HPLC-CAD as a supplementary method for the quantification of related structure impurities for the purity assessment of organic CRMs

Anal Bioanal Chem. 2023 Jul;415(17):3375-3384. doi: 10.1007/s00216-023-04719-2. Epub 2023 May 8.

Abstract

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. In this study, 11 non-volatile compounds with/without UV chromophores were analyzed by CAD using continuous direct injection mode. The RSDs of CAD responses were within 17%. For saccharides and bisphenols, especially, the RSDs were lower (2.12% and 8.14%, respectively). Since bisphenols exist in UV chromophores, their HPLC-DAD responses were studied and compared with CAD responses, with CAD showing a more uniform response. Besides, the key parameters of HPLC-CAD were optimized and the developed method was verified using a Certified Reference Material (CRM, dulcitol, GBW06144). The area normalization result of dulcitol measured by HPLC-CAD was 99.89% ± 0.02% (n = 6), consistent with the certified value of 99.8% ± 0.2% (k = 2). The result of this work indicated that the HPLC-CAD method could be a good complementary tool to traditional techniques for the purity assessment of organic compounds, especially for compounds lacking UV chromophores.

Keywords: Charged aerosol detector; Purity assessment; Related structure impurity; Response uniformity.

MeSH terms

  • Aerosols / analysis
  • Benzhydryl Compounds* / analysis
  • Chromatography, High Pressure Liquid / methods
  • Phenols* / analysis

Substances

  • Phenols
  • Aerosols
  • Benzhydryl Compounds