Preparative Chromatography. of Fine Chemicals and Pharmaceutical Agents

485 Pages·2005·8.49 MB·English

by  Henner Schmidt-Traub

Editedby
H.Schmidt-Traub
PreparativeChromatography
PreparativeChromatography.EditedbyH.Schmidt-Traub
Copyright©2005WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:3-527-30643-9
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Preparative Chromatography
of Fine Chemicals and
Pharmaceutical Agents
Edited by
Henner Schmidt-Traub
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©2005WILEY-VCHVerlagGmbH&Co.
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Introduction
1 Introduction 1
R.Ditz
1.1 LiquidChromatography–itsHistory 1
1.2 FocusoftheBook 4
1.3 HowtoReadthisBook 6
2 FundamentalsandGeneralTerminology 9
M.Schulte,A.Epping
2.1 PrinciplesofAdsorptionChromatography 9
2.1.1 AdsorptionProcess 10
2.1.2 ChromatographicProcess 12
2.2 BasicEffectsandChromatographicDefinitions 13
2.2.1 ChromatogramsandtheirParameters 13
2.2.2 VoidageandPorosity 15
2.2.3 InfluenceofAdsorptionIsothermsontheChromatogram 18
2.3 FluidDynamics 20
2.3.1 ExtraColumnEffects 21
2.3.2 ColumnFluidDistribution 21
2.3.3 PackingNon-idealities 22
2.3.4 SourcesforNon-idealFluidDistribution 22
2.4 MassTransferPhenomena 23
2.4.1 PrinciplesofMassTransfer 23
2.4.2 EfficiencyofChromatographicSeparations 25
2.4.3 Resolution 28
2.5 EquilibriumThermodynamics 32
2.5.1 DefinitionofIsotherms 32
2.5.2 ModelsofIsotherms 33
2.5.2.1 Single-componentIsotherms 34
2.5.2.2 Multi-componentIsotherms 36
2.5.2.3 IdealAdsorbedSolution(IAS)Theory 37
2.6 ThermodynamicEffectsonMassSeparation 41
2.6.1 MassLoad 41
2.6.2 LinearandNonlinearIsotherms 41
2.6.3 ElutionModes 46
VI Introduction
2.7 PracticalAspectsofParameterDetermination 47
2.7.1 LinearizedChromatography 48
2.7.2 NonlinearChromatography 49
3 Columns,PackingsandStationaryPhases 51
K.K.Unger,C.duFresnevonHohenesche,M.Schulte
3.1 ColumnDesign 51
3.1.1 ColumnHardwareandDimensions 51
3.1.2 ColumnswithParticles(ParticulateColumnBeds) 54
3.1.3 ColumnswithaContinuousBed(MonolithicColumns) 55
3.1.4 ColumnPressureDrop 56
3.1.5 FritDesign 57
3.2 ColumnPackings 62
3.2.1 SurveyofPackingsandStationaryPhases 62
3.2.2 Generic,DesignedandTailoredAdsorbents 63
3.2.2.1 GenericAdsorbents 63
3.2.2.2 TailoredAdsorbents 66
3.2.2.3 DesignedAdsorbents 66
3.2.3 ReversedPhaseSilicas 67
3.2.3.1 SilanisationoftheSilicaSurface 68
3.2.3.2 ReversedPhasePackingswithPolymerCoatings
(TypesofPolymerCoatings) 72
3.2.3.3 Physico-chemicalPropertiesofReversedPhaseSilicas 74
3.2.3.4 ChromatographicCharacterizationofReversedPhaseSilicas 76
3.2.4 Cross-linkedOrganicPolymers 78
3.2.4.1 GeneralAspects 79
3.2.4.2 HydrophobicPolymerStationaryPhases 82
3.2.5 ChiralStationaryPhases 83
