The HPLC-MS Handbook for Practitioners

233 Pages·2017·7.294 MB·English

by  Stavros Kromidas

Editedby
StavrosKromidas
TheHPLC-MSHandbook
forPractitioners
Editedby
StavrosKromidas
The HPLC-MS Handbook for Practitioners
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V
Contents
Preface XI
TheStructureofHPLC-MSforPractitioners XIII
ListofContributors XV
PartI Overview,Pitfalls,Hardware-Requirements 1
1 StateoftheArtintheLC/MS 3
O.Schmitz
1.1 Introduction 3
1.2 IonizationMethodsatAtmosphericPressure 5
1.2.1 OverviewofAPIMethods 6
1.2.2 ESI 6
1.2.3 APCI 8
1.2.4 APPI 9
1.2.5 APLI 10
1.2.6 DeterminationofIonSuppression 11
1.2.7 BestIonizationforEachQuestion 11
1.3 MassAnalyzer 12
1.4 FutureDevelopments 13
1.5 WhatShouldYouLookforWhenBuyingaMassSpectrometer? 14
References 15
2 TechnicalAspectsandPitfallsofLC/MSHyphenation 19
M.M.Martin
2.1 InstrumentalRequirementsforLC/MSAnalysis–Configuringthe
RightSystemforYourAnalyticalChallenge 20
2.1.1 (U)HPLCandMassSpectrometry–NotJustaMereFront-End 20
2.1.2 UHPLCSystemOptimization–GradientDelayandExtra-column
Volumes 21
2.1.3 DoesYourMassSpectrometerFitYourPurpose? 33
VI Contents
2.1.4 DataRatesandCycleTimesofModernMassSpectrometers 38
2.1.5 ComplementaryInformationbyAdditionalDetectors
orMassSpectrometryWon’tSavetheWorld 39
2.2 LC/MSMethodDevelopmentandHPLCMethodAdaptation–
HowtoMakeMyLCFitforMS? 43
2.2.1 MethodDevelopmentLC/MS–LCFitstheMSPurposes 44
2.2.2 ConvertingClassicalHPLCMethodsintoLC/MS 53
2.3 PitfallsandErrorSources–SometimesThingsDoGoWrong 54
2.3.1 NoSignalatAll 54
2.3.2 InappropriateIonSourceSettingsandTheirImpact
ontheChromatogram 56
2.3.3 IonSuppression 58
2.3.4 UnknownMassSignalsintheMassSpectrum 59
2.3.5 InstrumentalReasonsfortheMisinterpretationofMassSpectra 65
2.4 Conclusion 68
2.5 Abbreviations 69
References 70
3 AspectsoftheDevelopmentofMethodsinLC/MSCoupling 73
T. Teutenberg, T. Hetzel, C. Portner, S. Wiese, C. vom Eyser, and
J.Tuerk
3.1 Introduction 73
3.2 FromTargettoScreeningAnalysis 74
3.2.1 TargetAnalysis 74
3.2.2 Suspected-TargetScreening 74
3.2.3 Non-targetScreening 74
3.2.4 ComparableOverviewoftheDifferentAcquisitionModes 75
3.3 TheOptimizationofParametersinChromatographyandMass
Spectrometry 75
3.3.1 RequirementsandRecommendationsforHPLC/MSAnalysisTaking
DIN38407-47asanExample 75
3.3.2 TheDefinitionofCriticalPeakPairsintheContextofHPLC/MS
Coupling 77
3.3.3 TheSeparationofPolarComponentsfromtheColumnVoidTime 79
3.3.4 DeterminingtheHPLCMethodParametersUsingtheExample
oftheSeparationofSelectedPharmaceuticals 80
3.3.5 CarryingoutScreeningExperiments 84
3.3.6 EvaluationoftheDataandDiscussionoftheInfluencing
Parameters 86
3.3.7 UsingSimulationSoftwareforFineOptimization 98
3.3.8 ChoosingtheStationaryPhaseSupport 99
3.3.9 TheInfluenceoftheInnerColumnDiameterandtheMobilePhase
FlowRate 103
3.3.10 TheInfluenceoftheInjectionVolume 104
3.3.11 EstablishingtheMassSpectrometricParameters 115
Contents VII
3.3.12 OptimizationoftheMassSpectrometricParameters 117
3.3.13 QuantificationUsingLC/MS 122
3.3.14 ScreeningUsingLC/MS 128
3.3.15 Miniaturization–LC/MSQuoVadis? 132
References 135
PartII Tips,Examples,Trends 139
4 LC/MSforEverybody/forEverything?–LC/MSTips 141
F.Mandel
4.1 Introduction 141
4.2 TipNumber1 142
4.2.1 ChoosingtheRightLC/MSInterface 142
4.3 TipNumber2 148
4.3.1 WhichMobilePhasesAreCompatiblewithLC/MS? 148
4.4 TipNumber3 149
4.4.1 PhosphateBuffer–TheException 149
4.5 TipNumber4 150
4.5.1 PairedIons 150
4.5.2 Which“Antidote”IsAvailable? 151
4.5.3 Summary 152
4.6 TipNumber5 152
4.6.1 UsingAdditivestoEnhanceElectrosprayIonization 152
4.6.2 AdditivesforAPCI 153
4.6.3 Summary 154
4.7 TipNumber6 154
4.7.1 HowCanIEnhanceSensitivityofDetection? 154
