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The Analytical Scientist / Issues / 2026 / October / GC×GC Detective Stories: Biomarkers, Biofuels, and Shape-Shifting Molecules
Chromatography Environmental Pharma and Biopharma Gas Chromatography Petrochem

GC×GC Detective Stories: Biomarkers, Biofuels, and Shape-Shifting Molecules

Philip Marriott, Renée Webster, and Konstantinos Kouremenos revisit three investigations in which an additional dimension of separation provided the information needed to solve three very different analytical mysteries

By James Strachan, Frank van Geel 10/01/2026 11 min read
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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.

This content is an AI-generated, fully rewritten summary based on a published scholarly article. It does not reproduce the original text and is not a substitute for the original publication. Readers are encouraged to consult the source for full context, data, and methodology.

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About the Author(s)

James Strachan

Over the course of my Biomedical Sciences degree it dawned on me that my goal of becoming a scientist didn’t quite mesh with my lack of affinity for lab work. Thinking on my decision to pursue biology rather than English at age 15 – despite an aptitude for the latter – I realized that science writing was a way to combine what I loved with what I was good at. From there I set out to gather as much freelancing experience as I could, spending 2 years developing scientific content for International Innovation, before completing an MSc in Science Communication. After gaining invaluable experience in supporting the communications efforts of CERN and IN-PART, I joined Texere – where I am focused on producing consistently engaging, cutting-edge and innovative content for our specialist audiences around the world.

More Articles by James Strachan

Frank van Geel

Frank van Geel is owner of educational website Chromedia and Scientific Director of The Analytical Scientist. He studied analytical chemistry, specialized in mass spectrometry in the Netherlands and did several years of post-doc work in spectroscopy with Jim Winefordner at the University of Florida in the US. Then he became a science teacher and later publisher in chemistry and physics related topics. He developed numerous publications in chemistry and other sciences. He strongly supports the mission: Building online communities is the road to take. We need to strengthen the quality of analytical chemistry and we need to strengthen our community by sharing know-how and by sharing our opinions, visions and our views of the future of analytical science.

More Articles by Frank van Geel

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