Green Chemistry

Separation techniques following green chemistry practices are becoming more important as solvent disposal costs increase and laboratories move toward decreasing solvent consumption and the generation of hazardous waste. Participants in this Technology Forum are Helmut Schulenberg-Schell of Agilent Technologies, Sergio Guazzotti and Eric Phillips of Thermo Fisher Scientific, and Elizabeth Hodgdon and David Wetherell of Waters Corp.

Which separation techniques are the most compatible with green chemistry? Which aren’t?

Schulenberg-Schell: Conventional liquid chromatography (LC) requiring long run times on large i.d. columns can create a substantial amount of waste and consume considerable amounts of energy. A wide range of alternatives are available to seamlessly transfer to state-of-the-art ultrahigh-pressure liquid chromatography (UHPLC) instrumentation and column technology. This accelerates LC separations down to run times of a few minutes or even seconds. In addition supercritical fluid chromatography (SFC) and capillary electrophoresis (CE) instruments are available for analytical laboratories. Both techniques are extremely fast and will not create significant amount of organic solvent waste at all. In addition they can be used as orthogonal methodology to confirm results from LC separations.

Guazzotti and Phillips:Green techniques have to do with minimizing or eliminating the hazardous waste associated with laboratories. This can be done by moving to gas chromatography (GC) techniques that do not require solvent for separation. Regarding LC, this can be done by changing to a less or nonhazardous solvent or by using UHPLC. By utilizing UHPLC the amount of solvent needed to carry out separations is significantly reduced without sacrificing the actual separation resolution. The term “green” needs to be applied to the entire method, from extraction to analysis and even reporting.

Hodgdon and Wetherell:SFC certainly offers some distinct advantages, from a green perspective, by eliminating many of the traditional solvents utilized in HPLC. By using carbon dioxide as the primary mobile phase, in combination with small amounts of organic modifier, typically methanol, we can achieve faster separations, and produce significantly less organic waste in the process.

Like SFC, sub-2-µm LC systems and particle chemistries offer a way to scale high performance liquid chromatography (HPLC) flow rates and hence solvent usage, without compromising performance. This is because reducing inner diameter and column length can have a significant impact on solvent consumption. Additionally, the increased efficiency of small particles offers the ability to reduce the analysis time, further reducing solvent consumption and environmental impact.

Which green separation techniques have been the most widely implemented?

Schulenberg-Schell:UHPLC has created the most buzz recently; however, there is a substantial installed base for CE and SFC as well. CE has a strong footprint in biopharmaceutical, food, and forensic applications where charged compounds are of high interest. SFC has the advantage of scalability from analytical to prep scale.

Guazzotti and Phillips:There is a focus on how to change the way all sample preparation and separations are done to minimize the hazardous waste. This has been done on all techniques, GC and LC. The biggest change recently has been on the LC separations. There has been a move to lower volumes and faster run times to give better separations and faster run times. This also has the effect of lower consumption of solvent. UHPLC has been widely applied, with significant growth since its first introduction in 2004.

Hodgdon and Wetherell:The key to embracing change is to offer a way to improve efficiencies and lower costs at the same time. Sub-2-µm LC has demonstrated this conclusively. Many companies wish to be more environmentally conscientious but to access these improvements and make the investment solid, return-on-investment (ROI) benefits need to be demonstrated. The acetonitrile shortage has now passed, but this event accelerated many companies to access sub-2-µm particle technology. Now, systems are being designed that allow users to future-proof their labs, to run HPLC now, but with the ability to access sub-2-µm LC to take advantage of solvent and disposal cost savings where the technique can be proved most effective.

Has automation decreased solvent consumption? What other techniques can chemists use to decrease solvent consumption?

Schulenberg-Schell:Automation can come in different ways to the lab. If simple manual procedures are executed by robots there will be no significant savings. If automation goes along with a downscaling of sample amounts required per analysis this can help tremendously to save solvents. With the state-of the art detector sensitivity this is possible. UV diode-array detectors allow analyses to start from much smaller sample amounts and still achieve the required limits of detection (LOD).

Guazzotti and Phillips:Although automated techniques may appear to increase solvent consumption, they generally decrease it. There is less opportunity for spills, the waste is handled in a more appropriate manner and there is the move to less hazardous solvents. Sample preparation is one area that can continue to decrease solvent use. Techniques that minimize and eliminate solvents are not only preferable from an environmental impact side but also can be more economical for the lab.

