Separation and photostability analysis of retinoic acid isomers and their derivatives based on ion mobility mass spectrometry and theoretical calculations.

in Talanta by Ying Zou, Chaoxian Chi, Fangling Wu, Chuan-Fan Ding

TLDR

  • Researchers develop a rapid and efficient method for analyzing retinoic acid (RA) isomers and their derivatives using ion mobility mass spectrometry and theoretical calculations.

Abstract

Retinoic acid (RA) regulates cell proliferation, differentiation, and apoptosis and exists in three primary isomers: all-trans-RA (ATRA), 9-cis-RA (9cRA), and 13-cis-RA (13cRA). RA derivatives, such as bexarotene (BT) and arotinoid acid (TTNPB), are used to treat cutaneous T-cell lymphoma and induce cellular pluripotency. Due to their distinct biological activities, accurate identification and analysis of these isomers are crucial. This study developed a rapid and efficient method for analyzing RA isomers and their derivatives using ion mobility mass spectrometry (IM-MS) and theoretical calculations. RA isomers and derivatives exhibit overlapping mobilities and cannot be separated by direct IM-MS. By forming ternary complexes with β-cyclodextrin (β-CD) and metal ions, baseline separation was achieved with a peak resolution (R) of up to 3.42. Tandem MS and theoretical calculations revealed distinct differences in interactions, spatial structures, and binding energies, enabling mobility-based separation. Photostability tests showed rapid photoisomerization of 13cRA into 9cRA and ATRA within seconds. Analysis of 13cRA soft capsules from four brands demonstrated good stability, with measured content aligning closely with labeled values. This method offers a new approach for accurate RA isomer analysis, with potential applications in pharmaceuticals and food industries.

Overview

  • The study aims to develop a rapid and efficient method for analyzing retinoic acid (RA) isomers and their derivatives using ion mobility mass spectrometry (IM-MS) and theoretical calculations.
  • The study focuses on identifying and analyzing the three primary isomers of RA: all-trans-RA (ATRA), 9-cis-RA (9cRA), and 13-cis-RA (13cRA), as well as their derivatives.
  • The primary objective of the study is to develop a method that can accurately separate and analyze RA isomers and their derivatives, which have overlapping mobilities and cannot be separated by direct IM-MS.

Comparative Analysis & Findings

  • The study achieves baseline separation of RA isomers and their derivatives by forming ternary complexes with β-cyclodextrin (β-CD) and metal ions, with a peak resolution (R) of up to 3.42.
  • Tandem MS and theoretical calculations reveal distinct differences in interactions, spatial structures, and binding energies between RA isomers and their derivatives, enabling mobility-based separation.
  • Photostability tests show rapid photoisomerization of 13cRA into 9cRA and ATRA within seconds, highlighting the importance of accurate analysis and stability testing.

Implications and Future Directions

  • The method developed in this study offers a new approach for accurate RA isomer analysis, with potential applications in pharmaceuticals and food industries.
  • Future studies can build on this research to explore the implications of RA isomer analysis on drug development, disease diagnosis, and treatment outcomes.
  • Food companies and regulatory agencies can utilize this method to ensure the accurate labeling and quality control of RA-containing products.
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