Purity Assessment Of Reference Materials Based On Liquid Chromatography-Corona Charged Aerosol Detection Technology

In organic purity assessment,chromatography separation with a suitable detector is required.Diode array detection(DAD)has been a widely used technique for high-performance liquid chromatography(HPLC)analyses,but its application is limited to compounds with sufficient UV chromophores.Charged aerosol detector(CAD),as a mass-dependent detector,is advantageous for providing a nearly uniform response for analytes,regardless of their structures.Dulcitol is a natural product extracted from plants.It is a non-volatile compound with no UV absorption and cannot be determined by UV detector.Therefore,liquid chromatography-electrospray detector(HPLC-CAD)was applied to determine the purity of dulcitol,which can also provide a complementary technique for the detection of other compounds without UV absorption.In this study,based on the principle of CAD,the response uniformity was analyzed,and 11 non-volatile compounds with/without UV chromophores were directly and continuously injected in non-column mode.The RSDs of CAD responses were within 17%.Especially analogues were more consistent(2.12%for carbohydrates and 8.14% for bisphenols).In addition,the correlation analysis between the response results and the properties of the compound showed that the density of the compound was negatively correlated with the response,but the density difference of similar compounds was small,and the CAD response was more consistent(RSDs < 10%).Due to the presence of ultraviolet chromophore of bisphenol,HPLC-CAD showed a more uniform response compared with HPLC-DAD.Therefore,HPLC-CAD method could be used to determine related structure impurities(RSIs)in dulcitol.The chromatographic conditions and CAD parameters of the method were optimized.The linear correlation,repeatability,and sensitivity of the method were evaluated,and the method was applied to the development of reference materials for dulcitol.According to the standard requirement,the qualitative analysis and purity determination of dulcitol were carried out.Moreover,infrared absorption spectrometry,high resolution mass spectrometry,and nuclear magnetic resonance were used for qualitative analysis.HPLC-CAD was used to evaluate the homogeneity and stability of dulcitol.The results showed that the homogeneity and stability were satisfactory,and the introduced uncertainties were 0.009% and0.012%,respectively.The purity of dulcitol determined by the mass balance method and differential scanning calorimetry(DSC)method were 99.84% and99.85%,and the uncertainty was 0.15% and 0.09%,respectively.Finally,the purity of dulcitol was synthetic,and the results was 99.8% with 0.1% uncertainty.