06/09/2015 MSACL 2015 EU Program

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MSACL 2015 EU: Preliminary Conference ProgramSalzburg Congress Center, AUSTRIA • September 8­11, 2015

With Thanks to Our Corporate Sponsors:

TUESDAY

9:00 AM10:00 AM

WELCOME COFFEE@ Mozart 1­3

Enjoy coffee, a muffin and a chat with colleagues before the day starts.

10:00AM

12:00 PMSHORT COURSES: SESSION 1

Getting Started with Quantitative LC­MS/MS in the Diagnostic Laboratory Judy Stone, PhD & Grace van der GugtenLevel: 1­2 (Beginner ­ Intermediate)Location: Mozart 4

Breaking up with Excel: A Newbie's Introduction to the R Statistical Programming Language Daniel Holmes, MD & Stephen Master, MD PhD Level: 1­2 (Beginner ­ Intermediate)Location: Mozart 5

Practical LC­MS Maintenance and Troubleshooting (Tuesday) Erik J. Soderblom, PhD, Christopher Shuford, PhD, J. Will Thompson, PhDLevel: 2 (Intermediate)Location: Trakl Hall Registration for either day of this course (Tuesday or Wednesday) allows you to attend both days.

Development and Validation of Quantitative LC­MS/MS Assays for Use in Clinical Diagnostics Russell Grant, PhD & Brian RappoldLevel: 3 (Advanced)Location: Papageno Hall

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12:00 PM1:00 PM

LUNCH@ Mozart 1­3

Lunch to be provided in Mozart 1­3 with the possibility to eat outside in front of the Congress Center on bistro tables,weather permitting.

1:00 PM3:00 PM SHORT COURSES: SESSION 2

3:00 PM3:30 PM

COFFEE BREAK@ Mozart 1­3

Take a break and get a coffee, water and/or snack. Commune with colleagues or perhaps go for a short walk outside torefresh for the next session.

3:30 PM5:30 PM SHORT COURSES: SESSION 3

5:30 PM7:00 PM

WORKING DINNER@ Mozart 1­3

An evening buffet working dinner with appetizers and drinks to allow you time to connect with your instructor andclassmates before the last hour of class for the day!

7:00 PM8:00 PM SHORT COURSES: SESSION 4

8:00 PMYour

Decision

ENJOY THE CITY@ Salzburg Old City

Explore the Old Town of Salzburg.

TUESDAY CLOSED

WEDNESDAY

8:00 AM8:30 AM

WELCOME COFFEE@ Mozart 1­3

Enjoy coffee, a muffin and a chat with colleagues before the day starts.

8:30 AM10:30 AM SHORT COURSES: SESSION 1

Getting Started with Quantitative LC­MS/MS in the Diagnostic Laboratory Continued from Saturday

Judy Stone, PhD & Grace van der GugtenLevel: 1­2 (Beginner ­ Intermediate)Location: Mozart 4

Breaking up with Excel: A Newbie's Introduction to the R Statistical Programming Language Continued from Saturday

Daniel Holmes, MD & Stephen Master, MD PhD Level: 1­2 (Beginner ­ Intermediate)Location: Mozart 5

Detection Of Pathogens By Whole­Cell MALDI­TOF MS And Advanced Proteomics Approaches Jean­Armengaud, PhD, Oliver Pible & Julia Chamot­Rooke, PhDLevel: 1­2 (Beginner ­ Intermediate)Location: Paracelsus Hall

Practical LC­MS Maintenance and Troubleshooting (Wednesday) Erik J. Soderblom, PhD, Christopher Shuford, PhD, J. Will Thompson, PhDLevel: 2 (Intermediate)Location: Trakl Hall Registration for either day of this course (Tuesday or Wednesday) allows you to attend both days.

Development and Validation of Quantitative LC­MS/MS Assays for Use in Clinical Diagnostics Continued from Saturday

Russell Grant, PhD & Brian Rappold

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Level: 3 (Advanced)Location: Papageno Hall

10:30 AM11:00 AM

COFFEE BREAK@ Mozart 1­3

Take a break and get a coffee, water and/or snack. Commune with colleagues or perhaps go for a short walk outside torefresh for the next session.

11:00AM

12:00 PMSHORT COURSES: SESSION 2

12:00 PM1:00 PM

LUNCH@ Mozart 1­3

Lunch to be provided in Mozart 1­3 with the possibility to eat outside in front of the Congress Center on bistro tables,weather permitting.

Fresh air has been reported to assist in reduced lethargy and increased levels of Vitamin D (if accompanied by sunexposure).

1:00 PM3:00 PM SHORT COURSES: SESSION 3

3:00 PM3:30 PM

COFFEE BREAK@ Mozart 1­3

Take a break and get a coffee, water and/or snack. Commune with colleagues or perhaps go for a short walk outside torefresh for the next session. POSTER PRESENTERS: If you are presenting a poster today, it should be placed by the end of

this break.

