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-C18色谱柱(2.1 mm×100 mm,2.7 μm),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=0.999 9);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=0.999 6);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、2.09 μg·g-1和0.19、0.34、0.24、0.16 μg·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-C18 column(2.1 mm×100 mm, 2.7 μm),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 and 0.27 ng·mL-1; the linear ranges were 0.3-10.8 ng·mL-1(r=0.999 9) and 0.3-10.8 ng·mL-1(r=0.999 6); 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, 2.09 μg·g-1 and 0.19, 0.34, 0.24, 0.16 μg·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.
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