Simultaneous determination of three genotoxic impurities in aripiprazole by two-dimensional column switching high performance liquid chromatography
Zhou Lin
Wu Tao
Lou Yong-ming
Abstract：Objective To establish a method of column switching high-performance liquid chromatography for the determi-nation of three genotoxic impurities in aripiprazole. Methods For preliminary separation,an Agilent ZORBAX SB-C18 column (4.6 mm×150 mm,5 μm) was used as one-dimensional chromatographic column,and acetonitrile-0.05％ trifluoroacetic acid (40:60) was set as mobile phase. The flow rate was 1.0 mL·min-1and the injection volume was 50 μL. The detection wavelength was set at 254 nm with column temperature at 40℃. The switching time was from 12 to 18 minutes. For impurity analysis,two-dimension-al chromatographic separation was conducted on an Agilent Eclipse XDB-C8 column (4.6 mm×150 mm,5 μm),and other chro-matographic conditions were the same with one-dimensional chromatography. Results The impurities 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone(PPA-A),6-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone(PPA-ZP) and 5-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone(PPA-ZQ) showed favorable linear relationship in the range of 0.1035～0.5175 μg·mL-1 (r=0.9997),0.1023～0.5115 μg·mL-1 (r=0.9990) and 0.1066～0.5330 μg·mL-1 (r=0.9998) respectively. Both the RSD of repeatability and stabil-ity were less than 3.6％. The average recoveries were 98.9％～103.4％ with RSD not more than 3.5％. The limit of quantification was 0.1 μg·mL-1 and that of detection was 0.04 μg·mL-1. Conclusion This method shows strong specificity,which can be used to ef-fectively separate impurities,improve baseline noise,enhance detection sensitivity and reduce economic costs. Therefore,it provides a new technical support for the clinical safety and quality control of aripiprazole.
Keywords：AripiprazoleColumn switchingGenotoxic impuritiesHigh performance liquid chromatographyQuality control
Publication Date：2024-12-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 867-870 )