Globally Optimized Targeted Mass Spectrometry: Reliable Metabolomics Analysis with Broad Coverage

Area of Science:

• Metabolomics
• Mass Spectrometry
• Biochemistry

Background:

• Targeted detection in mass spectrometry (MS)-based metabolomics offers limited coverage due to small metabolite sets.
• Global profiling provides broad coverage but may lack quantitation accuracy and sensitivity for specific targets.

Purpose of the Study:

• To introduce Globally Optimized Targeted (GOT)-MS, a novel approach integrating targeted and global metabolomics.
• To enhance metabolite coverage, quantitation, and the ability to detect unknown metabolites in MS-based analyses.

Main Methods:

• Developed GOT-MS using a single liquid chromatography-triple quadrupole (LC-QQQ) mass spectrometer.
• Executed a global search of precursor and product ions, acquiring 595 precursor ions and 1,890 multiple reaction monitoring (MRM) transitions.
• Analyzed serum metabolites under positive and negative ionization modes within the 60-600 Da mass range.

Main Results:

• GOT-MS demonstrated analytical performance comparable or superior to global profiling with quadrupole-time-of-flight (Q-TOF) instruments.
• In a colorectal cancer (CRC) study, GOT-MS significantly outperformed a targeted MS assay of ~160 metabolites.
• GOT-MS provided complementary data to traditional Q-TOF-MS global profiling.

Conclusions:

• GOT-MS expands and optimizes detection capabilities for triple quadrupole (QQQ)-MS instruments.
• This approach offers broad metabolite coverage, unknown detection, and excellent quantitation.
• GOT-MS holds significant potential for advancing both basic and clinical metabolic research.