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The Chiral Notebook Multiple Solutions for Chiral Applications

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The Chiral Notebook Multiple Solutions for Chiral Applications The Chiral Notebook Multiple Solutions for Chiral Applications You’ll find expert advice on: • Novel Chiral Column Screening Approach • Chiral Method Development Tips • Leveraging Easy Column Scale-up • Chiral Resources © 2014 Phenomenex, Inc. All rights reserved. 2 Phenomenex l WEB: www.phenomenex.com Table of Contents Method Development Strategies Alternative Selectivity of Lux® Cellulose-1 and Cellulose-2 [TN-1047] ................................................................. 4 Method Development for RP LC/MS/MS on all 5 Lux Phases [TN-1079] .......................................................... 12 Lux Cellulose-1 Versus Immobilized CHIRALPAK® IB® [TN-1128]...................................................................... 20 Chiral Separation of FMOC Amino Acids by RP Mode [TN-1148] ..................................................................... 26 Novel Screening Approach for the Separation of Pharmaceutical Compounds in SFC Mode [TN-9003] ......... 30 Purification Techniques Purification of Chiral APIs using Axial Compressed Columns [TN-1056] ........................................................... 34 SFC and HPLC Chiral Purification on Lux Axia™ [TN-9001] ............................................................................... 39 Axia Technology vs. Standard Hardware by HPLC and SFC [TN-9002] ............................................................. 43 Pharmaceutical Drugs Applications Separation of Generic PPIs in RP Mode [TN-1102] ............................................................................................ 51 Beta Blockers in NP, RP, and PO Modes [TN-1142] ........................................................................................... 54 Anti-Allergic Agents in NP, RP, and PO Modes [TN-1143] .................................................................................. 58 Pain Relievers in NP, RP, and PO Modes [TN-1144] ........................................................................................... 62 Vasodilator Drugs in NP, RP, and PO Modes [TN-1145] ..................................................................................... 66 Anti-Anxiety and Antidepressive Drugs in NP, RP, and PO Modes [TN-1146] .................................................... 70 Antifungal Drugs in NP, RP, and PO Modes [TN-1147] ....................................................................................... 74 Clinical Drugs Applications Synthetic Cannabinoids Metabolites [TN-1167] ................................................................................................. 78 Pesticide Applications Enantioseparation of Racemic Herbicides [TN-1162] ......................................................................................... 82 Enantiomeric and Diastereoisomeric Resolutions of Chiral Triazole Fungicides [TN-1164] ............................... 86 Preparative Columns Axia: Award-Winning Column Packing Technology ............................................................................................ 