The Column - May 2009 - (Page 31)

May 2009 The Column Ali, Kocergin and Edwin Multicolumn Preparative SFC: An Advanced Solution to Scale-up Difficulties Zahid Ali, Jelena Kocergin and Vinay Edwin, Regis Technologies, Inc., Morton Grove, Illinois, USA Drug companies typically require bulk amounts of material for standards, intermediates and final active pharmaceutical ingredients (APIs) as development moves into toxicology and preclinical stages. This quantity of compound is needed quickly, at high purity and at a reasonable price for projects to move forward. Preparative supercritical fluid chromatography (SFC) using chiral columns has gained acceptance as one of the fastest and most cost effective ways to obtain bulk amounts of pure enantiomers. Scale-up to a larger preparative column to obtain gramto-kilogram quantities starts with an analytical separation that shows good resolution. However, even when the data suggests a compound is a good candidate for scale-up, the transition from analytical to preparative scale is not always a smooth one. In the course of transferring an analytical method to the preparative scale, sometimes the data does not conform to the productivity rates predicted by the analytical loading estimation, making multikilogram projects unfeasible in terms of time and cost. Although many factors contribute to a compound’s inability to scale-up linearly, a solution must be found simply and quickly. Here we present a solution using serial chiral stationary phase columns for preparative separations of compounds that are difficult to scale up. The serial-column preparative SFC method increases productivity for fast recovery of optimal amounts of high-quality material compared with single-column methods. We have optimized this approach and have used it routinely for multikilogram separation projects, making otherwise unscaleable projects both feasible and affordable. Contact author: E-mail: Vinay Edwin Experimental Analytical SFC employed the Discovery Series SFC System (TharSFC, a Waters Company, Pittsburgh, Pennsylvania, USA), which has a maximum flow rate of 10 mL/min and UV detection. Preparative SFC employed the SFC Prep 350 (TharSFC, a Waters Company), which has a maximum flow-rate of 350 g/min and UV detection. Multicolumn preparative SFC employed a multicolumn system developed by connecting two preparative SFC columns in series with a simple coupling connector. Results and Discussion Analytical SFC: Screening of a compound at the analytical scale is the first step in the purification process. In this example, analytical SFC screening of an undisclosed drug compound was performed. Two analyses were performed using different commercially available chiral columns: (S,S)Whelk-O1 and RegisCell (Regis Technologies, Morton Grove, Illinois, USA). As the data in Figure 1 shows, the (S,S)Whelk-O1 column provides partial resolution of components [Figure 1(a)], while the RegisCell column generated baseline resolution [Figure 1(b)]. The latter results indicate that this compound is a candidate for scale-up. Single-column preparative SFC: Optimal productivity rates typically are reached by increasing sample load until acceptable levels of loading and resolution are achieved. Resolution, sample load and throughput 31

Table of Contents for the Digital Edition of The Column - May 2009

The Column - May 2009
Q&A: Is Green the New Black?
Market Trends and Analysis
Quantification of Pharmaceuticals from Diminishing Small Volumes of Blood Using the UHC Small Molecule Chip Coupled to Triple Quadrupole MS
An Investigation of the Impact of Common Experimental Parameters on Signal Intensity in SFC–ESI-MS
Multicolumn Preparative SFC: An Advanced Solution to Scale-up Difficulties
Introduction to HPLC 2009
HPLC 2009 Guide

The Column - May 2009