Automated Selection Of Optimal Purification Conditions From LC/MS And SFC/MS Screening Methods

ASMS 2011, Salt Lake City, UT, USA, 23-27 June 2011, Christine Aurigemma; William Farrell; Joseph Simpkins; Mark Bayliss

Screening methods are a high throughput common approach for accelerating method development for chromatographic separations. Using this approach, several method conditions can be screened in serial or parallel to reduce or eliminate timely method development. However, as the numbers of method conditions are increased, inevitably the amount of time to review and select the optimal condition increases. An automated flexible and dynamic method selection package was implemented to analyze and review both SFC and HPLC screening conditions.


Supercritical Fluid (SFC) and High pressure liquid (HPLC) chromatographic systems were interfaced to single quadrupole mass spectrometric detection. The SFC and HPLC systems consisted of Agilent 1100 LC-MSD’s which include quaternary or binary pumping components, autosampler, Diode Array Detector (DAD) detectors and G1946D MSD Systems. The SFC system also included an Aurora Fusion A5 unit to condition carbon dioxide for use in these experiments. The automated software utilized Analytical Studio Express and Analytical Studio software from Virscidian with customized data interpretation and results visualizations.

Preliminary data

The software was validated against a statistically relevant batch of real world discovery phase pharmaceutical chemistries utilizing 6 SFC and 4 HPLC screening methods. In our initial evaluations of the screening results, the system implementation was able to guide the user to select the best method better than 80% of the time for both SFC and HPLC, though we are still currently optimizing selection criteria and do expect improvements. A target of better than 95% in both cases is the ideal goal for the project once it goes into routine operation. The subsequent methods were purified and the success rate of the purification was found to meet or exceed our corporate needs for purified compound for downstream operations. Additionally, the increase in throughput for lab personnel resulted in an overall drop in turnaround time by 15 – 20% though this is still being optimized. Figure1 shows the visualization of an example analysis and results visualization from the approach. This approach was taken to enable our laboratory to use the best in class instrument, automation and software elements in order to deliver the optimize solution. During the presentation we will provide an overview of the system, its implementation, available performance figures, the challenges which were faced and some of the approaches that have been used to solve these issues.

Novel aspect

Selective scoring and visualization of the practical separation method conditions for SFC-MS and HPLC-MS methodologies using advanced data evaluation criteria.