超高效液相色谱法测定硫酸吗啡及硫酸吗啡缓释片的有关物质  

Determination of the Impurities in Morphine Sulfate and Morphine Sulfate Sustained-release Tablets by Ultra High Performance Liquid Chromatography

作　　者：刘海涛 寇晋萍 侯金凤 刘琦 车宝泉 Liu Haitao;Kou Jinping;Hou Jinfeng;Liu Qi;Che Baoquan(Beijing Institute for Drug Control,NMPA Key Laboratory for Research and Evaluation of Generic Drugs,Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine,Beijing 102206,China)

机构地区：[1]北京市药品检验研究院,国家药品监督管理局仿制药研究与评价重点实验室,中药成分分析与生物评价北京市重点实验室,北京102206

出　　处：《中国药事》2024年第7期807-820,共14页Chinese Pharmaceutical Affairs

摘　　要：目的:建立硫酸吗啡及其制剂杂质谱分析的超高效液相色谱法(UHPLC法)。方法:使用ACQUITY UPLC HSS C_(18)(100 mm×2.1 mm,1.8μm)色谱柱,以0.101%庚烷磺酸钠溶液(用50%磷酸溶液调节pH至2.6)和甲醇为流动相,梯度洗脱,柱温35℃,流速0.3 mL·min^(-1),检测波长230 nm。结果:本方法可实现磷酸可待因(杂质A)、伪吗啡(杂质B)、东罂粟碱(杂质C)、10-羟基吗啡(杂质D)、吗啡酮(杂质E)、吗啡氮氧化物(杂质F)和14-羟基吗啡酮(杂质G,基因毒性杂质)之间及其他相邻杂质之间的良好分离,UHPLC的使用,大大减少了分析时间和有机溶剂甲醇的消耗量,更为绿色环保。结论:该方法首次将硫酸吗啡各已知杂质和14-羟基吗啡酮在UHPLC条件下同时分离,专属性良好,并用校正因子法对原料药和制剂中的7个已知杂质进行准确定量,且可同时测定硫酸吗啡原料药及其制剂硫酸吗啡缓释片中的有关物质,为原料药的选择和制剂工艺的控制提供技术依据。Objective:To Establish an Ultra High Performance Liquid Chromatography(UHPLC)method to determine impurities in morphine sulfate and morphine sulfate sustained-release tablets.Methods:ACQUITY UPLC HSS C_(18)(100 mm×2.1 mm,1.8μm)chromatographic column was used to determine,with 0.101%sodium heptane sulfonate solution(adjusted to pH 2.6 with 50%phosphoric acid solution)and methanol as the mobile phase for gradient elution,column temperature at 35℃,flow rate of 0.3 mL·min^(-1),and detection wavelength of 230 nm.Results:This method achieved good separation between codeine phosphate(impurity A),pseudomorphine(impurity B),oripavine(impurity C),10-hydroxymorphine(impurity D),morphine ketone(impurity E),morphine nitrogen oxide(impurity F),and 14-hydroxymorphine ketone(impurity G,genotoxic impurity),as well as other adjacent impurities.The use of UHPLC greatly reduced analysis time and the consumption of organic solvent methanol,making it more green and environmentally friendly.Conclusion:This method is the first to simultaneously separate all known impurities of morphine sulfate and 14-hydroxymorphone ketone under UHPLC conditions with good specificity,and the correction factor method is used to accurately quantify the 7 known impurities in the API and the preparation,and the related substances in morphine sulfate and its preparation morphine sulfate sustained-release tablets can be determined at the same time,which provides a technical basis for the selection of raw materials and the control of the preparation process.

关 键 词：硫酸吗啡 硫酸吗啡缓释片 超高效液相色谱法 基因毒性杂质 

分 类 号：R917[医药卫生—药物分析学]