Acetonitrile (sometimes searched as “acetone nitrile”, though it is a different compound from acetone) is the workhorse solvent of reversed-phase HPLC and LC-MS. It is also used in peptide synthesis, DNA synthesis and organic chemistry. This guide explains why chromatographers rely on it, which grade to buy, why supply sometimes gets tight, and how to handle it safely.
Key facts
| Name | Acetonitrile (methyl cyanide), CH₃CN |
|---|---|
| CAS number | 75-05-8 |
| Appearance | Clear, colourless liquid |
| Hazards | Highly flammable; harmful by inhalation, ingestion and skin contact; eye irritant |
| Not to be confused with | Acetone (propan-2-one), a different solvent |
Why acetonitrile is the HPLC solvent of choice
- Low UV cut-off, so it does not interfere with detection at short wavelengths.
- Low viscosity when mixed with water, which keeps back-pressure down.
- Strong elution in reversed-phase chromatography and good peak shapes.
- Compatible with mass spectrometry because it is volatile.
Choosing the right grade
Buy the lowest grade that meets your method’s needs. LC-MS grade is tested for ions and contaminants that create background noise and adducts in mass spectrometry, and costs considerably more. For other solvent and reagent grades, see Reagent Chemicals Explained.
Why acetonitrile supply can be tight
Most acetonitrile is a by-product of manufacturing acrylonitrile, a chemical used to make plastics and fibres. When acrylonitrile production falls, so does acetonitrile supply, regardless of lab demand. This happened notably during the 2008–2009 economic downturn, when prices for HPLC-grade acetonitrile rose sharply and some labs struggled to get it. Lessons from that shortage still apply:
- Qualify a second supplier and grade before you need it.
- Keep a sensible safety stock without over-buying.
- Consider methods that use less solvent: narrower columns, shorter runs or UHPLC.
- Recycle acetonitrile from isocratic methods where your quality system allows.
Alternatives
Methanol is the most common substitute in reversed-phase HPLC. It is cheaper and more widely available, but has higher viscosity with water and a higher UV cut-off, and it changes selectivity, so methods need revalidation. Ethanol and isopropanol are used in some greener methods.
Safe handling, storage and disposal
- Store in a flammables cabinet away from oxidisers and ignition sources.
- Use in a fume cupboard or well-ventilated area; avoid skin contact. Acetonitrile is metabolised in the body to cyanide, so poisoning symptoms can be delayed.
- Use suitable gloves; check the manufacturer’s chemical resistance data, as thin nitrile gloves give limited protection.
- Collect waste separately and dispose of it through a licensed hazardous waste contractor. Never pour it down the drain.
Frequently asked questions
Is acetone nitrile the same as acetonitrile?
“Acetone nitrile” is a common misspelling of acetonitrile. Acetone is a different solvent.
Can I use HPLC grade acetonitrile for LC-MS?
Sometimes, but LC-MS grade reduces background noise and adducts, so it is safer for sensitive work.
Why is acetonitrile sometimes hard to get?
Because it is mainly a by-product of acrylonitrile production, supply depends on demand for plastics and fibres, not just lab demand.