3:30 PM5:30 PM SHORT COURSES: SESSION 4

5:30 PM8:30 PM

OPENING RECEPTION@ Exhibit Hall / 1st Floor

Enjoy mingling with colleagues and Exhibitors. Take time to explore the Posters, which will be attended from 6:00 ­ 7:00PM. Buffet dinner and drinks to be provided.

6:00 PM7:00 PM

POSTERS@ Exhibit Hall / 1st Floor

ALL Posters Attended from 6:00 ­ 7:00 PM.

8:30 PMYour

Decision

ENJOY THE CITY@ Salzburg Old City

Explore the Old Town of Salzburg.

WEDNESDAY CLOSED

THURSDAY

7:45 AM8:45 AM

PLACE POSTERS@ Exhibit Hall / 1st Floor

Poster presenters for Thursday must have their posters placed by 9 AM.

7:45 AM8:45 AM

WELCOME COFFEE@ Registration Foyer

Enjoy coffee, a muffin and a chat with colleagues before the day starts.

8:00 AM8:40 AM

CORPORATE WORKSHOPS (8:00 ­ 8:40 AM)

Thermo ScientificPapageno Hall

06/09/2015 MSACL 2015 EU Program

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Time Matters. Simplify Workflow RoutinesDr. Bénédicte Duretz, Thermo Fisher Scientific

Pre­Register

Discover four medical devices for general clinical use: Thermo Scientific™ Prelude MD™ HPLC, Thermo Scientific™Prelude LX­4 MD™ HPLC, Thermo Scientific™ Endura MD™ mass spectrometer, and Thermo Scientific™ ClinQuanMD™ Software. Clinical laboratories can use these devices to build their own lab developed tests (LDT). Various examplecompounds and workflows will be used to demonstrate the robustness and time efficiency of these new medical devices. Forin vitro diagnostic use. Not available in all countries.

8:45 AM

WELCOME, INTRODUCTION & ORIENTATION@ Mozart Hall

Welcome to the 2nd Annual European MSACL Congress!

Congress Mobile AppsTwo apps to facilitate contact collection and Scientific Program browsing.

(1) The Mobile Program AppOnline @ https://www.msacl.org/mobile

(2) BadgerScan™ for Contact Lead Collection.

Available on Google Play and the Apple App Store (iTunes).

PLENARY LECTURE SERIES@ Mozart Hall

Chair: Michael Vogeser & Oleg Mayboroda

9:00 AM9:45 AM

Mass Spectrometry as Metrological Anchor in Laboratory Medicine – a Meandering River Linda MR ThienpontGhent UniversityLong Abstract | Biography | Financial Disclosure

Distinguished Contribution AwardeeThe fundament of mass spectrometric (MS) work is the SI base unit “mole”, more in particular,quantitative MS establishes SI­traceability (mol/L) of measurement results. I will discuss theanchors and regulatory surrounding to implement SI­traceability in laboratory medicine. When Ientered this field, I thought my scientific life would be a “fast­flowing river”. However, severalobstacles forced it to meander, e.g., concepts like biological variation, analytical performancegoals, commutability, and the introduction of MS in routine. Although I tried to cope with theseobstacles, “my river” continues to meander. As an outlook, I will present some of my most recentwork.

9:45 AM10:30 AM

The Cellular Uptake of Pharmaceutical Drugs Is Transporter­Mediated and Is Thus aProblem Not of Biophysics But of Systems BiologyDouglas KellThe University of ManchesterA fundamental question remains as to whether xenobiotic drugs cross cellular membranes mainly(or exclusively) by transporter­independent diffusion across whatever bilayer lipoidal parts ofcellular membranes may be present, or whether they normally (or exclusively) ‘hitchhike’ ridesusing the carriers normally involved in the metabolism of natural metabolites. The former (forwhich, astonishingly, there is in fact no actual experimental evidence) would involve a biophysicalmechanism, based mainly on lipophilicity, while the latter requires a mechanistic understanding ofwhich carriers are involved, and is thus a problem of network or systems biology. In other words,“is carrier­mediated transport of pharmaceutical drugs the exception or the rule?” A huge amountof literature (see Long Abstract), that I shall summarise, indicates that there is no serious evidence

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against the view that trans­phosphobilayer­mediated transfer of pharmaceutical drugs acrossbiological membranes is negligible (‘PBIN’), while there is abundant and increasing evidence forthe carrier­mediated route. A recent approach in yeast illustrates this experimentally, while thedigital availability of principled metabolic network models allows one to determine, consistentwith this, that successful pharmaceutical drugs are much more like metabolites than are the‘Lipinski­compliant’ molecules typically available in drug discovery libraries. This suggests (or isat least consistent with the view) that cellular drug uptake is more or less exclusively transporter­mediated, and that knowledge of both the metabolome and of the concentrations and activities oftransporters used by individual xenobiotics will be of much value in designing better drugs andbioprocesses.

10:30 AM11:15 AM

COFFEE BREAK@ Exhibit Hall / 1st Floor

Visit the Exhibit Hall to procure coffee, juice, water and/or snacks. Explore what's on offer from the Exhibiting vendors,reconnect with colleagues, or go for a short walk outside to refresh for the next session. POSTER PRESENTERS: If youare presenting a poster today your poster should have been up 2 hours ago. If it is not up please put it up immediately.

