盐酸羟考酮原料药中元素杂质控制方法研究  

Quality Control Method of Elemental Impurities in the Active Pharmaceutical Ingredients of Oxycodone Hydrochloride

作　　者：田向斌 柯静 王文丽 张晓明 TIAN Xiangbin;KE Jing;WANG Wenli;ZHANG Xiaoming(Gansu Institute for Drug Control,Lanzhou,Gansu,China 730070)

机构地区：[1]甘肃省药品检验研究院,甘肃兰州730070

出　　处：《中国药业》2023年第21期108-112,共5页China Pharmaceuticals

基　　金：甘肃省药品监督管理局药品科研项目[2020GSMPA016,2020GSMPA012]。

摘　　要：目的建立盐酸羟考酮原料药中元素杂质控制方法。方法采用微波消解法对样品进行前处理,以光谱法(石墨炉原子吸收光谱法、原子荧光光谱法)和电感耦合等离子体质谱(ICP-MS)法分别对盐酸羟考酮原料药和合成起始原料蒂巴因中的元素杂质(第一类元素砷、镉、汞、铅)及催化剂中的钯元素进行分析。结果石墨炉原子吸收光谱法测定盐酸羟考酮原料药中元素杂质控制种类铅元素及钯元素,其质量浓度分别在0~20 ng/mL和0~60 ng/mL范围内与吸光度线性关系良好(r=0.9985,0.9999);方法检测限分别为0.0038μg/g和0.0400μg/g,方法定量限分别为0.013μg/g和0.120μg/g;加样回收率分别为97.04%和105.03%。结论盐酸羟考酮原料药元素杂质控制种类选择铅元素和钯元素。控制限度分别为0.5μg/g和10.0μg/g。与ICP-MS法比较,石墨炉原子吸收光谱法测定铅元素线性范围和检测限具有同量级;测定钯元素检测限较高,但远低于控制限度。所建立的石墨炉原子吸收光谱法灵敏度高、简便快捷、可操作性强,适用于盐酸羟考酮原料药中元素杂质的控制。Objective To establish a method for quality control of elemental impurities in the active pharmaceutical ingredients(API)of oxycodone hydrochloride.Methods The sample was pre-treated by the microwave digestion method,the elemental impurities(Class 1:arsenic,cadmium,mercury,and lead elements)in the API of hydroxycodone hydrochloride and the starting API of tibaine for synthesis,and palladium elements in the catalyst were analyzed by the spectroscopy[graphite furnace atomic absorption spectroscopy(GF-AAS)and atomic fluorescence spectroscopy]and inductively coupled plasma-mass spectrometry(ICP-MS),respectively.Results GF-AAS was used to determine the impurity control types of lead and palladium in the API of hydroxycodone hydrochloride.The linear ranges of lead and palladium were 0-20 ng/mL and 0-60 ng/mL(r=0.9985,0.9999),respectively.The limits of detection(LOD)of the methods were 0.0038μg/g and 0.0400μg/g,and the limits of quantification(LOQ)of the methods were 0.013μg/g and 0.120μg/g,respectively.The recovery rates of lead and palladium were 97.04%and 105.03%,respectively.Conclusion The type of impurity control for the API of hydroxycodone hydrochloride is selected as lead and palladium elements.The control limits are 0.5μg/g and 10.0μg/g,respectively.Compared with ICP-MS method,graphite furnace atomic absorption spectroscopy has the same level of linearity and LOD for the determination of lead element.The LOD for palladium is relatively high,but far below the control limit.The established GF-AAS has high sensitivity,convenience,and strong operability,which is suitable for the quality control of elemental impurities in the API of hydroxycodone hydrochloride.

关 键 词：盐酸羟考酮 铅 钯 石墨炉原子吸收光谱法 电感耦合等离子体质谱法 微波消解 元素杂质 原料药 

分 类 号：R917[医药卫生—药物分析学] R971.1[医药卫生—药学]