硫酸吗啡原料药中有关物质检查方法研究  

Detection Method of Related Substances in Morphine Sulfate

作　　者：彭双 张敏娟 陈学艳 魏文芝 PENG Shuang;ZHANG Min-juan;CHEN Xue-yan;WEI Wen-zhi(Qinghai Provincial Drug Inspection and Testing Institute,Xining 810016,China;NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine,Tibetan Medicine,Xining 810016,China;Qinghai Provincial Key Laboratory of Modernization of Traditional Chinese and Tibetan Medicine,Xining 810016,China)

机构地区：[1]青海省药品检验检测院,西宁810016 [2]国家药品监督管理局中药(藏药)质量控制重点实验室,西宁810016 [3]青海省中藏药现代化研究重点实验室,西宁810016

出　　处：《中国药学杂志》2022年第13期1112-1117,共6页Chinese Pharmaceutical Journal

基　　金：国家药品标准提高研究课题资助(2018H011)。

摘　　要：目的 通过对硫酸吗啡原料药的有关物质进行分析,考察现行标准的完善性,探讨存在的问题,为提高产品质量标准提供参考。方法 采用HPLC,选用Symmetry C_(18)(4.6 mm×150 mm,5μm)色谱柱,以1.01 g·L^(-1)庚烷磺酸钠溶液(用50%磷酸调节pH值至2.6)和甲醇为流动相进行梯度洗脱;检测波长为230 nm,流速为1.5 mL·min^(-1),柱温35℃。结果 国内硫酸吗啡原料药中检出的主要杂质有可待因(杂质A)、伪吗啡(杂质B)、10-羟基吗啡(杂质D)、吗啡酮(杂质E)和吗啡氮氧化物(杂质F),溶液稳定性显示其中伪吗啡含量增加明显,表明样品需临用新配。结论 建立方法的专属性、线性等均良好,能用于硫酸吗啡原料药中有关物质的检测。现行标准中缺少有关物质检查项,建议增加。OBJECTIVE To analyze the impurities in morphine sulfate,investigate and discuss the completeness of the current statutory standard and the existing problems,thus to provide reference for improvement of the quality standard and product quality.METHODS HPLC was performed on a Symmetry C_(18)column(4.6 mm×150 mm,5 μm) with a gradient elution system of 1.01 g·L^(-1) sodium heptanesulfonate(pH was adjusted to 2.6 with 50% phosphoric acid)-methanol at a flow rate of 1.5 ml/min,while the column temperature was maintained at 35 ℃,the detection wavelength was set at 230 nm.RESULTS The main impurities inmorphine sulfate were impurity A(codeine),impurity B(2,2′-bimorphine),impurity D(10S-hydroxymorphine),impurity E(morphinone) and impurity F(morphine N-oxide).The stability test of the solution showed that the content of 2,2′-bimorphine increased obviously,which indicated that the solution sample should be prepared just before the test.CONCLUSION The HPLC method has good specificity and linearity,which is suitable for the determination of related substances in morphine sulfate.There is a lack of detection of related substances in the current statutory standard,which is suggested to be added.

关 键 词：硫酸吗啡 有关物质 高效液相色谱法 伪吗啡 吗啡酮 

分 类 号：R917[医药卫生—药物分析学]