Sponsored by:

GENERAL SCIENTIFIC SESSION 1

Track 1Mozart 1­3

Small MoleculeAssay DevelopmentChair: Jody van den

Ouweland

Track 2Mozart 4­5Early Life

MetabolomicsChair: Uta Ceglarek

Track 3Papageno Hall

Proteomics AssayDevelopment

Chair: Steve Master

Track 4Paracelsus Hall

DESIChair: David Phelps

Track 5Trakl Hall

Intro to Mass SpecChair: Jane Yang

11:15 AM11:40 AM

Design ofOptimization: Howto SystematicallyImprove thePerformance ofHigh Volume LC­MS/MS ClinicalAssaysBrian RappoldEssential TestingLong AbstractMethod optimizationis largely a colloquialterm for LC/MS/MSusers. The extent ofoptimization canrange from cursoryevaluations duringcore developmentexperiments tosubstantiveinvestigations of allvariables associatedwith a method.Unlike design ofexperimentationwhich requires broadassumptions andlarge experimentalparameter shifts,design ofoptimization relies onefficiently designedexperimentation withthe ability to produce

Diagnosis of InbornMetabolic Disordersvia AbsoluteEnzymatic ActivityZdenek Spacil

University ofWashingtonLong Abstract | BioThe newbornscreening forlysosomal storagedisorders, such assphingolipidoses ormucopolysacharidosesis critical to detectaffected individualsand to timely initiatetreatment. Over 15screening assaysdeveloped in our labmeasure activity oflysosomal enzymes indried blood samples(DBS) by tandemmass spectrometrytechnology (SRM).These assays greatlyoutperform otherscreening tests, suchas fluorometric assaysin terms of sensitivityand specificity, areeasy to implement andallow for

Development ofClinical AssaysBased on ParallelReactionMonitoringBruno DomonLuxembourg ClinicalProteomics CenterLong Abstract | BioTargeted proteomicsanalyses of biomarkerare routinelyperformed on triplequadrupole massspectrometers, whichpresent limitedselectivity, due to lowresolution of the massfilters. The targetedanalyses of clinicalsamples carried outon a quadrupole­orbitrap massspectrometer usingparallel reactionmonitoring (PRM)showed a significantgain in sensitivity andselectivity. A newacquisition methodleveraging thepresence of internalstandards showed adramaticimprovement of the

Ovarian TissueIdentification withRapid EvaporativeIonisation MassSpectrometry(REIMS); theSurgical IntelligentKnifeDavid Phelps

Imperial College,LondonLong Abstract | BioOvarian cancer iscommon and 5­yearsurvival is 43.5%.Surgeons use intra­operative frozensection for tissueidentification but thisis time­consumingand expensive.Microscopic non­descript lesionsduring surgery,which may be cancercan be difficult tocorrectly identify.The near­real­timetissue identificationabilities of the iKnifewere tested in thisstudy. We haveshown for the firsttime that ovarian,

Introduction toMass SpectrometryJane YangUniversity ofCalifornia, SanDiegoLong AbstractMass spectrometry isa powerful analyticalchemistry tool thatdetects molecules inthe gas phase basedon their mass tocharge ratio. Thissession will cover thebasic concepts ofmass spectrometry,how it works, thecomponents of amass spectrum,tandem MS (orMS/MS), therelationship betweenchromatograms andmass spectra, tuning,and what yourservice representativewill do.

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valid conclusions.This paper willintroduce a practicalseries ofexperimentalframeworks toscientificallyrationalize theparameters andprocesses involved inoptimization of aclinical diagnosticsassay. Examples willbe shown fromassays which analyzemore than 500specimen/day.

multiplexing, whichwas collectivelydemonstrated innumerous pilot studiesworldwide. Besidesthe latest developmentand clinical data frompilot studies, we areplanning to present onthe absolute enzymeactivity measurementin highly purifiedleukocyte populationsas a second­tierdiagnostic test, whichis transforming thefield.

reliability and theprecision of theanalyses. The methodhas a broadapplicability to thequantitative analysisof clinical samples,such as lung cancerplasma samples todiscriminate thedisease stages andsubtypes; and totissue samples to mapdriver mutations(EGFR and KRAS).

peritoneal andfallopian tube tissueshave unique REIMSspectral signatures,which can be used toaccurately classifytissue histopathology.Leave­one out patientcross­validationresulted in 100%sensitivity and 100%specificity in theseparation of normaland cancerous ovary(n=189).

11:40 AM12:05 PM

What Is Wrong inYour LC­MSAnalysis? PostColumn Infusion asa Diagnosis ToolOskar Gonzalez

University of theBasque CountryLong Abstract | BioContinuous post­column infusion ofstandards is a veryuseful tool to obtainadditional and veryvaluable informationabout a LC­MSmethod. Here weshow multipleapplications of thistechnique in methoddevelopment androutine analysisbased on ourexperience in thelaboratory: detectionof compoundscausing ionsuppression, aid insample treatmentchoice,understanding ofabnormal results,compensation ofmatrix effect andsome others.Considering all thesebenefits, weencourage to use thistechnique in clinicalanalysis to improvethe reliability of LC­MS methods and toobtain more accurateresults.