3.2.6 PropertiesofPackingsandtheirRelevancetoChromatographicPerfor-
mance 86
3.2.6.1 ChemicalandPhysicalBulkProperties 87
3.3 ColumnPackingTechnology 93
3.3.1 CharacterizationoftheColumnBedStructure 95
3.3.2 AssessmentofColumnPerformance 96
3.4 ColumnTesting 97
3.4.1 TestSystems 97
3.4.2 HydrodynamicPropertiesandColumnEfficiency 98
3.4.3 MassLoadability 99
3.4.4 ComparativeRatingofColumns 100
3.5 ColumnMaintenanceandRegeneration 101
3.5.1 CleaninginPlace(CIP) 101
3.5.2 ConditioningofSilicaSurfaces 103
3.5.3 SanitizationinPlace(SIP) 104
3.5.4 ColumnandAdsorbentStorage 105
Introduction VII
3.6 GuidelinesforChoosingChromatographicColumnsandStationary
Phases 105
4 SelectionofChromatographicSystems 107
W.Wewers,J.Dingenen,M.Schulte,J.Kinkel
4.1 DefinitionoftheTask 110
4.2 PropertiesofChromatographicSystems 114
4.2.1 MobilePhasesforLiquidChromatography 114
4.2.1.1 Stability 117
4.2.1.2 SafetyConcerns 117
4.2.1.3 OperatingConditions 117
4.2.2 AdsorbentandPhaseSystem 120
4.2.2.1 NormalPhaseSystem 121
4.2.2.2 ReversedPhaseChromatography 122
4.3 CriteriaforChoiceofChromatographicSystems 124
4.3.1 ChoiceofPhaseSystemDependentonSolubility 125
4.3.1.1 ImprovingLoadabilityforPoorSolubilities 127
4.3.1.2 DependencyofSolubilityonSamplePurity 129
4.3.1.3 GenericGradientsforFastSeparations 130
4.3.2 CriteriaforChoiceofNPSystems 130
4.3.2.1 PilotTechniqueThin-layerChromatography 131
4.3.2.2 RetentioninNPSystems 131
4.3.2.3 SolventStrengthinLiquid–SolidChromatography 133
4.3.2.4 SelectivityinNPSystems 136
4.3.2.5 MobilePhaseOptimizationbyTLCFollowingthePRISMAModel 136
4.3.2.6 StrategyforanIndustrialPreparativeChromatographyLaboratory 145
4.3.3 CriteriaforChoosingRPSystems 150
4.3.3.1 RetentionandSelectivityinRPSystems 150
4.3.3.2 GradientElutionforSmallamountsofProductonRPMaterials 152
4.3.3.3 RigorousOptimizationforIsocraticRuns 154
4.3.3.4 RigorousOptimizationforGradientRuns 156
4.3.3.5 PracticalRecommendations 160
4.3.4 CriteriaforChoosingCSPSystems 162
4.3.4.1 SuitabilityofPreparativeCSP 162
4.3.4.2 DevelopmentofEnantioselectivity 163
4.3.4.3 OptimizationofSeparationConditions 165
4.3.4.4 PracticalRecommendations 166
4.3.5 ConflictsDuringOptimizationofChromatographicSystems 168
5 ProcessConcepts 173
M.Schulte,K.Wekenborg,W.Wewers
5.1 DesignandOperationofEquipment 173
5.1.1 SolventandSampleDeliverySystem 175
5.1.1.1 HPLCPumps 175
5.1.1.2 GradientFormation 175
VIII Introduction
5.1.1.3 EluentDegassing 176
5.1.1.4 EluentReservoir 176
5.1.1.5 SampleInjection 177
5.1.2 ChromatographicColumn 177
5.1.3 DetectionandSeparationSystem 177
5.1.3.1 Solvent-sensitiveDetectors 181
5.1.3.2 FractionCollection 182
5.2 DiscontinuousProcesses 183
5.2.1 IsocraticOperation 183
5.2.2 Flip-flopChromatography 184
5.2.3 Closed-loopRecyclingChromatography 185
