Microscale HPLC Predicts Preparative Performance at Millionfold Scale

Abstract

The use of microscale HPLC for piloting the large-scale preparative chromatographic resolution of the enantiomers of a chiral pharmaceutical intermediate is reported with an example of a millionfold scale-up from a 300 µm i.d. column to a 30 cm i.d column.Performance and productivity at scale are accurately predicted by the microscale approach, which consumes only a small fraction of the material typically used for conventional loading studies. These results suggest a great potential for use of microscale HPLC loading studies during early synthetic route investigations, when only a small amount of sample is typically available.

Support of academic synthetic chemistry using separation technologies from the pharmaceutical industry

“…[25][26][27][28] Although flash chromatography and preparative TLC are ubiquitous in academic synthetic chemistry laboratories, the use of more sophisticated preparative chromatography techniques is virtually unknown. Microgram amounts of pure compounds can often be obtained by preparative chromatographic separation using conventional analytical columns and equipment, 29 making the technique well-suited for supporting the emerging area of microscale synthesis and characterization. However, larger and more expensive instrumentation is required for gram to kilogram scale separations, making a shared infrastructure model a practical necessity.…”

Preparative-scale separation by simulated moving bed chromatography of biocatalytically produced regioisomeric lactones

“…A new control concept to exploit the full potential of the SMB technology [42], experimentally implemented for the first time in the separation of nucleosides, can render the detailed isotherm measurements redundant and save time in the design of the separation. With the use of microscale HPLC for predicting preparative performance and productivity at millionfold scale [43], separations by simulated moving bed chromatography have a great potential to be included in early phase route selections. …”

Chiral Screening Methods for Pharmaceutical Analysis and Purification in an Industrial Laboratory

“…This system has the advantages of capillary columns cited in Section 3.1. Welch et al [36] recently published a paper describing the use of microscale HPLC for piloting the large-scale preparative chromatographic resolution of the enantiomers of chiral pharmaceutical intermediates. They show a successful million-fold scale-up, from a 300-μm ID column to a 30-cm ID column [36].…”