Research intoLysosomal StorageMetabolism UsingPlasma LipidCharacterization byLC­MS/MSDan BlakeSCIEXLong Abstract | Bio |Financial DisclosureResearch into plasmasphingolipids anddetermining theconcentrations of suchis of growingimportance in theclinical researchlaboratory,particularly withingroups researchingLysosomal StorageMetabolism. Currentmethods of analysisprimarily involveeither enzyme activityprocedures orderivatization ofcompounds prior toanalysis. Directanalysis of thesegroups can becomplex due toextensive structuralhomogeneity betweenindividualcompounds. Wepresent here a methodfor a direct multi­compound approachto this analysis,employing modernadvances in columntechnology to producea rapid and sensitiveLC­MS/MS methodfor these compounds.

MS­based SerumProteomics inClinical Chemistry:Requirements forCandidateTranslation andImplementation as aRoutine AssayChrista CobbaertLeiden UniversityMedical CenterLong AbstractNumerous serumprotein profilingefforts have aimed forbiomarker discoverysince the early daysof massspectrometry(MS)­based proteomics.These pipelines haveyielded manypromising proteincandidates, butdisappointingly noneof these has beentranslated into a trulyvalidated medicaltest. Alternatively,strategies have beenfollowed to convertexisting routineuniplex proteinassays into an MS­based in­vitrodiagnostic test,however also in thiscase the success ratehas been low so far.In this presentationboth approaches willbe discussed withregard torequirements neededfor translation orimplementation theseinto a clinicalchemistry laboratory.

The MucosalMetabolome: Real­time Rapid MedicalSwab Point­of­careAnalysis UsingTFME­DESI MS toReveal Pathogenicand InflammatoryMetabolomicMarkers Pamela Pruski

Imperial CollegeLondonLong Abstract | BioThe mucosalmembrane, aprotective layerresponsible fortrapping pathogens inthe human body, isan easily accessibleand highly clinicallyrelevant sample todiagnose pathogenicand cancerousassociated diseases.Since DESI MS isnot applicable for in­vivo analysis due tothe potential risk ofelectrical shock andthe use of organicsolvent, medicalswabs are a standardcollection device formucosal membranesthat can be directlyanalysed with DESIMS. Chemicalsignaturesidentification ofspecific bacteriawithin minutes on thesurface of swabswould provide arapid diagnosis ofinfections associated

Introduction toIonization Modes inMass SpectrometryJörg Hanrieder

University ofGothenburgLong AbstractIonization of analytesinto the gas phase is acritical step foraccurate massidentification.Various types ofionization methodscan be applied foroptimal analyteidentification. Thissession will involve abasic introduction tovarious ionizationmodes used in massspectrometry and willdiscuss theadvantages anddisadvantages ofeach.

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with preterm deliveryin comparison tostandard microbialtesting.

12:05 PM12:30 PM

Fully AutomatedMulti­Method LC­MS: Application inClinical LaboratoryMarco CantùEnte OspedalieroCantonaleLong Abstract | BioIn the last 4 years wesetup a flexibleconfiguration able todo differentanalytical methodson a single LCMS.This configuration isable to loadsimultaneously: up to24 solvents into theprimary pump, up to4 solvents into thesecondary pump, upto 15 columns,divided into 2independentthermostats. Thissystem is able tomanage allinstrument’s changes(solvent lineselection, columnselection, etc.)directly from thework­list. This is areal huge result thatopen the possibilityto process urgentsamples just addingthem into the work­list also while theLCMS is processingother methods,without any switchoff, changes andrestart.

Preeclampsia RiskStratification Earlyin Pregnancy: FirstResults of a New LC­MS Based MultiplexMetabolite AssayRobin TuyttenMetabolomicDiagnosticsLong Abstract | Bio |Financial DisclosurePreeclampsia is one ofthe majorcomplications ofpregnancy. First timepregnant women havean increased risk forpreeclampsia, yetroutine prenatal carefails to accuratelyidentify the 1st timepregnant women atrisk. Basic biomarkerresearch revealed thatblood bornemetabolites bearpotential to risk­stratify forpreeclampsia early inpregnancy. In adedicated translationalresearch effort, aprototype multiplexmetabolite LC­MSassay was developedand then applied to alarge case:controlstudy focusing on 1sttime pregnant women.This study confirmedthat the newlydiscovered metabolitebiomarkers enableprediction ofpreeclampsia riskearly in pregnancy.