In LC applications one approach that can be used for HPLC as well as UHPLC is carrying out isocratic separation and recycling the mobile phase with the help of automatic recyclers. The combination of temperature programming with isocratic separations and recycling certainly offers several advantages since in this case the polarity of the mobile phases changes with temperature and therefore optimal separations can be achieved for many applications.

Hodgdon and Wetherell:By analyzing customer needs practical and perceptive automation features can be developed by suppliers, and these do not have to be overly complex. For example, a new system optimizes solvent usage by automatically blending up to four solvents in accurate proportions. There is no requirement to make up a number of specific mobile phase bottles, which will be discarded after perhaps only one use. Instead, users can proportion smaller volumes of concentrated solvents in any sequence for isocratic or binary, ternary, and quaternary gradients. Not only is the amount of solvent usage limited for applications such as automatic method development or system flushing, it is simplified and routine assays become more rugged as less human error is introduced. Further, in the latest iteration of the technology, the user can program methods directly in units of pH and molarity, again simplifying the use of buffer stocks that can be prepared in smaller batches.

What have been the biggest hurdles for chemists in implementing green chemistry techniques?

Schulenberg-Schell:In many industries we are dealing with methodology that is subject to regulation. Unfortunately a lot of conventional technology has been recommended or declared as mandatory in these documents. Changing the regulatory guidance can be very time-consuming and expensive to do. Solutions to help with rapid method development and validation of new methods can significantly cut down the time for transition.

Guazzotti and Phillips:The belief that standard methods cannot be changed or altered and the speed at which agencies change has been a big hurdle. There is also a significant investment in time and resources to change methods to use either different sample prep techniques or different solvents for LC separations. One hurdle for the implementation of UHPLC has been the need to revalidate methods if the modifications needed to scale the separations from HPLC to UHPLC did not fall within the parameters’ variability allowed by the USP.

Hodgdon and Wetherell:For SFC we see that many customers are just not familiar with the current technology, and the advantages it provides in the laboratory for normal-phase analysis and purification. As manufacturers we need to increase the visibility of SFC as a mainstream laboratory tool, and also help customers understand the value it provides from a green chemistry perspective. Flexible platforms will be developed that can run multiple techniques, as well as targeted chemistries that allow simple method development and transfer strategies and software that accelerates method development.

Propagating sub-2-µm LC methods in place of conventional HPLC methods is dependent on the availability of tools and practices to assist in managing change. Nevertheless, for both SFC and sub-2-µm LC the hurdle remains that regulatory practices, particularly compendial chromatographic procedures do not provide the necessary flexibility to change the chromatographic column without the necessity of revalidation of the method.

What trends can we expect to see in the future with green chemistry, particularly with regard to separation techniques?

Schulenberg-Schell:We observe a few commercial companies and regulatory bodies taking a strong interest and we expect that much larger numbers of users will quickly learn and adopt the new green chemistry. The savings for a better future, the quality of life, and the economic benefits are so significant that this is the place to be.

Guazzotti and Phillips:There will be a continual drive to use less solvent and solvents that are less hazardous. Sample preparation will be a very large focus as will the solvents used in LC. The laboratories that make the best use of the idea of green chemistry will not only benefit the environment but they will benefit their profits. The lab will become more profitable because there will be less spent on collecting, storing, and disposal of hazardous waste. In addition, in LC we can expect to see a continuous increase in the adoption of UHPLC as well as scaling down separations to reduce the amount of mobile phases needed to carry out separations.

Hodgdon and Wetherell: We are now beginning to see the next generation of SFC instrument hardware, as well as new column chemistries for both SFC and HPLC, resulting in shorter analysis times, with improved resolution. This will further enhance the green aspects of this technology by reducing solvent consumption, as well as the generation of hazardous organic waste.

In these days of Lean Manufacturing and Six Sigma, companies are implementing business strategies and are carefully analyzing operations to improve overall efficiency, lower costs, increase quality, and add, change, or eliminate activities and processes to improve overall performance. It is likely that instrumentation will continue to scale separations to a smaller scale. The advantages of reducing consumption are complemented by the advantages of increased sensitivity, as dilution is reduced, while separation quality is maintained. Reduction in flow rates complements mass spectrometry detection, which is moving closer to the QA/QC lab and manufacturing floor. Generally, companies are looking at platform changes that offer economy of scale and maintain flexibility.

If you are interested in participating in any upcoming Technology Forums please contact Group Technical Editor Steve Brown or Associate Editor Meg Evans for more information. Next month’s forums will focus on the GC and HPLC/UHPLC markets.