摘要
目的:建立液相质谱联用方法精确测定左旋泮托拉唑钠中2个基因毒杂质氮氧化物和亚砜氮氧化物的含量。方法:采用Agilent Infinity Lab Poroshell 120 EC-C_(18)色谱柱(2.1 mm×100 mm,2.7μm),以10 mmol·L^(-1)乙酸铵溶液(含0.05%甲酸)为流动相A,乙腈为流动相B,梯度洗脱。ESI源正离子模式下,采用MRM离子检测模式,氮氧化物杂质和亚砜氮氧化物杂质监测的离子对分别为m/z 400.0/216.1和m/z 415.9/232.2。结果:氮氧化物杂质的检测下限为0.12 ng·mL^(-1),定量下限为0.31 ng·mL^(-1),在0.3~10.8 ng·mL^(-1)内线性关系良好(r=0.9999);亚砜氮氧化物杂质的检测下限为0.05 ng·mL^(-1),定量下限为0.27 ng·mL^(-1),在0.3~10.8 ng·mL^(-1)浓度内线性关系良好(r=0.9996);氮氧化物杂质、亚砜氮氧化物杂质加样回收率的平均值分别为100.9%和100.1%,RSD分别为3.1%和3.5%。4批样品中2个基因毒杂质的含量分别为2.31、1.99、2.30、2.09μg·g^(-1)和0.19、0.34、0.24、0.16μg·g^(-1)。结论:经方法学验证,本方法简便,准确可靠,能够同时测定左旋泮托拉唑钠中2个基因毒性杂质含量。
Objective:To establish a method for simultaneous determination of impurity sulfiny dimethoxypyridine 1-oxide(sulfiny N-oxide)and sulfony dimethoxypyridine 1-oxide(sulfony N-oxide),known as potential genotoxic impurities in S-pantoprazole sodium by LC-MS/MS.Methods:The separation was performed on an Agilent Infinity Lab Poroshell 120 EC-C_(18)column(2.1 mm×100 mm,2.7μm),with mobile phase consisted of 10 mmol·L^(-1)ammonium acetate containing 0.05%formic acid(A)and acetonitrile(B)by gradient elution,at a flow rate of 0.4 mL·min^(-1);the detection was accomplished by ESI in the positive mode using multiple-reaction monitoring.The optimized mass ion-pairs for quantitation were m/z 400.0/216.1 and m/z 415.9/232.2 for impurity sulfiny N-oxide and sulfony N-oxide,respectively.Results:For impurity sulfiny N-oxide and sulfony N-oxide,the LODs were 0.12 and 0.05 ng·mL^(-1),respectively;the LOQs were 0.31 and0.27 ng·mL^(-1);the linear ranges were 0.3-10.8 ng·mL^(-1)(r=0.9999)and 0.3-10.8 ng·mL^(-1)(r=0.9996);the average recoveries were 100.9%(RSD=3.1%,n=9)and 100.1%(RSD=3.5%,n=9).The results of impurity sulfiny N-oxide and sulfony N-oxide in 4 patches sample were 2.31,1.99,2.30,2.09μg·g^(-1)and 0.19,0.34,0.24,0.16μg·g^(-1),respectively.Conclusion:The method is accurate,rapid,sensitive,selective and suitable for the content determination of 2 genotoxic impurities in S-pantoprazole sodium.
作者
朱玲
胡楚红
朱叶芬
汤谷平
ZHU ling;HU Chu-hong;ZHU Ye-fen;TANG Gu-ping;无(School of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310000,China;East China Pharmaceutical Group New Grug Institute Limited Co.,Ltd.,Hangzhou 310000,China;Institute of Organic and Medicinal Chemistry,Zhejiang University,Hangzhou 310000,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2021年第12期2115-2121,共7页
Chinese Journal of Pharmaceutical Analysis
关键词
左旋泮托拉唑钠
液相质谱联用
氮氧化物
亚砜氮氧化物
基因毒杂质
含量
S-pantoprazole
LC-MS/MS
sulfiny dimethoxypyridine oxide
sulfony dimethoxypyridine oxide
genotoxic impurities
assay