The Holy Trinity:The Inter­relationship ofStandards, Matrix,and InternalStandardization inProtein CleavageIsotope DilutionMass Spectrometry(PC­IDMS) Russell GrantLaboratoryCorporation ofAmericaLong Abstract | Bio |Financial DisclosureTo better understandthe inter­relationshipof calibration (matrixand standard) andinternalstandardization on theaccuracy ofdigestion­basedproteinquantification, therelative digestionefficiency of multipleinternal standardtypes(peptides/protein),multiple standardizedforms of unlabeledprotein(recombinant/human­derived) and multiplematrices(true/surrogate) areevaluated forquantifyingthyroglobulin inserum using multiplesignature peptides.Comparing multiplematrices and proteinstandards willdifferentiate if thedisparities/similaritiesbetween peptides arematrix effects and/orspecific to theanalytical standardused. A variety ofdigestion conditionsare explored incombination withdifferent internalstandards todetermine ifdisparities betweenpeptides can be

DESI­MS andREIMS as ExcellentTechniques toComplement andSupport Histologyin Ovarian Cancer Luisa DoriaImperial College ofLondonLong Abstract | BioOvarian cancer is thefifth most commoncancer amongwomen and one ofthe causes is the poorand vague prognosisand diagnosis.REIMS and DESI­MS are two massspectrometrytechniques with greatpotential tocharacterize anddiscriminate differentcancer types andstages. Bothtechniques areexcellent tocomplement andsupport histology,REIMS can identifydifferent ovariancancer types in realtime and DESI canprovide detailedspatial informationwithin the samplegiving theopportunity toinvestigate tumourbiology from anentirely newperspective withaccurate biochemicalinformation abouteach tissue type.

Introduction toMass Analyzers:Quadrupole vs.Time­Of­Flight(TOF)Jörg Hanrieder

University ofGothenburgLong AbstractChoosing a massanalyzer for clinicalanalysis is animportant step insetting up a massspectrometrylaboratory. But whatis a mass analyzer?Are all massanalyzers are createdequal? What types ofclinical tests can bevalidated on each?Each type of massanalyzer has its ownbenefits and caveatsin mass resolution,sensitivity, anddynamic range forsmall moleculeanalysis. Choosing amass analyzer to suitthe needs of theclinical laboratory isan importantconsideration tomake. This lecturewill focus onquadruple and timeof flight (TOF) massanalyzers foridentification andquantification ofsmall molecules. Thislecture will alsodescribe how thesedifferent massanalyzers actuallycreate massseparations and willdescribe the variousclinical applicationsavailable to each.

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mitigated.

12:30 PM2:30 PM

LUNCH@ Exhibit Hall / 1st Floor

Lunch to be provided in the Exhibit Hall. • Get ready to join a Corporate Workshop after the poster session.

Sponsored by:

1:30 PM2:30 PM

POSTERS@ Exhibit Hall / 1st Floor

All Posters to be attended from 1:30 ­ 2:30 PM.

2:30 PM3:30 PM

CORPORATE WORKSHOPS (2:30 ­ 3:30 PM)

ShimadzuMozart 1­3

Smart Solutions: FullyAutomated Systems forYour LaboratoryApplicationsPre­Register

1. TDMPREP ­Centrifugation FreeSample Preparation withMagnetic Beads! Mario WUTTKE,Magnamedics, Netherlands

2. New Developments inNBS using DBS forMetabolic Profilingincluding Steroids Prof David C. KASPER,MedUniVienna/ARCHIMEDlife,Austria

3. New LCMS­8060: OpensUp the Way for NewApplications Stephane MOREAU,Shimadzu Europa Gmbh,Germany

4. Fully Automated Systemincluding SamplePreparation Stephane MOREAU,Shimadzu Europa Gmbh,Germany

Thermo ScientificMozart 4­5

Identifying UnknownUnknowns with HighResolution Accurate MassMS in ToxicologyRobert Mistrik, HighChemPre­Register

Despite the increasing use ofmodern high resolution massspectrometers, toxicologicalanalysis is hindered by aninability to identify detectedcompounds effectively. Wewill present an advancedcomputational and databaseframework leading to themuch anticipated increase incoverage of toxicologicallyrelevant compounds andtheir transformationproducts, taking into accountall the importantexperimental and calculatedinformation necessary forefficient and reliableidentifications. Thosemethods are exploitingcombination of librarysearching methods, bothspectral (mzCloud) andstructural (PubChem,ChemSpider), withcomputational techniqueslike quantum chemicalmethods, precursor ionfingerprinting, fragment ionsearch and others.

Agilent TechnologiesPapageno Hall

Workshops onStreamSelect, MetabolicWorkflows and SamplePrep with AssayMAPBravo

1. Introducing the NewAgilent StreamSelectLC/MS SystemPete Christensen, PhD,Agilent Technologies, UK

2. Metabolomic Workflowsfor Clinical Research­demonstrating a tool toaddress investigation ofinborn metabolic errors Dr. Holger Stalz, AgilentTechnologies, Switzerland

3. Rethink your ProteinSample PreparationStrategy with AgilentAssayMAP Bravo Moritz Wagner, PhD,Agilent Technologies,Germany

Spark HollandParacelsus Hall

Scientific andInstrumental Advances inDried Blood Spot AnalysisChristophe Stove and BertOomsDried blood spot analysis isemerging as a useful tool forquantitative bioanalysis,particularly for microvolumes of blood or plasma.DBS enables remotesampling in low resourcesettings or at­home samplingfor out­patients. The micro­volume concept helps toreduce lab­animal use andallows use of finger prickinstead of venous puncture,making the technique easierapplicable for children.However, issues such as theeffect of hematocrit on spotsize have hindered broadacceptance of DBS forroutine bioanalysis. Recentinnovations have addressedthese issues and will bepresented and discussed inthis workshop by professorChristophe Stove (GentUniversity). An introductionto the new DBS autosamplerfrom Spark Holland will bepresented by Bert Ooms,principal scientist(SparkHolland).

