Liquid chromatography–mass spectrometry (LC-MS) and gas chromatography–mass spectrometry (GC-MS) are two of the most important analytical tools used in modern testing laboratories. Together, they enable professionals to identify and measure trace chemicals in a wide range of materials – from drinking water to pharmaceuticals, food, indoor air, and manufactured products. As a result, these techniques form an analytical foundation for regulatory compliance, product safety, and quality control across nearly every environmental, chemical, and manufacturing industry.
In practice, LC-MS and GC-MS are often used side-by-side to measure different analytes within the same sample matrix. For example, PFAS compounds are typically analyzed using LC-MS methods, which can detect trace levels of the majority of regulated compounds. However, comprehensive PFAS testing packages frequently also include GC-MS to capture certain volatile PFAS compounds that are not well suited to LC-MS. This shows how the choice of technique significantly impacts the types of species that can be analyzed.
Choosing between gas chromatography & liquid chromatography
LC-MS and GC-MS are not competing technologies in the sense that one is better or more advanced than the other. Instead, the choice between them depends on the matrix, targeted analytes, and degree of confidence required.
GC-MS is best suited for analytes that are:
Volatile or semi-volatile
Thermally stable
Low to moderate molecular weight
Non-polar to moderately polar
Able to be vaporized without degradation
Typical examples include:
Volatile organic compounds (VOCs)
Residual solvents
Fragrances and flavor compounds
Fuels and hydrocarbons
On the other hand, LC-MS is best suited for analytes that are:
Non-volatile
Thermally labile
Polar or highly polar
High molecular weight
Present at ultra-trace levels in complex matrices
Typical examples include:
PFAS compounds
Pharmaceuticals and metabolites
Pesticides in food and water
Dyes and pigments
Biomolecules
There can be some exceptions stemming from specific analytical needs or sample preparation procedures. For example, chemical derivatization is commonly used to improve the volatility of analytes for GC-MS measurements.
Choosing a chromatography detector
While GC-MS and LC-MS are very commonly used for compositional analyses, other detectors besides mass spectrometry are also used in conjunction with GC and LC. The detector choice is driven by:
Required sensitivity
Selectivity and identification confidence
Target analyte class
Budget and operational complexity
Regulatory expectations
For many regulatory and environmental applications, detector choice follows the most practical methods to reach the required limits of detection or quantification. This is often using MS, or MS/MS, which both have exceptionally low detection limits in most use cases. However, for routine quality control tests, where the analytes and sample matrices are well-known, simpler detectors are often used. Some examples of these are flame ionization detection (FID), thermal conductivity detection (TCD), and UV detection.
Table 1: Comparison of selected chromatography techniques
Technique | Scope | Resolution | Matrices |
Broad (e.g., chemical screening, reaction products, dyes & pigments) | ppt - ppm | Clean to moderately complex (e.g., clean solvents, reaction mixtures, food extracts) | |
Broad (e.g., PFAS, drugs, pesticides) | < ppt - ppb | Complex (e.g., blood, natural water, biofilms, soil) | |
LC-UV/DAD | Analytes with chromophores (e.g., additives, vitamins, preservatives) | ppb - ppm | Clean to moderately complex (e.g., food, beverages, pharmaceuticals) |
Broad (e.g., VOCs, solvents, fragrances) | ppb - ppm | Clean to moderately complex | |
Polymers (e.g., plastics, rubbers, microplastics) | ppm - % | Polymers, fibers, paints, soils with microplastics, consumer products | |
Organics (e.g., hydrocarbons, solvents, fuels, simple VOCs) | ppb - ppm | Clean gases and liquids | |
GC-TCD | Permanent gases and simple volatiles (e.g., industrial gas, indoor air) | ppm - % | Clean gas mixtures |
The following sections explain in more detail how selected chromatography techniques are applied in practice.
LC-MS/MS - Environmental and pharmaceutical trace contamination
Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is a variant of LC-MS that differentiates the compounds with the base LC-MS, then fragments and measures the resulting ion products with the second MS. This makes interference much less likely and provides a significantly higher signal to noise ratio in the output, allowing for clear measurements of ultra-trace components in complex matrices with regulatory confidence.
Because of that, this technique is widely used for PFAS analysis and the detection of drug and pesticide residues in complex environmental and biological samples.
LC-UV/DAD - Food and supplements
Liquid chromatography with UV or diode array detection (LC-UV/DAD) separates components with LC, then measures them based on their absorption of light in the ultraviolet to visible range (UV-Vis). This technique is reliable and cost-effective for routine analysis of analytes containing chromophores – structural components of the molecule that have electronic transitions in the UV-Vis range. These compounds, which include various vitamins, preservatives, additives, and sweeteners, are commonly measured in the food and beverage industry.
Py-GC/MS - Microplastics, polymers
Pyrolysis gas chromatography–mass spectrometry (py-GC/MS) thermally decomposes solid samples into characteristic components, which are then analyzed by traditional GC-MS. The key advantage of this approach is that it bypasses any need to extract or dissolve the sample for analysis, enabling a reliable chromatographic analysis of difficult, but thermally decomposable, sample matrices. Some properties that are well-suited for this technique include high-molecular-weight, insoluble, and heterogeneous materials.
Py-GC/MS is commonly used for microplastics analysis, being one of the industry-leading ways to detect nanoplastics. It is also used in the polymer and recycling industries to characterize polymer blends, textiles, and rubber. Biomass, lignin, and feedstocks are also commonly analyzed to characterize lignocellulosic materials.
GC-FID - Hydrocarbons and solvents
Gas chromatography with flame ionization detection (GC-FID) separates volatile compounds and then detects organic compounds by measuring the ions formed following combustion with a hydrogen flame. The output signal is proportional to the amount of carbon in the analyte, regardless of structure, so it has limitations in differentiating compounds with similar amounts of carbon. However, GC-FID measurements are reliable, reproducible, and require little complexity in the analysis, making it a primary method for the quantification of known organic components in the fuels and petroleum industry.
GC-TCD - Biogas, Industrial gas, and natural gas
Gas chromatography with thermal conductivity detection (GC-TCD) separates volatile compounds and then measures the change in thermal conductivity of the carrier gas caused by the analytes it contains. Its traditional use-case is for permanent gases, such as hydrogen, nitrogen, oxygen, methane, and carbon dioxide. Biogas industries also commonly use GC-TCD for reliable quantification of bulk gas components.
Measurlabs’ chromatography services
Measurlabs offers a wide range of chromatography-based analyses for environmental, pharmaceutical, food, polymer, and industrial applications. The following are examples of commonly requested services:
PFAS analysis by LC-MS/MS for water, soil, chemical, and product samples
Microplastic analysis and polymer characterization with py-GC/MS
VOC testing by GC-MS and GC-FID for packaging materials, gases, and environmental samples
Extensive pesticide residue screening by LC-MS/MS and GC-MS/MS in food, feed, and supplements
Gas composition analysis by GC-TCD for biogas and natural gas
Additional chromatography methods and matrices are available on request. Contact our experts using the form below to discuss your specific testing needs.