5.2.4 SteadyStateRecyclingChromatography 187
5.2.5 GradientChromatography 188
5.3 ContinuousProcesses 190
5.3.1 ColumnSwitchingChromatography 190
5.3.2 AnnularChromatography 190
5.3.3 MultiportSwitchingValveChromatography(ISEP/CSEP) 191
5.3.4 SimulatedMovingBed(SMB)Chromatography 193
5.3.5 SMBChromatographywithVariableConditions 197
5.3.5.1 VariCol 197
5.3.5.2 PowerFeed 199
5.3.5.3 Partialfeed 199
5.3.5.4 ISMB 200
5.3.5.5 ModiCon 201
5.3.6 GradientSMBChromatography 201
5.3.6.1 Solvent-gradientSMBChromatography 201
5.3.6.2 SupercriticalFluidSMBChromatography 202
5.3.6.3 Temperature-gradientSMBChromatography 203
5.4 Guidelines 204
5.4.1 Scale 204
5.4.2 Rangeofk' 205
5.4.3 NumberofFractions 206
5.4.4 Example1:LabScale;TwoFractions 206
5.4.5 Example2:LabScale;ThreeorMoreFractions 206
5.4.6 Example3:ProductionScale;WideRangeofk' 209
5.4.7 Example4:ProductionScale;TwoMainFractions 210
5.4.8 Example5:ProductionScale;ThreeFractions 211
5.4.9 Example6:ProductionScale;Multi-stageProcess 213
6 ModelingandDeterminationofModelParameters 215
M.Michel,A.Epping,A.Jupke
6.1 Introduction 215
6.2 ModelsforSingleChromatographicColumns 216
6.2.1 ClassesofChromatographicModels 216
6.2.2 DerivationoftheMassBalanceEquations 217
Introduction IX
6.2.2.1 MassBalanceEquations 218
6.2.2.2 ConvectiveTransport 221
6.2.2.3 AxialDispersion 222
6.2.2.4 IntraparticleDiffusion 222
6.2.2.5 MassTransfer 222
6.2.2.6 AdsorptionKinetics 224
6.2.2.7 AdsorptionEquilibrium 224
6.2.3 IdealEquilibriumModel 226
6.2.4 ModelswithOneBand-broadeningEffect 229
6.2.4.1 EquilibriumDispersiveModel 230
6.2.4.2 TransportModel 232
6.2.4.3 ReactionModel 233
6.2.5 LumpedRateModels 233
6.2.5.1 TransportDispersiveModel 234
6.2.5.2 ReactionDispersiveModel 235
6.2.6 GeneralRateModels 235
6.2.7 InitialandBoundaryConditionsoftheColumn 238
6.2.8 StageModels 239
6.2.9 AssessmentofDifferentModelApproaches 240
6.2.10 DimensionlessModelEquations 242
6.3 ModelingHPLCPlants 244
6.3.1 ExperimentalSet-upandSimulationFlowsheet 244
6.3.2 ModelingExtraColumnEquipment 246
6.3.2.1 InjectionSystem 246
6.3.2.2 Piping 246
6.3.2.3 Detector 246
6.4 Numericalmethods 247
6.4.1 GeneralSolutionProcedure 247
6.4.2 Discretization 248
6.5 ParameterDetermination 251
6.5.1 ParameterClassesforChromatographicSeparations 251
6.5.1.1 DesignParameters 251
6.5.1.2 OperatingParameters 252
6.5.1.3 ModelParameters 252
6.5.2 DeterminationofModelParameters 253
6.5.3 EvaluationofChromatograms 255
6.5.3.1 MomentAnalysisandHETPPlot 257
6.5.3.2 ParameterEstimation 263
6.5.3.3 PeakFittingFunctions 265
6.5.4 DetectorCalibration 268
6.5.5 PlantParameters 269
6.5.6 DeterminationofPackingParameters 271
6.5.6.1 VoidFractionandPorosityofthePacking 271
6.5.6.2 AxialDispersion 271
6.5.6.3 PressureDrop 273