Strategic choices to reduce acetonitrile dependence

By Richard Lake, Pharmaceutical Market Development Manager, Restek Corporation

In today’s economic climate, laboratory productivity is an increasingly important key to bringing new drugs to market efficiently, and the current acetonitrile shortage has created a significant challenge to productivity for many labs.

Acetonitrile is the most widely used organic solvent in the pharmaceutical industry, and suppliers have indicated that rationing and/or cost increases should be expected until at least the end of the year. While the duration of this shortage is unknown, it presents an opportunity to review laboratory practices and make strategic changes. This article presents both short-term solutions for reducing costs by cutting current consumption levels and long-term method development tactics for reducing overall dependence.

Using smaller columns is one of the most commonly recommended ways to reduce acetonitrile consumption over the short term. By decreasing the internal diameter of the analytical column, a 52-80 percent reduction in solvent consumption can easily be achieved (values vary based on system performance and method parameters). Larger diameter columns require higher flow rates, and thus larger volumes of mobile phase, to reach the desired linear velocity. Reducing column inner diameter is a simple way to decrease the volume of acetonitrile used, while maintaining equivalent method performance.

Switching to an alternate solvent system is also often cited as a short-term solution. While viable, this fix is not as simple as it may appear. With alternate solvent systems, the chemical properties often differ and prior to implementation several points must be considered, including: mode of separation, detector issues (such as UV cutoff) and analyte compatibility. Revalidation is usually necessary when an alternate solvent is used, thus, using smaller diameter columns is generally the easiest, most immediate way to reduce acetonitrile use. Details on implementing both strategies are available at www.restek.com/acetonitrile.

Another way to reduce solvent consumption is by implementing fast LC through ultra high-pressure liquid chromatography (UHPLC). UHPLC, due to greater efficiency and linear velocity, can reduce analysis time by as much as 5-10 fold. UHPLC is a viable short-term solution for labs that have already adopted this technology. However, UHPLC equipment can require a substantial capital expenditure, and labs that have not invested in these systems yet may be reluctant to do so in the current economic climate. Labs interested in the benefits and practical applications of UHPLC can find more information at www.restek.com/uhplc.

While there are several short-term solutions available, these techniques are not always optimal over the long term. In order to reduce dependence on acetonitrile over the long term, labs must focus on developing methods on columns that perform better with other solvents. While C18 columns are the most commonly used phase in drug development, other phases can give better performance with alternate mobile phases. For example, phenyl columns are more retentive and provide alternate selectivity when using methanol instead of acetonitrile. [1] Restek has developed a Biphenyl phase, which is comparable to C18 and other phenyl columns when used with acetonitrile, but provides much greater retention and selectivity than other phases when used with methanol. This versatility makes them ideal for method development with either solvent. For more information on the practical use of Biphenyl columns, visit www.restek.com/biphenyl.

Over the long term, method development strategies that optimize chromatographic column properties can make laboratories less vulnerable to solvent supply fluctuations. While short-term solutions can solve immediate needs, long-term strategies that invest in versatile column chemistries will be necessary in order to maintain development timelines and overall laboratory productivity. 

Restek is committed to helping chromatographers through trustworthy and sound technical advice. For help selecting and implementing a solvent-reducing strategy, contact us at 800-356-1688 ext. 4 or at support@restek.com.

References
[1] M. Yang, S. Fazio, D. Munch, P. Drumm, J. Chromatogr. A. 1097 (2005) 124.

Richard Lake is the Pharmaceutical Market Development Manager at Restek Corporation. He is responsible for overseeing the development and application of chromatographic products for the pharmaceutical industry. He has over 13 years of experience including positions as lead chemist, LC and GC method developer, stability managerand study director for pharmaceutical studies.