Bioanalytical solutions to acetonitrile shortages
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Updated: Jun 6, 2026

The Application of Open Searching-based Approaches for the Identification of Acinetobacter baumannii O-linked Glycopeptides
Published on: November 2, 2021
Hong Gao1, John Williams, Scott Carrier
1Vertex Pharmaceuticals Inc., 130 Waverly St, Cambridge, MA 02139, USA. Hong_Gao@vrtx.com
Abstract:
The acetonitrile shortage during 2008 to 2009 challenged bioanalytical scientists due to the ubiquitous role that acetonitrile plays in sample preparation and analysis. Replacement, reduction and reuse of acetonitrile were the core tenants behind each approach used to tackle the shortage. Sample preparation of biological matrices can be accomplished by protein precipitation using a variety of solvents; methanol is usually the best substitute for acetonitrile. The potential liabilities in using methanol can be handled with appropriate modifications. Often methanol is superior to acetonitrile for both protein precipitation and chromatography if phospholipid interference is a problem. Solvent consumption can be minimized by reducing column dimensions and particle size. Separations can be achieved at greatly reduced run times using sub-2-μm and fused-core particle columns. Emerging technologies, such as desorption ESI, direct analysis in real time and laser diode thermal desorption, eliminate the need for chromatography and achieve significant solvent and time savings. Acetonitrile recyclers can purify HPLC waste for reuse.

