氢溴酸右美沙芬有关物质的测定  

Determination of related substances in dextromethorphan hydrobromide

作　　者：费路华 费瀚雨[2] 聂小春 

机构地区：[1]武汉药品医疗器械检验所,武汉430075 [2]华中科技大学同济医学院药学院,武汉430030

出　　处：《药物分析杂志》2015年第7期1250-1256,共7页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的：建立氢溴酸右美沙芬有关物质的检查方法。方法：采用比旋度法控制氢溴酸右美沙芬的左旋异构体杂质,采用HPLC法测定其他有关物质。色谱条件：采用Agilent Zobax SB-C18色谱柱（4.6 mm×250 mm,5μm）,以含20 mmol·L-1十二烷基硫酸钠的乙腈-水（600∶400）溶液（用冰醋酸调节p H至2.0）为流动相,流速1.0m L·min-1,检测波长280nm,柱温30℃,进样量20μL。结果：比旋度法能较好控制左美沙芬的限量,3批样品的测定结果均为＋25.6°。在所采用的液相色谱条件下,氢溴酸右美沙芬与各杂质均可良好分离;N,N-二甲基苯胺、杂质Ⅰ、杂质Ⅱ、3-甲氧基-10-羰基-17-甲基吗啡喃、N-氧化盐酸右美沙芬、氢溴酸右美沙芬和3-甲氧基吗啡喃质量浓度分别在0.84∽26.83μg·m L-1（r=0.999 9）、0.67∽21.70μg·m L-1（r=0.999 9）、0.61∽19.64μg·m L-1（r=0.999 9）、0.67∽21.35μg·m L-1（r=1.000 0）、0.67∽21.45μg·m L-1（r=0.999 6）、0.66∽21.03μg·m L-1（r=0.999 9）和0.63∽20.18μg·m L-1（r=1.000 0）范围内与峰面积呈良好的线性关系,其最低检测限分别为3、7、6、0.3、7、7和6 ng;3批样品中杂质Ⅰ、杂质Ⅱ、3-甲氧基-10-羰基-17-甲基吗啡喃及N-氧化盐酸右美沙芬均未检出,3-甲氧基吗啡喃的量分别为0.05%、0.05%、0.03%,最大单个未知杂质量分别为0.01%、0.01%、0.12%,杂质总量分别为0.07%、0.07%、0.15%。结论：本法经方法学验证可用于氢溴酸右美沙芬的有关物质检测和质量控制。Objective：To establish a method for determination of the related substances in dextromethorphan hydrobromide. Methods： Levomethorphan （ enantiomer of dextromethorphan hydrobromide） was controlled by spe- cific optical rotation, and other related substances were determined by HPLC. The determined condition of HPLC was performed on a Agilent Zobax SB-C18 column（4.6 mm × 250 mm, 5 μm）, using the mixture of acetonitrile- water（600：400 ）containing 20 mmol · L-1 sodium laurylsulfate （adjusted to pH 2.0 with glacial acetic acid）as the mobile phase. The flow rate was 1.0 mL· min - 1, the detection wavelength was 280 nm, the temperature of the column was 30 ℃, and the injection volume was 20μL. Results：The limited quantity of levomethorphan can be controlled by specific optical rotation and the results of three samples were all about 25.6%. Under the optimized condition of HPLC chromatograph, an excellent separation was achieved for dextromethorphan hydrobromide and the impurities. The calibration curves for N, N-dimethylaniline, impurity I , impurity 11 , 3-methoxy-17-methyl- morphinan-10- one, dextromethorphan N- oxide hydrochloride, dextromethorphan hydrobromide and 3 - methoxy- morphinan revealed good linearities over the range of 0. 84 - 26.83 μg·mL-1 （ r = 0. 999 9 ）, 0. 67 - 21.70μg·mL-1（r=0.9999）,0.61 -19.64 μg·mL-1（r=0.999 9）,0.67-21.35 μg·mL-1（r=l.000 0）, 0. 67 - 21.45 μg·mL-1 （ r = 0. 999 6 ）, 0. 66 - 21.03 μg·mL-1 （ r = 0. 999 9 ） and 0.63 - 20.18 μg·mL-1 （ r = 1. 000 0） ,respectively. The LODs of the above compounds were 3,7,6,0.3,7,7 and 6 ng ,respectively. In the determined three samples, the amounts of 3-methoxymorphinan were O. 05 % ,0.05% and 0.03 % ;the amounts of the maximum unknown individual impurity were 0.01% ,0.01% and 0. 12% ;the total amounts of impurity were 0.07 % , 0.07 % and 0.15 % , respectively. The other known impurity was not detected. Conclusion： The method is specific, accurate and sensitive, which can be used

关 键 词：氢溴酸右美沙芬 杂质检测 二甲基苯胺 杂质Ⅰ 杂质Ⅱ 甲氧基-羰基-甲基吗啡喃 氧化盐酸右美沙芬 左旋异构体 高效液相色谱法 比旋度法 

分 类 号：R917[医药卫生—药物分析学]