Since last fall, labs worldwide have struggled to cope with a shortage of acetonitrile (ACN), the most commonly used organic solvent for LC mobile phase. Companies supplying LC products have responded with information, support and solutions for end-users looking to conserve the now precious chemical compound, for which prices have skyrocketed.

ACN suppliers’ measures have included rationing ACN supplies, limiting orders to existing customers and raising prices. Updating the situation, Russell Thorpe, director of Marketing for Mallinckrodt Baker, told IBO: “we are optimistic that this will result in some temporary relief in supply over the next two to three months, but we do not expect supply to return to pre-shortage quantities until later in calendar year 2009 and possibly the first quarter of 2010.”

To conserve ACN, chromatographers have several short-term solutions. One solution is to use a column with a smaller internal diameter, or a shorter column with a smaller particle size. Alternatively, chromatographers can use another solvent, such as methanol or ethanol. Solvent recyclers are an additional option.

Longer-term solutions, which require a greater upfront investment of time and money, include changing methods or changing LC systems. Changing methods requires method development and, for labs using validated methods, revalidation. Fast LC, UHPLC or UPLC systems, which are designed to be used at higher pressures with smaller particle columns, are another choice.

Jason Lim, Brand manager for chromatography columns supplier Phenomenex, told IBO that changing columns has been the most popular solution for his company’s customers. “That’s been popular because it requires very little revalidation of their method and because the packing material of the column is the same.” Reducing column length, internal diameter (ID) and particle size can reduce solvent usage by as much as 80%, according to Phenomenex. Maureen Joseph, LC Columns manager for Agilent Technologies, told IBO that sales of Agilent’s 1200 Series LC Method Development System, Solvent Saver 3.0 mm ID columns and 1.8µm Rapid Resolution High Throughput columns have all increased.

As with changing columns, switching solvents is also an simple solution. “Methanol is a very popular alternative because it has relatively the same elution strength as acetonitrile. It’s actually a little bit weaker, so [customers] do have to do a little bit of development just to get the same amount of separation and retention that they did with acetonitrile,” said Mr. Lim. Both Ms. Joseph and Mr. Lim noted that their companies have been getting more technical questions about converting to methanol. Mr. Thorpe told IBO that Mallinckrodt Baker has seen an increase in demand for methanol.

As Michael Frank, product manager for Pharmaceutical Solution at Agilent, asserted, changing columns or solvents is also a cost-effective solution. “Due to the current global economic recession, companies tend to look for measures to save acetonitrile without large capital investments like new instruments.” Methanol is also being used in developing new methods. “We have seen customers in regulated environments preferentially trying methanol when they develop new methods. This is to avoid putting themselves in a bad position if the acetonitrile shortage continues,” he said.

However, a new system, while initially expensive and time consuming, may be the most cost-effective solution in the long run, according to Ray Himmel, senior director of ACQUITY UPLC Business Development for Waters. He stated that UPLC can reduce solvent usage by 90%–95% compared to HPLC and by 50% compared to UHPLC or fast LC. UPLC columns have IDs of 2.1 mm or 1 mm, and the system has a internal volume of 85µL compared to internal volumes of 350 mL for UHPLC and 800–900 mL for HPLC. “The volume of the system must be ‘swept’ each time a sample is analyzed, producing an equal volume of solvent for disposal,” he explained. He also said that UPLC is better able to handle the higher back pressures resulting from methanol’s higher viscosity. Solvent suppliers have also recognized these advantages. To reduce solvent usage by optimizing the performance of ultra high pressure systems, Mallinckrodt Baker has released JT Baker ULTRA LC/MS solvents, which extend column life.

In fact, as Mr. Lim noted, the ACN shortage is part of an LC market trend. “The whole industry in the past five years has been moving toward miniaturization, so smaller particles, smaller columns [and] faster analysis. But this acetonitrile shortage has just been more of a driver to get people to do that even faster.”