92 Guard Columns SecurityGuard™ Extends Column Lifetime .......................................................................................................... 94 Free Chiral Resources Easily Search Over 2,000 Chiral Applications, Method Development Posters, and More ................................. 95 Ordering Information ............................................................................................................. 96 Phenomenex l WEB: www.phenomenex.com 3 TN-1047 APPLICATIONS Alternative Selectivity of Chiral Stationary Phases Based on Cellulose tris(3-chloro-4-methylphenylcarbamate) and Cellulose tris(3,5-dimethylphenylcarbamate Liming Peng, Tivadar Farkas and Swapna Jayapalan Phenomenex, Inc., 411 Madrid Ave., Torrance, CA 90501 USA Introduction HPLC Conditions Polysaccharide-based chiral stationary phases (CSP) are widely Instrumentation used due to their wide chiral recognition ability. Several cellulose Agilent 1100 series (www.agilent.com) and amylose derivatives are extremely effective in the separation HPLC System: of a wide range of compounds of interest in the pharmaceutical Pump: G1311A Quaternary Pump industry1. This work demonstrates the different chiral recognition Autosampler: G1313A ALS capabilities of CSPs based on cellulose tris(3-chloro-4-methyl- Detector: G1315A Diode Array Detector phenylcarbamate) and cellulose tris(3,5-dimethylphenylcarba- mate). Over 180 racemates of pharmaceutical interest were an- HPLC Conditions alyzed on these two phases in normal (NP), polar-organic (PO) Flow Rate: 1.0 mL/min and reversed phase (RP) separation modes. Numerous examples Injection Volume: 5 - 20 μL (depending on analyte response) including important classes of drug compounds as well as statis- Sample tical data prove that cellulose tris(3-chloro-4 methylphenylcarba- 500 μg/mL racemate dissolved in mobile phase mate) offers a good alternative to the commonly used cellulose Concentration: tris(3,5-dimethylphenylcarbamate) in the separation of difficult Columns: Lux® 5 μm Cellulose-1; 250 x 4.6 mm Lux 5 μm Cellulose-2; 250 x 4.6 mm racemic mixtures. CHIRALCEL® 5 μm OD-H®; 250 x 4.6 mm Temperature: Ambient Figure 1. Detector: UV @ 220 nm Structures of Chiral Selective Phases ® Lux Cellulose-1 Table 1. Cellulose tris(3,5-dimethylphenylcarbamate) Mobile Phase Compositions Mobile Phase NP PO Basic and 0.1 % DEA 0.1 % DEA 0.1 % DEA Neutral in Hexane:IPA in MeOH:IPA in CH3CN:IPA Compounds Acidic and 0.1 % HAC 0.1 % HAC 0.1 % HAC Neutral (or FA) in (or FA) in (or FA) in Compounds Hexane:IPA MeOH:IPA CH3CN:IPA IPA: Iso-propanol; DEA: Diethylamine; HAC: Acetic Acid; FA: Formic acid; MeOH: Metha- nol; CH3CN: Acetonitrile Lux® Cellulose-2 Cellulose tris(3-chloro-4-methyl-dimethylphenylcarbamate) 4 Phenomenex l WEB: www.phenomenex.com TN-1047 APPLICATIONS Figure 2. Oxprenolol on Lux Cellulose-1 Enantioseparations of ß-Blockers in Normal Phase 0.1 % DEA in Hexane / 0.1 % DEA in IPA (90:10) mAU Toliprolol on Lux Cellulose-1 0.1 % DEA in Hexane / 0.1 % DEA in IPA (80:20) 400 mAU 400 200 App ID 17481 200 0 0 4 8 min App ID 17478 Oxprenolol on Lux Cellulose-2 0 0.1 % DEA in Hexane / 0.1 % DEA in IPA (90:10) 0 10 20 min mAU 400 Toliprolol on Lux Cellulose-2 0.1 % DEA in Hexane / 0.1 % DEA in IPA (80:20) 200 mAU 400 App ID 17482 0 0 4 8 min 