Is it OK to use THF (tetrahydrofuran) on my HPLC?

Well, it might be. In the early days of HPLC, THF was commonly used as a mobile phase solvent. It has eluting strength similar to acetonitrile, but just slightly stronger. Since it technically is an ether and is very miscible with water, it is sometimes useful with reverse phase HPLC. It also provides additional options for ternary mixes when methanol/water or acetonitrile/water mobile phases are not able to produce a fine tuned separation.

Like many organic solvents, there are some possible health hazards associated, which you can read about here. THF has a very low boiling point (66C) and emits fairly noxious fumes at room temperature, making it quite unpleasant to work with. You definitely need to use this in a hood.

A more concrete to reason to limit usage of THF for HPLC mobile phase is that it does have a tendency to swell PEEK (polyetheretherketone) material and may contribute to degradation over time. A side effect of the swelling could be increased system pressure, which may become an issue. The use of PEEK tubing and fittings has increased dramatically over the years, due to its ease of usage compared to stainless steel parts. However, THF should not be used with PEEK tubing, unless it is present only at low levels. I have read varying opinions on how much THF one should try using. Personally, I would prefer to stay less than 10% if using PEEK tubing. There is also the possibility that THF at higher levels can degrade other plastic-like materials, for example, pump seals. When using THF, it always best to check with the instrument manufacturer to ensure the proper seals are being used. Some pump seals are designed only for use with aqueous solutions and weaker organic solvents (these would be ones designated as “aqueous” or “reverse phase”).

As far as detection methods go, THF is OK to use for UV detection methods. Since its UV cutoff is around 212 nm, it usually does not produce interference. However, it is important to use HPLC-grade THF to avoid interference from stabilizers that often are used with other solvent grades. It is also important to make sure the THF is fresh, as the formation of peroxides over time will increase the UV background. Usage of THF for PDA and fluorescence detection is fairly similar and the same precautions exist. Some of the same concerns about purity, stabilizers and peroxides apply to most detection methods, including refractive index (RI) detectors.

Using THF with mass spec detectors presents some unique concerns. Agilent and Waters both suggest that its use for LC/MS should be very limited and special precautions should be taken:

Use of THF with LC/MS (Agilent)

Solvents and Caveats for LC/MS (Waters)

ThermoScientific mentions similar precautions for Charged Aerosol Detectors below:

Optimizing and Monitoring Solvent Quality for UV-Vis Absorption, Fluorescence and Charged Aerosol Detectors (ThermoScientific)


I hope you have found this information useful. Thank you for reading.

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