# Development of a Robust Platform for Infrared Ion Spectroscopy: A New Addition to the Analytical Toolkit for Enhanced Metabolite Structure Elucidation

## TL;DR

This paper introduces a new infrared ion spectroscopy platform that improves metabolite structure analysis in drug development.

## Contribution

A robust, compact IRIS platform is developed for reliable and efficient metabolite structure elucidation without recalibration.

## Key findings

- The IRIS platform produced highly reproducible spectra over one year without recalibration.
- IRIS successfully identified glucuronidation and oxidation sites in drug molecules.
- The platform's high laser power and repetition rate enabled resolution of all spectral features.

## Abstract

Metabolite identification is essential in drug metabolism
and pharmacokinetics
(DMPK) studies and plays a pivotal role throughout the drug development
process, from informing drug design to evaluating safety and efficacy.
Mass spectrometry (MS) is the analytical technique of choice for characterizing
metabolites due to its selectivity and sensitivity, particularly when
paired with chromatographic methods. However, MS encounters challenges
in structural characterization. This study employs infrared ion spectroscopy
(IRIS) to differentiate isomeric compounds and demonstrates the robustness
of a newly developed IRIS platform. We showcase applications in metabolite
identification by determining the site of glucuronidation and phase
I oxidation in selected drug molecules. Employing density functional
theory for spectral prediction, IRIS decreases reliance on reference
standards and alleviates the time-consuming purification processes
typically associated with metabolite analysis. The newly developed
platform integrates a high-power, high-repetition-rate infrared laser
and ion trap MS. This setup is very robust, as evidenced by the highly
reproducible IRIS spectra recorded over a one-year period without
any instrument readjustment or recalibration. Moreover, the high power
and high repetition rate of the laser provide a large dynamic range
that is necessary to resolve all spectral features. These results
leverage IRIS toward a transformative tool in analytical chemistry,
with potential applications expanding across various fields, such
as impurity analysis and forensics. The introduction of a compact
IRIS setup in an industrial setting not only confirms its practical
applicability but also emphasizes its potential for integration into
routine analytical workflows.