lc-ms液质联用资料系列

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1、Massspectrometryforthechromatographer••••••LC/MSinDrugDevelopmentIdentifyunknownpeakstosupportmethoddevelopmentandvalidationCharacterizedegradationproductsinforceddegradationstudiesandstabilitysamplesElucidatedrugdegradationpathwaytosupportexcipientselectionandformulationdevelopme

2、ntConfirmpeakidentityforDSandrelatedsubstancesSupportQAissuesandNDASupportManufacturingprocessandfinisheddrugproductsFeaturesofLC/MSAdvantages:•Highsensitivity•Highselectivity•Speed•Combinedpowerofseparationandidentification•MolecularweightandstructureinformationDisadvantages:•Som

3、ecompoundsarenotionizable•Difficulttoidentifycompleteunknowns•LimitedstructureinformationcomparedtoNMRIdentificationStrategy:WhenyoustartLC/MSanalysis…..•IsthemethodMScompatible?•Conditionswheredegradationcompoundsform•Syntheticscheme(Byproduct?Intermediate?)•Structureofdrugsubsta

4、nceactivesitesandfunctionalgroupsNumberofnitrogenatoms,Isotoperatio•FullMSspectrumofunknown:Whichis[M+H]?•MS/MSspectraofDSandunknown•UVspectraofDSandunknownLC/MSAnalysisWorkRequestLC/MScompatiblemethodConfirmChromatogramSelectIonizationModeESIvsAPCI,(+)vs(-)LC/MSincompatiblemethod

5、ModifyHPLCconditionsShowPeakEquivalencyDetermineMWMS/MS(n)StudyIsolation/PurificationProposedStructureNMRConfirmationReportNoConfirmation?YesIn-houseSynthesisLC-MSLCInterfaceExtractionofIonevaporationMassAnalyzerDetectorTheanalytefromorionization.ThesolventFragmentationLC–Separati

6、onofthemixtureofanalytesInterface–SeparationoftheanalytefromthesolventMA(massanalyzer)–separationoftheanalytemolecularionandfragmentsaccordingtotheirmasstochargeratioInfusionMSMicroTeeMSLC100μl/minpump1μl/minSamplesolution•Sampleincontinuousflow•Nosampleinjection•NoLCseparation•MS

7、spectrumobtainedoverangiventime•ImprovedS/Nduetotheaverageofmultiplespectra•SelectLCflowtoassistionization-4BasicElectrospraySchematicN760Torr1Torr10-2–10-5Torr10-5TorrIonopticsFormationofgasphaseionsfromsolutionphaseRichardB.Cole,ElectrosprayIonizationMassSpectrometry,Fundamental

8、sInstrumentationandApplications,W