Life cycle analysis and sustainability comparison of reversed phase high performance liquid chromatography and carbon dioxide-containing chromatography of small molecule pharmaceuticals

The greenness of a chromatographic separation is typically determined by examining the solvent selection and the quantity of solvent used. Carbon dioxide is often touted as a green alternative to organic solvents typically used in chromatography. However, this claim does not consider the additional instrumentation and energy requirements needed for its use in supercritical fluid chromatography (SFC) compared to alternative methods such as reversed phase (RP) high-performance liquid chromatography (HPLC). This work demonstrates the importance of considering not just the solvent usage but also the instrumental energy consumption especially at the analytical scale where it can account for the majority of the emissions of the system. Two methods that use a more holistic characterization of greenness are life cycle analysis (LCA) and the analytical method greenness score (AMGS). The AMGS calculator is a relatively new method of determining greenness so the result from the AMGS calculator is benchmarked to the LCA results. The greenness of both chromatographic systems are compared at both the analytical and preparative scale for the separation of small molecule drug molecules. In general, SFC separations at low flow rates (<3 mL min−1) performed unfavorably when compared to comparable RP-HPLC separations. The influence of chromatographic conditions for SFC, such as flow rate and higher back pressures, are shown to improve the overall greenness of this technique. SFC separations were in general favorable or at least comparable to the RP-HPLC separations when the SFC separations were faster. Lastly, the electrical energy sources used for instruments were demonstrated to reduce the impact of instrument energy consumption at all scales.