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5. Chiral Separation
            5.  Chiral Separation
            In the field of pharmaceuticals, research is underway in the area of drug
            discovery using chiral columns for rapid chiral separation. Finding the
            appropriate combination of analytical column and mobile phase for a
            given analyte from the wide variety of chiral columns available requires
            a substantial amount of time and labor. Therefore, there is a demand
            to improve the speed of condition scouting for chiral separations.
            The speed and labor required for scouting chiral compound separation
            conditions can be improved by combining Shimadzu's Nexera UC chiral
            screening  system  and  the  wide  range  of  polysaccharide  derivative
            CHIRALPAK and CHIRALCEL series chiral columns (Daicel Corporation).
            The Nexera UC chiral screening system includes an SFC system, solvent
            switching valves, and column switching valves and is able to acquire
            comprehensive  data  by  automatic  and  continuous  screening  of  the   Fig. 11  Configuration Window of Method Scouting Solution Software
            modifier conditions on a maximum of 12 columns. Its mobile phase
            blending function can also mix up to four different solvents to user-de-  Column  Modi er
            fined ratios for analysis under a variety of separation conditions, which   (1) CHIRALPAK IA-3/SFC  (1) MeOH
            significantly  simplifies  the  workflow  of  condition  scouting  for  chiral   (2) CHIRALPAK IB-3/SFC  (2) EtOH
            compounds.                                            (3) CHIRALPAK IC-3/SFC  (3) Acetonitrile/EtOH 75/25 (V/V)
                                                                  (4) CHIRALPAK ID-3/SFC
            Also, Method Scouting Solution for Nexera UC is software that pres-  (5) CHIRALPAK IE-3/SFC  Modiÿer conc   :  20 %
                                                                                             Flow rate
                                                                                                     :  3.0 mL/min
            ents a graphical user interface environment developed to support the   (6) CHIRALPAK IF-3/SFC  Temperature   :  40°C
                                                                                                     :  10 MPa
                                                                                             Back pressure
            process of separation condition scouting for chiral compounds (Fig.   (7) CHIRALPAK AD-3/SFC  Injection volume  :  1 µL
            11). This software provides database management for analytical col-  (8) CHIRALPAK AS-3/SFC  Detection   :  UV (300 nm)
                                                                  (9) CHIRALPAK AY-3/SFC
            umns, mobile phases, and modifiers, which improves management ef-  (10) CHIRALCEL OD-3/SFC
            ficiency and can reduce the number of operating errors that arise with   (11) CHIRALCEL OJ-3/SFC
            multiple operators. The software provides powerful support for work   (12) CHIRALCEL OZ-3/SFC
            related to chiral compound analysis, including work such as the calcu-  3.0 mm I.D. × 100 mm L. 3 µm
            lation  of  required  modifier  and  sample  volumes,  column  washing,
            changeover of enclosed liquids at                                 Fig. 12  Screening Conditions
            the  end  of  analysis  to  prevent
            column degradation, and estima-        Modi er: MeOH                    Modi er: ACN/EtOH = 75/25 (v/v)
            tion of analysis completion times.  IA     IB      IC      ID           IA       IB      IC      ID
            Here, we present chiral separation
            screening  results  for  omeprazole   IE   IF      AD      AS           IE       IF     AD       AS
            obtained from all 36 possible com-
            binations of the 12 chiral columns
            (Daicel  Corporation)  and  three   AY    OD       OJ      OZ           AY      OD       OJ      OZ
            modifier conditions (Fig. 12, 13).
            The  Nexera  UC  chiral  screening      Modi er: EtOH
            system  utilizes  SFC  to  select  the                                 mAU
                                              IA       IB      IC      ID
            mobile  phase  and  optimize  the                                       CHIRALCEL OZ-3/SFC
                                                                                    MeOH
            separation  conditions  in  a  short                                 600
            time period, which improves R&D    IE      IF      AD      AS        400         Resolution: 7.97
            efficiency during the drug discov-
            ery stage of pharmaceutical pro-                                     200
            duction.                          AY      OD       OJ      OZ
                                                                                  0
                                                                                  0.0  1.0  2.0  3.0  4.0  min
                                                                   Fig. 13  Screening Results
            CHIRALPAK and CHIRALCEL are registered trademarks of Daicel Corporation.


                                                                                                  First Edition: September, 2016
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                                                                                                   © Shimadzu Corporation, 2016
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