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Comprehensive Two-Dimensional Gas Chromatography/Time-of-Flight Mass Spectrometry (GC x GC/TOF-MS)


Although conventional gas chromatography mass spectrometry (GC/MS) provides relatively high efficiency separations, the analysis of some complex, natural-matrix samples may require the use of even higher resolution approaches. Comprehensive two-dimensional gas chromatography (GC x GC) is an emerging high-resolution technology which uses coupled GC columns to achieve separations that are not possible by conventional GC. Separations in the “first dimension” that are carried out on a long GC column are directed via a modulator to a short GC column with different selectivity (the “second dimension”), and are detected by time of flight mass spectrometry (TOF-MS). Because the entire sample is represented in the analysis, the technique is described as “comprehensive.” Efforts at NIST are being directed toward the study of issues related to quantitation by GC x GC/TOF-MS, and to the value assignment of complex matrix Standard Reference Materials. A particular emphasis is being placed on metabolomics and environmental applications.


The development of robust analytical methods remains one of the most important (and costly) parts of chemical metrology. The resolution of targeted constituents is requisite for accurate and precise measurements. High-resolution separation technologies provide several advances over conventional approaches: (1) increased capabilities for the analysis of complex samples; (2) easier and less costly method development; (3) more robust methods that remain in control even if changes over time result in de-optimization; (4) more accurate and precise metrology. The Analytical Chemistry Division has a variety of measurement efforts that involve the analysis of complex matrix samples. GC x GC/TOF-MS will provide high-resolution separations that will be used for both qualitative and quantitative analysis.

Additional Technical Details:

GC columns are being strategically chosen for use in the first and second dimensions to assess the separation capabilities of the GC x GC technique for metabolomics research and environmental applications. Three initial applications are being studied: (1) determination of amino acids (with different derivatization methods), (2) determination of cholesterol (using a traditional derivitization method), and (3) determination of PAHs. 

Major Accomplishments:

  • The qualitative assessment of SRM 1950 is on-going, using different extraction and derivitization methods. Thus far 100 potential metabolites have been identified by mass spectral and retention indices matching, including 18 organic acids, 24 fatty acids and 31 amino acids.  Twenty-five amino acids have been confirmed by comparison with reference standards.
  • Cholesterol has been quantified in SRM 1950 using GC x GC/TOF-MS, and the concentration agrees well with the concentration determined using a “definitive method.”
  • The quantification of the amino acids in SRM 1950 is ongoing. Data derived from GC x GC/TOF-MS is being compared with LC/MS data.