title: Parallel supercritical fluid chromatography/mass spectrometry system for high-throughput enantioselective optimization and separation.
abstract: An automated parallel four-column supercritical fluid chromatography (SFC)/MS system to perform high-throughput enantioselective chromatographic method development and optimization is described in this paper. The initial screening was performed in parallel on four chiral SFC columns over several buffer conditions. Optimization of the separation of enantiomers was achieved on a single chiral column. The screening and optimization were accomplished in a fully automated, user-independent manner. Incorporation of column control valves in front of each chiral column allowed the system to switch from parallel four-column screening mode to single-column optimization mode. To facilitate the process, a custom software program, we termed, intelligent parallel optimization for chiral SFC separation (IPOCSS), was developed in-house. The custom software monitored each of the runs in real-time, processed each data set, and by incorporating user-defined criteria (e.g., resolution of the two enantiomer chromatographic peaks), selected the next set of experiments and automatically optimized the enantioseparation. This new approach, combining parallel SFC/MS screening and intelligent software-controlled method optimization, has resulted in a streamlined, high-throughput tool for enantioselective method development, which has been applied successfully to enantioseparations in support of drug discovery.
authors: Takeda San Diego, Inc., 10410 Science Center Drive, San Diego, CA 92121, USA.
authors: Lu
authors: L
authors: Zeng
authors: Rongda
authors: R
authors: Xu
authors: Derek B
authors: DB
authors: Laskar
authors: Daniel B
authors: DB
authors: Kassel
mesh_terms: D001331:Automation / Q000379:methods / Q000592:standards; D005591:Chemical Fractionation / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D025924:Chromatography, Supercritical Fluid / Q000295:instrumentation* / Q000379:methods*; D007202:Indicators and Reagents; D013058:Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D012984:Software; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013237:Stereoisomerism; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature
chemical_list: D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D012997:Solvents