3:30 PM4:30 PM

COFFEE BREAK@ Exhibit Hall / 1st Floor

Visit the Exhibit Hall to procure coffee, juice, water and/or snacks. Explore what's on offer from the Exhibiting vendors,reconnect with colleagues, or go for a short walk outside to refresh for the next session.

Sponsored by:

06/09/2015 MSACL 2015 EU Program

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GENERAL SCIENTIFIC SESSION 2

Track 1Mozart 1­3

Small BiomarkersChair: LaurentDecosterd

Track 2Mozart 4­5Steroid

MetabolomicsChair: Roland Geyer

Track 3Papageno HallQuantitativeProteomicsChair: AndyHoofnagle

Track 4Paracelsus Hall

Advanced ClinicalMicrobiologyChair: IreneBurckhardt

Track 5Trakl Hall

Basics of MassSpectrometry

Chair: Steve Master

4:30 PM4:55 PM

EndogenousOuabain – LC­MS/MS Identifies aFictionSilvia BaecherHospital of theUniversity of MunichLong Abstract | Bio |Financial DisclosureFor decadesimmunoassays wereapplied in an attemptto quantify thecardiac glycosideouabain in plasma ofpatients withcardiovascularconditions. Thiscompound (CAS630­60­4) wassupposed to be ofendogenous origin asa counterpart ofexogenous cardiacglycosides such asdigoxin. Using a fullyvalidated, highlyspecific andextremely sensitiveLC­MS/MS methodwe were able to showthat ouabain cannotbe present in relevantconcentrations inhuman plasma ­ asclaimed byimmunoassay studies.

Quantitation ofSteroid Hormones inDifferent BiologicalMatrices – OneMethod to RuleThem AllAlexander Gaudl

Leipzig UniversityLong Abstract | BioThe quantitativeanalysis ofendogenous steroidhormones cuts acrossplasma, serum, saliva,urine, dried blood andhair renderingimmunologicalanalysis laborious dueto the need ofdifferent methods. Wedeveloped a unifying,highly adaptive LC­MS/MS­methodcovering the mostimportant endogenoussteroid hormones.With excellent interday imprecision (315%), very highrecovery (89 103%)and a total runtime of5.0 min we enabledrapid, multi­matrixanalysis utilizingMRM and MS³ inmodified, positive andnegative electrosprayionization. Onlinesample clean­up viaautomatic columnswitching combinedwith an extremelysimple dilute­and­shoot samplepreparation allowshigh throughputanalysis in clinicalroutine diagnosticsand epidemiologicalstudies.

TargetedQuantification of 97Proteins in DriedBlood SpotsChristoph BorchersUVic Genome BCProteomics CentreLong AbstractWe report amultiplexed LC­MRM­MS methodfor the precisequantification of 97endogenous proteinsin human DBSsamples, suitable forbiomedical researchapplications.Standard curves weregenerated for each ofthe 173 targetpeptides(representing the 97proteins) to fullycharacterize theassay’s analyticalmerits. Furthermore,the stability of eachtarget peptide wasinvestigated in DBSsamples stored at­20°C, 4°C, RT and37°C over a durationof 154 days. Finally,we will present asimple strategy formanaging thehematocrit effectacross samples anddiscuss theimplications on theDBS­MRMworkflow.

Automated RapidEvaporativeIonisation MassSpectrometry(REIMS) for theCharacterisationand Identification ofMicrobesFrances BoltImperial CollegeLong Abstract |Financial DisclosureThe introduction ofmass spectrometryfor clinicalmicrobiologylaboratories hasrevolutionised workflows and providedtimely and accurateclinical diagnoses.Rapid evaporativeionisation massspectrometry(REIMS) haspreviously been showto allow thedifferentiation offungi and bacterialspecies based upontheir lipidome(Strittmatter et al.,2013; Strittmatter etal., 2014). In order toutilise this tool forclinical diagnosticsand research we arecreating a spectrallibrary comprisingover 50,000 isolatesand 4000 species. Anovel customisedTECAN platformwhich incorporatesautomated colonyimaging, colonypicking and REIMSanalysis has beendeveloped to providea reproducible systemfor high throughputworkflows. REIMSon the customisedTECAN EVO

Tuning Your MassSpectrometer: Howto Make It SingMichael ChenMcGill UniversityTuning isfundamental tooperating a massspectrometer andinvolves masscalibration and massresolution. Thisoverview will focuson what happenswhen the massspectrometer is tunedand introduces basicchemical concepts tohelp novice usersunderstand what itmeans when yourinstrumentrepresentative says “Ineed to tune the massspectrometer”.