200 Column: Lux 5 µm Cellulose-1 Lux 5 µm Cellulose-2 Dimensions: 250 x 4.6 mm ID App ID 17479 Part No.: 00G-4459-E0 N 0 O NH 00G-4457-E0 H 0 10 20 min Flow Rate: 1 mL/min OH Detection: UV @ 220 nm Temperature: Ambient Oxprenolol Toliprolol on Lux Cellulose-2 0.1 % DEA in Hexane / 0.1 % DEA in IPA (90:10) mAU Bopindolol on Lux Cellulose-1 400 0.1 % DEA in Hexane / 0.1 % DEA in IPA (90:10) mAU 800 200 400 0 App ID 17480 0 10 20 min App ID 17483 0 0 4 8 min Column: Lux 5 µm Cellulose-1 Lux 5 µm Cellulose-2 Bopindolol on Lux Cellulose-2 Dimensions: 250 x 4.6 mm ID 0.1 % DEA in Hexane / 0.1 % DEA in IPA (90:10) Part No.: 00G-4459-E0 HN 00G-4457-E0 mAU Flow Rate: 1 mL/min Detection: UV @ 220 nm O 800 Temperature: Ambient OH 400 Toliprolol App ID 17484 0 0 4 8 min Column: Lux 5 µm Cellulose-1 Lux 5 µm Cellulose-2 Dimensions: 250 x 4.6 mm ID HN Part No.: 00G-4459-E0 00G-4457-E0 O NH O Flow Rate: 1 mL/min Detection: UV @ 220 nm Temperature: Ambient O Bopindolol Phenomenex l WEB: www.phenomenex.com 5 TN-1047 APPLICATIONS Figure 3. Enantioseparations in Normal Phase Warfarin on Lux Cellulose-1 Sulconazole on Lux Cellulose-1 0.1 % Formic Acid in Hexane / 0.1 % Formic Acid in IPA (60:40) 0.1 % DEA in Hexane / 0.1 % DEA in IPA (60:40) mAU Rs: 7.41 mAU Rs: 2.37 400 40 200 20 App ID 17324 App ID 17311 0 0 0 4 8 min 0 10 20 min Warfarin on Lux Cellulose-2 Sulconazole on Lux Cellulose-2 0.1 % Formic Acid in Hexane / 0.1 % Formic Acid in IPA (60:40) 0.1 % DEA in Hexane / 0.1 % DEA in IPA (60:40) mAU Rs: 3.12 mAU 400 Rs: 5.90 40 200 20 App ID 17312 App ID 17325 0 0 0 4 8 min 0 10 20 min Column: Lux 5 µm Cellulose-1 Lux 5 µm Cellulose-2 Dimensions: 250 x 4.6 mm ID Column: Lux 5 µm Cellulose-1 Part No.: 00G-4459-E0 Lux 5 µm Cellulose-2 00G-4457-E0 Dimensions: 250 x 4.6 mm ID Flow Rate: 1 mL/min Part No.: 00G-4459-E0 Detection: UV @ 220 nm 00G-4457-E0 Temperature: Ambient Flow Rate: 1 mL/min Detection: UV @ 220 nm Temperature: Ambient Warfarin on CHIRALCEL®† OD-H® Sulconazole on CHIRALCEL®† OD-H® 0.1 % Formic Acid in Hexane / 0.1 % Formic Acid in IPA (60:40) 0.1 % DEA in Hexane / 0.1 % DEA in IPA (60:40) mAU Rs: 4.40 mAU Rs: 2.19 400 40 200 20 App ID 17313 App ID 17326 0 0 0 4 8 min 0 10 20 min Cl Cl Column: CHIRALCEL® 5 µm OD-H® Column: CHIRALCEL® 5 µm OD-H® Dimensions: 250 x 4.6 mm ID Dimensions: 250 x 4.6 mm ID Flow Rate: 1 mL/min N Flow Rate: 1 mL/min O N Detection: UV @ 220 nm S Detection: UV @ 220 nm Temperature: Ambient Temperature: Ambient O O HO Warfarin Cl Sulconazole *with 0.1 % Formic Acid †CHIRALCEL and OD-H are registered trademarks of DAICEL Chemical Industries, Ltd. Comparative separations may not be representative of all applications. 6 Phenomenex l WEB: www.phenomenex.com TN-1047 APPLICATIONS Figure 4. Complementary Enantioselectivity in Normal Phase and Polar-Organic Sulconazole on Lux Cellulose-2 Milnacipran on Lux Cellulose-2 0.1 % DEA in Hexane / 0.1 % DEA in IPA (60:40) 0.1 % DEA in Hexane / 0.1 % DEA in IPA (80:20 ) mAU Rs: 5.80 mAU Rs: 1.12 40 1200 1000 800 20 600 400 App ID 17325 200 App ID 17489 0 0 0 10 20 min 0 4 8 12 min Sulconazole on Lux Cellulose-2 Milnacipran on Lux Cellulose-2 0.1 % DEA in MeOH / 0.1 % DEA in IPA (95:5) 0.1 % DEA in MeOH / 0.1 % DEA in IPA (90:10) mAU mAU
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