.
系统适用性溶液（对照溶液c）
分辨率：杂质C和氯苯那敏色谱峰之间的分离度应大于1.5 Limits: 限度
— correction factors: for the calculation of contents, multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 1.5; impurity B= 1.4;
校正因子：对于含量的计算，通过以下杂质的峰面积乘以相应的校正因子：杂质A= 1.5；杂质B= 1.4；
— impurity A: not more than 0.4 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent); 杂质A：不得大于对照溶液a所得图谱中主峰面积的0.4倍（0.2%）  
— impurities B, C, D: for each impurity, not more than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 per cent);
杂质B、C、D：任一杂质，不得大于对照溶液a所得图谱中主峰面积的0.2倍(0.1%)  
— unspecified impurities: for each impurity, not more than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per


cent);
其他杂质：不得大于对照溶液a所得图谱中主峰面积的0.2倍
— total: not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent);
总杂质：不得大于对照溶液a得到的主峰面积（0.5%）
— disregard limit: the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent); disregard the peaks due to the blank and maleic acid.
在色谱图中由溶液b得到的色谱峰面积（0.05%）可忽略不及；空白和马来酸的峰可忽略不计。
Heavy metals (2.4.8)重金属 Maximum 20 ppm.≤20ppm
1.0g complies with test C. Prepare the reference solution using 2 mL of lead standard solution (10 ppm Pb) R.
1.0g符合测试C.用2ml标准铅溶液作为对照溶液（10ppm Pb） Loss on drying (2.2.32)干燥失重
Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 °C for 4 h. ≤0.5%,取供试品1.000g，在105℃干燥4小时。 Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g. 硫酸灰分
≤0.1%,取供试品1.0g ASSAY
Dissolve 0.150 g in 25 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid , determining the end-point potentiometrically (2.2.20). 测定
精密称取0.150g的供试品用25ml无水乙酸溶解,用0.1M的高氯酸滴定，用电位指示终点。 1 mL of 0.1 M perchloric acid is equivalent to 19.54 mg of C20H23ClN2O4. 1ml的0.1M的高氯酸相当于19.54mg的C20H23ClN2O4 STORAGE
Protected from light. 储存 避光保存
IMPURITIES杂质 Specified impurities : A, B, C, D.

A. 2-(4-chlorophenyl)-4-(dimethylamino)-2-[2-(dimethylamino)ethyl]butanenitrile,










B. N-(pyridin-2-yl)pyridin-2-amine (2,2¢-dipyridylamine),

C. (3RS)-3-(4-chlorophenyl)-N-methyl-3-(pyridin-2-yl)propan-1-amine,

D. (2RS)-2-(4-chlorophenyl)-4-(dimethylamino)-2-(pyridin-2-yl)butanenitrile. Ph Eur
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