Novel Method for Simultaneously Untargeted Metabolome and Targeted Exposome Analysis in One Injection

Area of Science:

• Analytical Chemistry
• Biochemistry
• Environmental Health

Background:

• Metabolomics and exposomics are crucial for understanding human health.
• Current metabolome-exposome-wide association studies (mEWAS) require separate analyses, increasing time and sample needs.
• High-resolution mass spectrometry (HRMS) and triple quadrupole tandem mass spectrometry are commonly used, but have limitations for combined analyses.

Purpose of the Study:

• To develop a novel, unified method for simultaneous untargeted metabolome and targeted exposome analysis in a single injection.
• To leverage Zeno MRM^HR technology for enhanced sensitivity and efficiency in mEWAS.
• To validate the method's performance for both endogenous metabolites and exogenous compounds.

Main Methods:

• Utilized Zeno MRM^HR technology for simultaneous high-resolution mass spectrometry (HRMS) and multiple reaction monitoring (MRM) acquisition.
• Validated the method using exogenous standards, assessing intraday and interday repeatability (RSD < 20%).
• Analyzed over 90% of metabolic features with RSD < 20% and determined broad quantification ranges (LLOQ: 0.1–25 ng/mL, HLOQ: 2.5–1000 ng/mL).

Main Results:

• Achieved comparable signal responses for exogenous compounds in MRM mode to metabolites in HRMS mode.
• Demonstrated high repeatability and a wide quantification range for the unified method.
• Successfully applied the method to a type 2 diabetes mellitus cohort to identify serum risk factors and metabolome-exposome associations.

Conclusions:

• The developed unified method enables simultaneous untargeted metabolome and targeted exposome analysis in a single injection.
• This novel approach offers a significant advancement for mEWAS research, reducing resource requirements.
• The method provides a powerful new tool for investigating the complex interplay between metabolites and exposures in human health.