色谱-质谱法同时测定泮托拉唑钠中3种基因毒性杂质  

Simultaneous Determination of 3 Genotoxic Impurities in Pantoprazole Sodium by Chromatography-Mass Spectrometry

作　　者：徐秀卉[1] 陈玲芳[1] 楼明波 XU Xiuhui;CHEN Lingfang;LOU Mingbo(Hangzhou Conba Pharmaceutical Co.,Ltd.,Hangzhou 310052,China;Zhejiang Conba Pharmaceutical Co.,Ltd.,Hangzhou 310052,China)

机构地区：[1]杭州康恩贝制药有限公司,杭州310052 [2]浙江康恩贝制药股份有限公司,杭州310052

出　　处：《中国现代应用药学》2024年第10期1381-1387,共7页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的建立一种色谱-质谱法检测泮托拉唑钠中的3种基因毒性杂质。方法采用色谱-质谱法,色谱柱为十八烷基硅烷键合硅胶为填充剂[Kromasil 100-5(4.6 mm×25 cm,5μm)或效能相当的色谱柱],以乙腈-0.01 mol·L^(-1)乙酸铵(35∶65)为流动相,流速0.9 mL·min^(-1),柱温25℃;正离子检测模式,扫描范围:150~450 Da,干燥器温度350℃,干燥气流速10 L·min^(-1),雾化气压力50 psig,毛细管电压4000 V,碎裂电压175 V,锥孔电压65 V。切入质谱的时间设为0~3.5 min弃去(进入废液),3.5 min~主峰保留时间-0.5 min进入质谱检测器,主峰保留时间-0.5 min~结束再弃去(进入废液)。结果基因毒性杂质1浓度在9.04~27.13 ng·mL^(-1)内与峰面积线性关系良好(r=0.998),基因毒性杂质2浓度在8.92~26.75 ng·mL^(-1)内与峰面积线性关系良好(r=0.999),中间体Ⅱ浓度在7.78~23.34 ng·mL^(-1)内与峰面积线性关系良好(r=0.990);基因毒性杂质1的定量限为9.0430 ng·mL^(-1),检测限为0.9043 ng·mL^(-1);基因毒性杂质2的定量限为8.9174 ng·mL^(-1),检测限为2.9725 ng·mL^(-1);中间体Ⅱ的定量限为7.7792 ng·mL^(-1),检测限为0.7779 ng·mL^(-1);3种基因毒性杂质的各浓度回收率在92.3%~107.0%,RSD为2.0%~7.9%。经检测泮托拉唑钠中均未检出3种杂质。结论该方法能对泮托拉唑钠原料基因毒性杂质1、基因毒性杂质2、中间体Ⅱ3种基因毒性杂质进行准确的定量测定,方法专属性强、灵敏度高、实验操作简便、快速,可用于泮托拉唑钠中以上3种基因毒性杂质的测定。OBJECTIVE To establish a chromatography-mass spectrometry method for simultanenous detection of 3 genotoxic impurities in pantoprazole sodium.METHODS The chromatographic column was octadecylsilane bonded silica gel as filler(Kromasil 100-5,4.6 mm×25 cm,5μm or equivalent column),acetonitrile-0.01 mol·L^(-1)ammonium acetate(35∶65)as mobile phase,flow rate 0.9 mL·min^(-1),column temperature 25℃;positiveion detection mode,scanning range:150-450 Da,dryer temperature 350℃,dry gas flow rate 10 L·min^(-1),atomization gas pressure 50 psig,capillary voltage 4000 V,fragmentation voltage 175 V,cone hole voltage 65 V.The time for entering the mass spectrometry was set to 0-3.5 minutes to waste,3.5 minutes to retain the main peak-0.5 minutes to MS,and 0.5 minutes to end to waste.RESULTS The concentration of genotoxic impurity 1 had a good linear relationship with peak area between 9.04-27.13 ng·mL^(-1)(r=0.998),the concentration of genotoxic impurity 2 had a good linear relationship with peak area between 8.92-26.75 ng·mL^(-1)(r=0.999),and the concentration of intermediate II had a good linear relationship with peak area between 7.78-23.34 ng·mL^(-1)(r=0.990);the quantitative limit of genotoxic impurity 1 was 9.0430 ng·mL^(-1),and the detection limit was 0.9043 ng·mL^(-1);the quantitative limit of genotoxic impurity 2 was 8.9174 ng·mL^(-1),and the detection limit was 2.9725 ng·mL^(-1);the quantitative limit of intermediate II was 7.7792 ng·mL^(-1),and the detection limit was 0.7779 ng·mL^(-1);the recovery rate of 3 genotoxic impurities ranges from 92.3%-107.0%,with an RSD of 2.0%-7.9%.No three impurities were detected in pantoprazole sodium.CONCLUSION This method can accurately and quantitatively determine three genotoxic impurities of pantoprazole sodium raw material:genotoxic impurity 1,genotoxic impurity 2,and intermediate II.The method has strong specificity,high sensitivity,simple and rapid experimental operation,and can be used for the determination of the above three genotoxic impurities in pantopraz

关 键 词：泮托拉唑钠 基因毒性杂质 色谱-质谱法 

分 类 号：R917.101[医药卫生—药物分析学]