Page 11 - LC-SFC_Pharma_Brochure

C190-E170

Technical Rapid Method Scouting of
Report Chiral Compounds

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Tadayuki Yamaguchi , Hidetoshi Terada , Takeo Sakai , Sadahiro Hayakawa 1
Abstract:

Enantiomer resolution by chiral column chromatography is a variation of column chromatography that is actively being researched in the
pharmaceutical field of drug discovery. One drawback of this method, however, is the extensive time and effort required to determine the
optimum mobile phase conditions and the most suitable column for separation of the analyte among a wide variety of available chiral columns.
This has spurred the demand for faster scouting of chiral separation conditions.
Here, using the Nexera Method Scouting system with the iChiral-6 polysaccharide-based columns (Daicel Corporation), we report an example in
which high-resolution column conditions are constructed for analysis of chiral compounds.
Keywords: UHPLC, Nexera Method Scouting, chiral column, iChiral-6, chiral compounds

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1. Introduction creasing overall throughput while minimizing solvent consumption.
Intr
oduction
The safe and secure use of chiral compounds in their pure form Here we introduce the results obtained in the analysis of three chiral
(enantiomers) is essential for direct biological applications, specifically compounds: bromacil, α-methyl-α-acethyl-γ-butylrolactone, and meth-
in the field of pharmaceuticals. It is often the case where one enantio- ylclothiazide using the Nexera Method Scouting system with the high-
mer has detrimental or toxic effects while the other enantiomer has resolution conditions that are possible with the iChiral-6 polysaccha-
curative properties, so it is critical that enantiomers be fully separated. ride-based columns.
Optical separation (chiral separation) by HPLC is one method typically
used to obtain chiral compounds. This HPLC method normally in-
2. Experiment
volves a labor-intensive, time-consuming search for an appropriate 2. Experiment
mobile phase and column suitable for a particular chiral compound, a
2-1. System
process referred to as method scouting. Much effort has been direct-
ed recently at accelerating such method scouting to speed up drug
Fig. 1 shows the flow diagram depicting the Nexera Method Scouting
synthesis and the production of pharmaceutical intermediates.
system that was constructed for this application. The system is config-
As an associated technology, ultra high performance liquid chroma- ured by installing a column switching valve inside the oven and a sol-
tography (UHPLC) has been attracting much attention as an HPLC vent switching valve within each of the Nexera ultra high perfor-
technique capable of increasing throughput in commercial analytical mance pump, thereby permitting comprehensive data collection
enterprises by improving productivity and efficiency. Introduction of while continuously switching through a maximum of 96 unique com-
UHPLC is also being promoted for method scouting as a means of in- binations of columns and mobile phases.

CHIRALPAK IA
CHIRALPAK IB
n-Hexane
Pump A Gradient
Dichloromethane CHIRALPAK IC
mixer Autoinjector PDA
Methyl tert-Butyl Ether LPGE unit
2-Propanol
CHIRALPAK ID
2-Propanol Column CHIRALPAK IE
Pump B switching
Ethanol
valve CHIRALPAK IF
Dichloromethane LPGE unit
Column oven
Methyl tert-Butyl Ether
Fig. 1 Flow Diagram of the Nexera Method Scouting System
1 Analytical & Measuring Instruments Division 1