4.8 TipNumber7 155
4.8.1 NoLinearResponseandPoorDynamicRange? 155
4.8.2 TheReasons 156
4.8.3 PossibleSolutions 156
4.8.4 Summary 157
4.9 TipNumber8 157
4.9.1 HowMuchMSnDoINeed? 157
4.9.2 Solutions 158
4.9.3 Summary 158
4.10 NeedMoreHelp? 166
References 167
VIII Contents
PartIII UserReports 169
5 LCCoupledtoMS–aUserReport 171
A.MullerandA.Hofmann
References 176
6 ProblemSolvingwithHPLC/MS–aPracticalViewfromPractitioners 177
E.Fleischer
6.1 IntroductionandScope 177
6.2 CaseExample1 181
6.2.1 InvestigationofMethohexitalImpuritiesandDecomposition
Products 181
6.2.2 SamplePreparation 181
6.3 CaseExample2 183
6.3.1 SeparationofOligomersfromCaprolactam,Multicomponent
SeparationofImpuritiesonaGramScale 183
6.4 CaseExample3 184
6.4.1 PreparationandIsolationofbis-NalbuphinefromNalbuphine 184
6.5 CaseExample4 186
6.5.1 IsolationandElucidationofDopamineImpurities 186
7 LC/MSfromthePerspectiveofaMaintenanceEngineer 189
O.Müller
7.1 IntroductionandHistoricalSummary 189
7.2 SprayTechniques 190
7.3 PassageThroughtheIonPath 191
7.4 TheAnalyzer 191
7.5 Maintenance 193
References 198
PartIV Vendor’sReports 201
8 LC/MS–thePast,Present,andFuture 203
T.L.SheehanandF.Mandel
9 Vendor’sReport–SCIEX 207
D.Schleuder
Contents IX
10 ManufacturerReport–ThermoFisherScientific 213
M.M.Martin
10.1 LiquidChromatographyforLC/MS 214
10.2 MassSpectrometryforLC/MS 215
10.3 IntegratedLC/MSSolutions 217
10.4 Software 217
References 219
AbouttheAuthors 221
Index 227
XI
Preface
LC/MScouplinghasdevelopedfromamethodforexpertsinresearchtoawell-
proventechniqueforusers intheirdailyroutine.Hence,thisbookis dedicated
exclusivelytoLC/MScoupling.
It is our goal to give LC/MS users detailed information in orderto use their
LS/MSapplicationinanoptimalmanner.Colleagueswhohaveauthoredarticles
inmypreviousbookshavethereforerevisedandupdatedtheirarticles.Further-
more,newarticlesfromLC/MSpractitioners were added.Whenwriting those
articles,itwasmostimportanttoustohaveaneyeonpractice,butcompactback-
groundknowledgeisalsogiven.Ihopethattheanalystindevelopmentaswellas
theuserindailyroutinewillfindinspirationandtipsforoptimalusageofLC/MS
coupling.
Myspecial thanksgoestoWolfgang Dreherforhiscritical comments tothis
manuscript, furthermore to my author colleagues,who put downtheir experi-
enceandknowledgeinwritingdespitetheirlimitedtimeresources.Iwouldlike
tothankWILEY-VCHandinparticularReinholdWeberandMartinPreussfor
thegoodandclosecooperation.
Blieskastel,March2017 StavrosKromidas
XIII
TheStructureofHPLC-MSforPractitioners
Thebookcontainstenchaptersthataredividedintofourparts:
∙ 1–3:PartIOverview,Pitfalls,HardwareRequirements
∙ 4:PartIITips,Examples
∙ 5–7:PartIIIUserReports
∙ 8–10:PartIVVendor’sreports,Trends
PartI
InChapter1OliverSchmitzoverviewstheStateoftheartofLC/MScoupling
andopposesdifferentmodes.InChapter2MarkusMartinshowsTechnicalas-
pectsandpitfallsofLC/MShyphenationandprovidespreciseandspecifichints
howLC/MScouplingcansuccessfullybeestablishedindailyroutine.Othertop-
icsofChapter2 aremethoddevelopmentas wellasmethod transfer.Thorsten
Teutenbergandco-authorsprovideagreatmanyofsuggestionsinChapter3(Re-
quirementsofLChardwareforthecouplingofdifferentmassspectrometers),
astoarrangeLC/MScouplingasoptimalaspossible.Amongotherthingscom-
plexsamplesandminiaturizationplayanimportantrole.
PartII
InChapter4FriedrichMandeloffersanumerousofLC/MSTipsaddressingdif-
ferenttopicsofLC/MScoupling.
PartIII
Chapter5containsexamplesandexperiencereportsfromusersandserviceengi-
neers:LC/MScouplingisoftenlinkedtolifescienceandenvironmentalanalysis.
AlbanMullerandAndreasHofmannshowinChapter5aconcreteexampleof
LC/MScouplinginionchromatographyasanunfamiliarapplication.InChap-