Acetonitrile in the Pharmaceutical Industry



When there’s a shortage of acetonitrile, it’s big news. If you work in a chemistry lab, or if you manage laboratory orders, you definitely notice when the supply starts to wane. Analytical chemists can’t run most protocols on the HPLC without this essential solvent. Synthetic chemists can’t make many compounds because they don’t have the appropriate substrate. There is hoarding, prices soar, and chemists scramble to find suitable replacements.

This speaks to the critical role acetonitrile plays, in analytical chemistry, synthetic chemistry, and most especially in the pharmaceutical industry. When acetonitrile is scarce or expensive, it creates a huge backlog and a lot of problems. This was most felt most dramatically in 2008, when the economic recession coincided with the Beijing Olympics and Hurricane Ike, all of which had a negative impact on the supply chain. In particular, most acetonitrile is produced as a byproduct of acrylonitrile production. When acrylonitrile production falls, so does acetonitrile supply. This, in addition to other factors, results in a volatile supply of acetonitrile, not only in 2008, but on several subsequent occasions.

Acetonitrile is difficult to replace with other solvents, and difficult to recover and recycle in the appropriate purity. In this article, let’s take a look at what’s so special about acetonitrile as a solvent, and the critical role it plays in the pharmaceutical industry.

What’s so special about acetonitrile?

Acetonitrile is a clear, colorless liquid with a mildly sweet odor. It has lower density than water and vapors that are more dense than water vapor. As the name suggests, acetonitrile is a nitrile, also known as an organic cyanide. It also goes by the name methyl cyanide. That means it has a methyl group (―CH3) bonded to a cyano group (―C ≡ N).

This chemical structure has important implications for the chemical uses of this compound. For example, the strong C―C bond is very difficult to break except under extreme conditions, so acetonitrile is relatively stable as a reaction solvent. For comparison, potential alternatives like methanol and ethanol are much more reactive, and therefore unsuitable for synthesis.

Another important characteristic is the charge distribution of acetonitrile. Although acetonitrile is structurally quite different from water, it actually possesses a similar charge distribution. However, it possesses more intermediate polarity compared to water. Hence, it is able to dissolve both polar and nonpolar substances, which contributes to its versatility as a solvent. For example, in liquid chromatography it is necessary that the mobile phases be miscible. For analytical applications, it is sometimes possible to replace an acetonitrile mobile phase with another solvent if absolutely necessary. However, where acetonitrile is available it is still preferred.

Besides its utility as a reaction solvent, acetonitrile is an important substrate in synthetic chemistry. It becomes a nucleophile via the deprotonation of carbon, or from the lone pair of electrons on the nitrogen atom. It can also be cleaved to produce reactive radicals. It is often used as a source of nitrogen during the synthesis of nitrogen-containing compounds, or as a nitrile source. One reason why acetonitrile is so important to the pharmaceutical industry is because many medicinal compounds have a nitrile group. It can also be used in the synthesis of heterocyclic compounds, which are known for their biological activity.

While acetonitrile is certainly toxic when used improperly, it is still relatively safe compared to other solvents. It also has an acceptable environmental profile compared to many alternatives. These features further contribute to its utility in many industries.

Why is acetonitrile so difficult to recycle?

Due to the volatility of the acetonitrile supply chain, there has been interest in investigating whether or not acetonitrile can be recycled. In fact, acetonitrile is able to be recovered to some extent from chemical waste. However, the purity of recycled acetonitrile has an upper limit that is not appropriate for pharmaceutical or analytical applications.

Pharmaceutical grade is the same as USP grade, which has some of the highest standards for chemical purity available. The reason is obvious: pharmaceuticals and cosmetics, which use USP grade chemicals, need to be of high quality for safety and efficacy. During the acetonitrile shortage, when pharmaceutical companies had to obtain acetonitrile from new suppliers, those suppliers were subjected to stringent testing to ensure quality and safety. Industrial applications may make use of recycled acetonitrile, which would free up more high purity acetonitrile where it’s a requirement.


History has shown that acetonitrile is practically irreplaceable in many industries, the most critical of which is the pharmaceutical industry. Its chemical structure make it uniquely suited as an analytical reagent, reaction solvent, and synthetic substrate – especially as a nitrogen or cyanide source in medicinal compounds. Many critical applications of acetonitrile require high purity, USP grade chemicals that cannot be obtained via recycled waste.


Chen, Genwei, et al. “Acetonitrile formation from ethane or ethylene through anaerobic ammodehydrogenation.” Catalysis Today 416 (2023): 113751.

Gao, Hong, et al. “Bioanalytical solutions to acetonitrile shortages.” Bioanalysis 2.9 (2010): 1627-1640.

McConvey, Ian F., et al. “The importance of acetonitrile in the pharmaceutical industry and opportunities for its recovery from waste.” Organic Process Research & Development 16.4 (2012): 612-624.

Zhong, Pinyong, et al. “Advances in the Application of Acetonitrile in Organic Synthesis since 2018.” Catalysts, vol. 13, no. 4, Apr. 2023, p. 761. Crossref,

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