摘要
目的建立测定枸橼酸芬太尼注射液中有关物质含量的高效液相色谱(HPLC)法。方法色谱柱为Shim-packscepter C_(18)-120柱(150 mm×4.6 mm,5μm),流动相为0.01 mol/L氯化铵溶液-乙腈(950∶50,V/V)-0.01 mol/L氯化铵溶液-乙腈(400∶600,V/V),梯度洗脱,流速为1.0 mL/min,检测波长为210 nm,柱温为40℃,进样量为100μL。结果杂质Ⅰ、杂质Ⅱ、杂质Ⅲ、杂质Ⅺ的质量浓度分别在0.02~0.50μg/mL、0.02~0.50μg/mL、0.02~0.49μg/mL、0.02~0.50μg/mL范围内与峰面积线性关系良好(r>0.993);检测限分别为1.00,1.00,0.98,1.00 ng,定量限分别为2.01,2.00,1.97,2.01 ng;重复性试验结果各杂质的RSD均小于2.0%(n=6);中间精密度试验结果各杂质的RSD均小于3.0%(n=12);平均加样回收率分别为98.03%,100.04%,97.94%,101.03%,RSD分别为1.61%,1.09%,0.98%,1.36%(n=9);2种规格(各3批)的中试样品中各特定杂质及未知杂质的含量均小于0.05%(忽略限)。结论该方法操作简便,专属性强,灵敏度、耐用性好,准确度、精密度较高,各杂质分离度优于《中国药典》《英国药典》中的方法,可用于枸橼酸芬太尼注射液中有关物质的含量测定。拟订样品中含杂质Ⅰ、杂质Ⅱ和杂质Ⅺ不得过标示量的0.5%,最大未知杂质不得过0.2%,总未知杂质不得过0.75%。
Objective To establish a high-performance liquid chromatography(HPLC)method for the content determination of related substances in Fentanyl Citrate Injection.Methods The chromatographic column was Shim-pack scepter C_(18)-120 column(150 mm×4.6 mm,5μm),the mobile phase was 0.01 mol/L ammonium chloride solution-acetonitrile(950∶50,V/V)-0.01 mol/L ammonium chloride solution-acetonitrile(400∶600,V/V)with gradient elution,the flow rate was 1.0 mL/min,the detection wavelength was 210 nm,the column temperature was 40℃,and the injection volume was 100μL.Results The linear ranges of impurityⅠ,impurityⅡ,impurityⅢand impurityⅪwere 0.02-0.50μg/mL,0.02-0.50μg/mL,0.02-0.49μg/mL,and 0.02-0.50μg/mL(r>0.993),respectively.The limits of detection(LOD)were 1.00,1.00,0.98,and 1.00 ng,respectively.The limits of quantitation(LOQ)were 2.01,2.00,1.97,and 2.01 ng,respectively.The RSD of each impurity in the repeatability test was lower than 2.0%(n=6).The RSD of each impurity in the intermediate precision test was lower than 3.0%(n=12).The average recoveries of impurityⅠ,impurityⅡ,impurityⅢand impurityⅪwere 98.03%,100.04%,97.94%,and 101.03%,with RSDs of 1.61%,1.09%,0.98%,and 1.36%(n=9),respectively.The content of specific and unknown impurities in the pilot samples of two specifications(three batches each)was lower than 0.05%(disregard limit).Conclusion The method is simple,specific,and sensitive,with good durability,high accuracy and precision,the separation of various impurities in this method is superior to the methods in the Chinese Pharmacopoeia and the British Pharmacopoeia,it is suitable for the determination of related substances in Fentanyl Citrate Injection.The impurityⅠ,impurityⅡ,impurityⅢ,and impurityⅪin the samples shall not exceed 0.5%of the labeled amount,the maximum unknown impurities shall not exceed 0.2%,and the total unknown impurities shall not exceed 0.75%.
作者
宋文涛
曾令高
高梓真
王佳瑜
冯旭
许向阳
SONG Wentao;ZENG Linggao;GAO Zizhen;WANG Jiayu;FENG Xu;XU Xiangyang(Pharmaceutical Research Institute of Jiangsu Nhwa Pharmaceutical Co.,Ltd.·Jiangsu Provincial Key Laboratory of Central Nervous Systerm Drugs,Xuzhou,Jiangsu,China 221000;Chongqing Institute for Food and Drug Control·NMPA Key Laboratory for Quality Monitoring of Narcotic Drugs and Psychotropic Substances,Chongqing,China 401121)
出处
《中国药业》
2024年第3期15-19,共5页
China Pharmaceuticals
基金
重庆英才计划“包干制”项目[cstc2021ycjh-bgzxm0315]。
作者简介
第一作者:宋文涛,男,硕士,执业药师,中级工程师,研究方向为药物分析,(电子信箱)502357418@qq.com。江苏省中枢神经药物研究重点实验室项目骨干,从事药物分析和药品质量标准的建立、优化与提升等工作。作为主要人员参与并完成麻醉类仿制药开发项目3项,普通口服固体制剂开发项目2项,普通注射剂开发项目2项;通信作者:许向阳,男,博士,研究员,研究方向为中枢神经系统药物,(电子信箱)xuxiangyang@nhwa-group.com。
