Simultaneous Determination of 3 Genotoxic Impurities in Pantoprazole Sodium by Chromatography-Mass Spectrometry
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,5 μm 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 4 000 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 9.043 0 ng·mL-1,and the detection limit was 0.904 3 ng·mL-1;the quantitative limit of genotoxic impurity 2 was 8.917 4 ng·mL-1,and the detection limit was 2.972 5 ng·mL-1;the quantitative limit of intermediate Ⅱ was 7.779 2 ng·mL-1,and the detection limit was 0.777 9 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 pantoprazole sodium.
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