Table Of ContentSEPARATION SCIENCE AND TECHNOLOGY
VOLUME 14
Areference series edited by
SATINDER AHUJA
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PRACTICAL APPLICATION OF
SUPERCRITICAL FLUID
CHROMATOGRAPHY FOR
PHARMACEUTICAL RESEARCH
AND DEVELOPMENT
VOLUME 14
Edited by
M H
ICHAEL ICKS
AnalyticalResearch&Development,MerckResearchLabs,Rahway,NJ,UnitedStates
P F
AUL ERGUSON
NewModalities&ParenteralDevelopment,PharmaceuticalTechnology&Development,Operations,
AstraZeneca,Macclesfield,UnitedKingdom
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Dedication
Forthe twoconstants inmylife, Isobel andEmily,withoutwho’s patience and support thisbook
would not have been possible
Paul Ferguson, November 2022
Formyfamily,Thomas,Brendan,Georgina,andKathy,forinspiringmeandformycolleaguesfor
sharing this journeywith me
MichaelHicks, November 2022
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Contents
Contributors xi Otheroperatingparameters:Temperature,pressure
andflowrate 64
Preface xiii
Predictingretentionandselectivity 65
Summary 66
1. Evolution of packed column SFC
References 66
as a greener analytical tool for
pharmaceutical analysis 4. Measurements of drugs and metabolites
in biological matrices using SFC
SusanOlesikandRaffealBennett
and SFE-SFC-MS
Discoveryofsupercriticalfluidsanditsrelevanceto
BradyW.Drennan,A.PaigeWicker,BlairK.Berger,
analyticalseparationscience 1
andKevinA.Schug
Sustainableaspectsofsubcriticalandsupercritical
chromatographicseparationmethods 9 Introductiontodrugandmetaboliteanalysis
AnalyticalscalesubcriticalSFC 10 inbiologicalmatricesusingSFCand
Analyticalenhanced-fluidityliquid SFE-SFC-MS 73
chromatography 12 On-lineSFE-SFC-MSmethoddevelopmentfor
Preparativeandanalyticalscaleinstrument biologicalmatrices 75
improvements 13 Drugmetabolismandpharmacokinetics(DMPK)
Currentutilityandrecentadvancements 20 monitoringindiscoveryanddevelopment 88
Futuredirections 22 Discoveryanddereplicationofnaturalproducts 93
References 22 Conclusions 94
References 94
2. Application space for SFC in
5. Synthetic chemistry screening for robust
pharmaceutical drug discovery
analysis and purification from discovery
and development
through to development
GioacchinoLucaLosacco,AmandineDispas,Jean-LucVeuthey,
TimUnderwood,SeanHindley,AndyKnaggs,andCraigWhite
andDavyGuillarme
Introduction 101
Introduction 29
Screeningstrategies 103
Discussion 33
Practicality 119
ConsiderationsonSFCasananalyticaltoolindrug
Aspectsforconsideration 123
discoveryanddevelopment 38
Futurerefinements 128
Conclusionsandperspectives 42
References 129
References 43
6. Application of preparative SFC in the
3. Selection of SFC stationary
pharmaceutical industry
and mobile phases
JenniferKingston,HannaLeek,AstridBuica,KristinaO€hl(cid:2)en,
CarolineWestandEricLesellier KatieProctor,JoannaRaubo,MatthewSanders,andLindaThunberg
Introduction 49 IntroductiontotheuseofpreparativeSFC 133
CurrentstationaryphasechemistriesforSFC 49 PreparativeSFCinstrumentationand
Flexiblemobilephasecomposition 59 infrastructure 134
vii
viii
Contents
FeaturesandcontrolsduringpreparativeSFC 138 RoleofwaterinmodernSFC 261
Temperaturecontrol 143 Enhanced-fluidityliquidchromatography 269
Detectionsystems 143 ApplicationsofSFCtobiomolecules 279
Fractioncollection 144 Concludingremarks 290
MethoddevelopmentinpreparativeSFC 145 References 290
PreparativeSFCapplications:Casestudieswithin
AstraZenecaresearchlaboratories 148 10. Different detectors used with SFC
SFCasasustainablechromatographictechnique 159
G.JohnLangley,SergioCancho-Gonzalez,
Conclusions 163
andJulieM.Herniman
References 163
Introductiontodetectorsusedwith
7. Method development approaches modernSFC 299
for small-molecule analytes GenericdetectorsusedwithSFC 300
CouplingSFCtomassspectrometric
SyameKhater,PaulFerguson,
detectors 313
andAlexandreGrand-Guillaume-Perrenoud
Conclusions 321
Introduction 167 Acknowledgment 321
Methoddevelopment“prework” 170 References 321
ScreeningtoolutilizationtoidentifyoptimalSFC
parameters 174 11. SFC in GMP testing and quality
Methodvalidation 205 control of medicinal drug products
Continuousmethodperformanceverification 210
Summary 211 AdrianClarke,PaulFerguson,andMichaelHicks
Acknowledgments 212
Introduction 325
References 212
CurrentuseofSFCinpharmaceutical
development 327
8. Application of SFC for the
TransferofmethodstomanufacturingQC
characterization of formulated
facilities 332
drug products Futurerequirementstowardregulatoryacceptanceof
SFCmethods 344
PaulFerguson,RebeccaCross,andGesaSchad
Conclusions 348
Introduction 221 Acknowledgments 348
Drugformulations 222 References 348
Samplepreparationprocedures 225
Waterandorganicsolventsassamplediluentsin 12. Best practices and instrumental
SFCforAPIsandsolid-oraldosageforms 230 troubleshooting for successful
AlternativeapproachestosolubilizeanalytesinSFC SFC methods
compatiblesolvents 237
Characterizationofpolymerexcipients 241 FionaBell,PaulFerguson,RebeccaPoulten,EmilyRoddy,
andWilliamFarrell
Conclusions 246
Acknowledgments 247 Introduction 353
Appendix:Constituentsofformulateddrugsdiscussed
Systemconfiguration 354
inchapter 247
Bestpracticeforsystemsetup 356
References 252
Systemperformancechecks 357
Cylinderissues 361
9. Expanding the boundaries of SFC:
Instrumenttroubleshootinganderrors 364
Analysis of biomolecules Eluenteffects 369
Chromatographictroubleshooting 371
MartinBeres
Optimizationofdetectorsensitivity 374
Historicalproblemsanalyzingpolarmoleculesvia Conclusions 374
SFC 257 References 375
ix
Contents
13. The state-of-the-art and future Methoddevelopment,performanceandprediction
perspectives for SFC aspects 386
Methodscaling 390
PaulFergusonandMichaelHicks FuturedirectionsandapplicationsofSFC 392
Sustainableinstrumentdesign 394
Introduction 377
Conclusions 397
Reflectiononpreviouschapters 378
Acknowledgments 398
TheoreticalperformanceofSFC 382
References 398
Influenceofnewcolumnparticletechnologiesand
instrumentdesignonSFCperformance 383
List of abbreviations 403
Considerationsforfutureinstrumentapplicationand
design 384 Index 409