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platform provides anideal method fordifferent applicationsincluding clinicaldiagnostics, lipidomeand metabonomicanalysis.

4:55 PM5:20 PM

Quantitation ofDesmosine inPlasma by LC­MS/MS asBiomarkers forElastin DegradationJody van denOuwelandCanisius­WilhelminaHospitalLong Abstract | BioDesmosine is apromising biomarkerfor estimatingactivity of elastindegradation inpatients with COPD,although its clinicalvalidity remainsuncertain as reliableand sensitive assaysare lacking. An LC­MS/MS method formeasuring plasmadesmosine wasdeveloped andvalidated. Samplepreparation consistedof acid hydrolysis,cellulose SPE usingD4­DES as IS,followed by C18chromatography andMS­analysis usingSRM. Measuringrange was 0.1­10ng/ml, imprecision<10%, withrecoveries within 80­120%. Plasmadesmosine levelsfrom COPD patientswere significantlyhigher compared withhealthy individuals.The LC­MS/MSassay appears avaluable tool toassess the potential ofdesmosine as abiomarker formonitoring diseaseactivity in COPD andto study the effect oftherapeuticinterventions.

Strategy to Identifyand ValidateUrinary SteroidBiomarkersObtained byUntargeted LC­MS/MSMetabolomics:Application toHuman Cases ofDioxin ExposureFabienne JeanneretUniversity of GenevaLong Abstract | BioIn vitro metabolicreactions wereinvestigated toimprove theidentification ratefrom urinarybiomarkers obtainedby untargetedmetabolomicapproaches. Aprevious studyperformed withUHPLC­QTOFhighlighted a subset of24 urinary steroid andbile acid biomarkersin human cases ofacute dioxin exposure.Biosynthesis ofglucuronide andsulfate conjugates ofbiomarker candidates,respectively producedin human livermicrosomes andcytosolic fractions,was demonstrated as asuccessful approach toidentify urinarymetabolites whenauthentic chemicalstandards are notcommerciallyavailable. Analysis ofthe biomarkers subsetin an independenthuman cohort exposedto dioxinsstrengthened thehypothesis ofdysregulated profilesof steroids and bileacids.

Quantification ofHuman ReceptorTyrosine­proteinKinase ErbB­2(HER2) by TargetedMass Spectrometryin Formalin­FixedParaffin­EmbeddedBreast CancerTissueAxel DucretF. Hoffmann­LaRoche LtdLong Abstract | Bio |Financial DisclosureWe describe in thisstudy a selectedreaction monitoring(SRM) assay for thequantification ofHER2 in FFPEtissues. The assay’ssix best candidatepeptides showed alinear response over acalibration range of0.012 to 100 fmol oncolumn (R2: 0.99–1.00) and a lowerlimit of quantificationof 0.155 fmol oncolumn. HER2peptides werequantified in a cohortof 40 breast tumorsexpressing differentHER2 levels (FISHratio: 0­2, 2­4, 4­10and >10respectively). TheSRM assay showedgood analyticalperformance and ahigh agreement withIHC and FISH data.Furthermore, afternormalization fortissue sample size,SRM peptidemeasurements wereable to correctlypredict 90% of HER2amplification statusas defined byAmerican Society ofClinical Oncologyand College ofAmerican

Skin Imprinting inSilica Plates: APotential DiagnosticMethodology forLeprosy UsingHigh­ResolutionMass SpectrometryEstela de OliveiraLimaUniversidadeEstadual deCampinasLong Abstract | BioLeprosy is aninfectious diseasecaused byMycobacteriumleprae, primarilypresent at skinmacrophages andSchwann cells.Presently, theavailable laboratorialdiagnostic methodsfor Leprosy areinvasive, expensive,and present lowsensibility for theasymptomatic cases.Therefore, this workintended to develop anoninvasive, fast andsensible method forleprosy diagnosis,associated to high­resolution massspectrometry. Ourdata analysis haselected twomycobacterialbiomarkers at leprosyskin patients, absentat control samples.These results indicatethat our newmethodology can becandidate as a fastand sensible leprosydiagnostic method,even for patientswithout clinical skinmanifestations.

Varying ThoseVexing Voltages:Compound SpecificTuningDaniel HolmesSt. Paul's Hospital,VancouverAfter ensuring yourinstrument’sresolution and massaccuracy areappropriately set, thenext step indeveloping aquantitative LC­MS/MS multiplereaction monitoring(MRM) assay is toperform compound­specific tuning. Well­defined signal­optimizationexperiments are usedto determineappropriate ionsource electronicsand gas flowparameters tospecifically quantifythe compound ofinterest. Thisoverview willintroduce basicconcepts of so­called"compoundoptimization". Inother words, we willexplain what is meantwhen people say thatthey have "developedmass spectrometricmethod."

06/09/2015 MSACL 2015 EU Program

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Pathologists.

