硝西泮及其片剂中有关物质的液相色谱电喷雾质谱联用分析  

HPLC-MS determination of three impurities in nitrazepam and its tablets

作　　者：蔡梅[1] 刘菁[2,3] 蔡美明[1] 陈民辉[1] 王玉[1,2] 

机构地区：[1]江苏省食品药品检验所,南京210008 [2]中国药科大学,南京210009 [3]天津市药品检验所,天津300070

出　　处：《药物分析杂志》2012年第6期1028-1032,共5页Chinese Journal of Pharmaceutical Analysis

基　　金："十一五"国家科技支撑计划重点项目子课题(2008BAI55B05-001)

摘　　要：目的:建立HPLC-MS法测定硝西泮原料及片剂中3种杂质。方法:采用Shimadzu VP-ODS柱(250 mm×4.6 mm,5μm),以乙腈:10 mmol·L-1磷酸二氢钾(45:55)为流动相,流速1.0 mL·min-1,柱后分流;进样量10μL;DAD检测器,检测波长220 nm。电喷雾电离源(ESI),雾化器干燥气流速8 mL·min-1,干燥气温度:350℃,静电喷雾电压3500 V;质谱扫描质量范围50～1200 m/z。采用全扫描一级质谱和选择离子全扫描二级质谱(MS/MS)2种方式同时测定。结果:硝西泮与各杂质峰均能良好的分离,杂质A、B、C在0.24～30.0μg.mL-1浓度范围内与峰面积成良好的线性关系,回归方程分别为Y=3.411×104X+384.1,Y=2.411×104 X-258.4,Y=8.982×104 X-1.378×103,r均为1.000,最低检测限分别为0.24 ng、0.36 ng、0.24 ng,高、中、低三浓度的平均回收率分别为100.8%,99.4%,101.3%;并对硝西泮的未知降解产物进行结构分析。结论:该方法简便、灵敏、专属性好,硝西泮和3种已知杂质有良好的分离。Objective：To establish an HPLC-MS method for the determination of three impurities in nitrazepam and its tablets.Method：The separation was performed on a Shimadzu VP-ODS（250 mm × 4.6 mm,5 μm） column with 10 mmol·L-1 potassium dihydrogen phosphate solution-acetonitrile（55：45） as mobile phase at the flow rate of 1.0 mL·min-1,diode-array detector wavelength was set at 220 nm;ion trap mass spectrometey,spray capillary voltage 3.5 kV,dry gas N2 8 mL·min-1,dry gas temperature 350 ℃,scan range 50-1200 m/z,Sample was analyzed in two modes：MS and MS/MS full scan modes.Results：A good separation for nitrazepam and three impurities was achieved.The linear ranges of impurities A,B and C from 0.24 μg·mL-1 to 30.0 μg·mL-1.The average recoveries of impurities A,B and C at three levels were 100.8%,99.4% and 101.3%,respectively.Conclusion：The established HPLC method can be used for the determination of impurities in nitrazepam and its tablets.

关 键 词：硝西泮 液相色谱质谱联用 电喷雾离子化 有关物质 片剂 降解产物 

分 类 号：R917[医药卫生—药物分析学]