LAB · Published 2026-10-13
HPLC vs GC: choosing chromatography equipment for your lab
Choose GC when your analytes are volatile and stay stable when heated: solvents, fuels, fragrances, many pesticides. Choose HPLC when they are not: drug substances and their impurities, sugars, peptides, most polar or heavy molecules. The sample decides first. Detectors, throughput, utilities and budget come after that, and many labs end up running both because their sample list crosses the line.
What is the difference between HPLC and GC?
Both separate a mixture by passing it through a column, where each compound moves at its own speed. In gas chromatography the mobile phase is an inert carrier gas, typically helium, hydrogen or nitrogen, and the column sits in an oven whose temperature is programmed during the run. The sample has to be vaporized at the inlet, which is why it must be volatile and thermally stable.
In high-performance liquid chromatography a pump pushes a liquid mobile phase under high pressure through a column packed with fine particles. Separation happens at or near room temperature, so heat-sensitive and non-volatile compounds are no problem. UHPLC is the same principle with smaller particles and higher pressures, which gives faster runs and sharper peaks.
| GC | HPLC | |
|---|---|---|
| Mobile phase | Carrier gas: helium, hydrogen, nitrogen | Solvent mixture, e.g. water with acetonitrile or methanol |
| Sample must be | Volatile and thermally stable | Soluble in the mobile phase |
| Typical columns | Long open-tubular capillary columns | Short packed columns, reversed phase most common |
| Common detectors | FID, TCD, ECD, mass spectrometer | UV/Vis or diode array, fluorescence, refractive index, mass spectrometer |
| Running consumables | Gases, septa, liners, columns | Solvents, solvent waste, columns, seals |
| Typical work | Residual solvents, VOCs, petrochemicals, essential oils | Drug assay and impurities, dissolution, vitamins, proteins |
What is GC used for?
GC is the standard tool for volatile organic compounds. Pharmaceutical labs use headspace GC to measure residual solvents. Environmental labs test air, water and soil for VOCs. Refineries profile fuels and gases, and flavor and fragrance labs separate essential oils into dozens of components. Coupled to a mass spectrometer, GC-MS identifies unknown peaks against spectral libraries.
Some compounds that are not volatile on their own, such as fatty acids, can be derivatized into volatile forms and analyzed by GC. That works, but it adds a sample preparation step that HPLC often avoids.
What is HPLC used for?
HPLC covers the large part of chemistry that would decompose in a GC inlet. In pharmaceutical QC it handles assay, related substances and dissolution testing. Food labs measure additives, vitamins and sugars. Biotech labs separate proteins and peptides by size exclusion or ion exchange. LC-MS adds the identification power of mass spectrometry to all of this.
Detector choice shapes the system as much as the pump does. A diode array detector covers most compounds with a chromophore and records a spectrum for each peak. Fluorescence is far more selective for the compounds that fluoresce. A refractive index detector sees sugars and polymers that absorb little UV, but it does not work with gradient elution. If you cannot name a detector that sees all your analytes, plan for MS from the start.
How to choose a chromatography system
Start with a written sample list: compounds, matrices, expected concentrations and the methods you must follow. Pharmacopoeial methods, for example those built on USP general chapter 621, often fix the technique and the column type for you.
If the budget allows only one instrument this year, buy for the samples that bring in the most work and outsource the rest until volume justifies a second system. A GC bought for a few residual solvent tests a month can sit idle while the LC queue grows. Then work through the rest of the specification.
- Sensitivity: is a UV or FID detector enough, or do you need MS?
- Throughput: autosampler capacity and run time per sample
- Data integrity: software that supports audit trails if you work under FDA 21 CFR Part 11 or GMP
- Utilities: gas supply or generators for GC, solvent supply and waste handling for HPLC
- Service: local engineers, spare parts and consumables for the exact model
- Method transfer: whether existing methods run on the new system without revalidation
Which manufacturers build HPLC and GC systems?
Several makers cover both techniques. Agilent Technologies builds liquid chromatography and LC/MS systems as well as gas chromatographs, GC/MS and its J&W GC columns. Shimadzu offers LC, LC-MS, GC and GC-MS alongside spectroscopy and other analyzers. Thermo Fisher Scientific sells chromatography systems and columns under its Thermo Scientific brand.
Waters concentrates on liquid chromatography and mass spectrometry, with ACQUITY and Alliance systems, Xevo mass spectrometers and columns for HPLC, UPLC and UHPLC. If your lab is mostly LC, that focus can be an advantage. The full list of instrument makers we source from is in our laboratory equipment supplier section. Send us your sample list or the part numbers of your current system, and we will propose configurations and prices on request.