Objective:

To explore the application of comprehensive two-dimensional gas chromatography (GC×GC) in revealing chemical information obscured by conventional separations.

Approach:

• Biomarker Discovery: Utilized GC×GC to identify crotonylglycine as a novel urinary biomarker for HMGCS2 deficiency, previously obscured in one-dimensional GC-MS.
• Aviation Fuel Analysis: Investigated trace oxidation products in high-performance aviation fuel to distinguish them from a complex hydrocarbon matrix.
• Shape-Shifting Molecules: Examined molecules that interconvert during chromatographic separation, leading to unresolved compositions in one-dimensional GC.

Key Findings:

• Crotonylglycine was identified as a novel urinary biomarker for HMGCS2 deficiency using GC×GC-TOFMS.
• Conventional one-dimensional GC-MS failed to detect crotonylglycine due to coelution with adipic acid.
• The urinary organic acid profile can be transient, complicating the identification of metabolic disorders.

Interpretation:

The findings illustrate how advances in chromatographic techniques can enhance the detection of biomarkers and improve diagnostic capabilities for inborn errors of metabolism.

Limitations:

• The urinary organic acid profile may not always reflect metabolic disorders outside of acute presentations.
• False-negative results can occur if samples are collected during periods of metabolic stability.

Conclusion:

GC×GC has expanded the repertoire of detectable biomarkers, enhancing the diagnosis of metabolic disorders.