Isomer analysis by mass spectrometry in clinical science

Isomeric compounds are present in the human body as well as in drugs and exhibit different physio-logical functions, making their measurement important in clinical science. Isomer measurement is often difficult even when applying chromatographic separation. To accommodate this, affinity-based sample preparation, such as Immunoprecipitation (IP) and molecularly imprinted polymers (MIP), and hy-phenation to mass spectrometry are becoming increasingly important. Moreover, alternative methods including changes in ionization and dissociation energy, ion molecule reactions, and ion mobility mass spectrometry (IMS) have been developed. This is because mass accuracy and resolution are not sufficient to distinguish isomeric compounds. This review compares and discusses recent (mostly 2017-) advances in mass spectrometry-based isomer analysis methods. The recent technical advances in IMS have proven to be very important, especially when applied to large molecule isomer analyses.(c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

Isomeric compounds play important roles in the human body and drugs with different physiological functions, making their measurement crucial in clinical science. However, measuring isomers is often challenging despite chromatographic separation. Affinity-based sample preparation, such as Immunoprecipitation (IP) and molecularly imprinted polymers (MIP), and the coupling with mass spectrometry have become increasingly important. Additionally, alternative methods including changes in ionization and dissociation energy, ion molecule reactions, and ion mobility mass spectrometry (IMS) have been developed due to the insufficient mass accuracy and resolution to distinguish isomeric compounds. This review discusses recent advancements (mostly 2017-) in mass spectrometry-based isomer analysis methods, highlighting the significance of recent technical advances in IMS, particularly for large molecule isomer analyses.