5:20 PM5:45 PM

Assaying ProteinUnbound DrugsUsing a HighlySensitive LC­MS/MS MethodHeike Bittersohl

Klinikum rechts derIsarLong Abstract | BioTherapeuticmonitoring of proteinunbound (free)immunosuppressantshas the potential tobetter predict theclinical outcomecompared toconventionalmonitoring of druglevels in whole bloodor plasma. Only asmall proportion ofdrugs are free in thepatient blood, hence,requiring a sensitiveanalytical method fortheir determination.We established anLC­MS/MS methodable tosimultaneouslymeasure levels ofcyclosporine A andmycophenolic acid inthe picomolar range.This procedure iscurrently applied in astudy on samplesfrom kidneytransplant recipientstaking both drugs as acombination therapy.

Not Always CAH.Urine SteroidProfiling in theInvestigation andDiagnosis of AdrenalCauses of NeonatalHyponatraemia andFailure to ThriveFrancis Lam

UCLH NHSFoundation TrustLong Abstract | BioA baby presented at alocal hospital withfailure to thrive. Initialbiochemistry showedhyponatraemia andhyperkalaemia. Otherblood analyses wereinconclusive. A spoturine sample was sentfor urine steroidprofile (USP)analysis. The USPshowed a relativeabundance ofcorticosteronemetabolites withundetectabletetrahydroaldosterone,a pattern indicative ofaldosterone synthasedeficiency,subsequentlyconfirmed by genetictesting in thislaboratory. Where asteroid disorder issuspected, a USP hasgreat utility since thespecimen is easilyaccessible and canidentify/exclude avariety of disorders.Where urgent samplesare involved, analysescan be prioritised withrelatively rapidturnaround time.

Calculated HbA1cfrom Total GlycatedHemoglobin byQuantitativeMALDI­TOF MassSpectrometryJane YangUCSDLong Abstract |Financial DisclosurePercent HbA1c, thestandard measure ofglycated hemoglobinused to diagnose andmonitor diabetesmellitus, correlateslinearly with totalglycated hemoglobin(tGHb). MALDI­TOF massspectrometry ofwhole bloodhemolysates allowsthe direct quantitationof the total glycatedhemoglobin (tGHb)ratios of alpha andbeta chains from asingle mass spectrum.Sample preparationfor this approach isminimal, analysis israpid, 80 spots in 20min (15 sec/spot),and hemoglobinvariants are alsodetected. tGHb byMALDI isreproducible withintra­plate CVs <1.4%, linear vs.cation exchangeHPLC (y = 1.20x –1.07; R2 = 0.99) from2.7% to 22% A1c.MALDI method isfaster and lessexpensive thanHPLC.

Discrimination andRelativeQuantitation ofClosely RelatedPathogens inComplex ClinicalSamplesOlivier PibleCEALong Abstract | BioMass spectrometry isa powerful tool toidentify pathogens.However some issuessuch as mixturehandling are usuallybeyond reach ofwhole­cell MALDI­TOF approaches. Wedeveloped a tandemmass spectrometryapproach which notonly can addresscomplicated samplessuch as mixtures ofany organisms, butcan also give accessto relativequantitation ofpathogens. It is basedon the analysis of thepeptide content of thesample and theextraction ofphylogeneticinformation. Anuniversal organismsignature has beencharacterized usingthis molecularinformation. Theidentificationproblem is thenreduced to the searchof the linearcombination oforganism signatureswhich best matchesthe overall massspectrometry signal.

Building yourAssay, Breakingyour Compound:Developing MRMTransitionsStephen MasterWeill CornellMedical CollegeNow that youunderstand how toperform compound­specific tuning, youare ready to buildyour assay. In thissession, we willexplore how to take acompound that you'reinterested inmeasuring by massspectrometry, break itapart, and pickappropriate productions for quantitation.This is the final stepthat allows you tosensitively andspecifically measurethe abundance ofyour desired analyte.

5:45 PM7:45 PM

RECEPTION@ Exhibit Hall / 1st Floor

Enjoy mingling with colleagues and Exhibitors. Take time to browse the posters. Buffet dinner, appetizers and drinks to beprovided. POSTER PRESENTERS: Remove posters between 7:30 ­ 7:45 PM.

Sponsored by:

PLENARY LECTURE SERIES@ Mozart Hall

Chair: Russell Grant

06/09/2015 MSACL 2015 EU Program

https://www.msacl.org/2015_EU_program/ 12/20

7:45 PM8:30 PM

Why Patients Adore Mass Spectrometry Andy HoofnagleUniversity of WashingtonPhysicians rely on high quality measurements of small molecules and proteins for the diagnosis,prognosis, and management of disease. Health care providers have become reliant on relativelyinexpensive, high­throughput immunoassays to capture biomarker data from patient samples.Unfortunately, these assays can be misleading. Clinical mass spectrometric assays bring sensitivityand specificity together in previously unthinkable ways and span the range of medical specialties.This talk will describe the ways in which mass spectrometry can improve the care of our patients.

8:30 PMYour

Decision

ENJOY THE CITY@ Salzburg Old City

Explore the Old Town of Salzburg.

THURSDAY CLOSED

FRIDAY

8:00 AM9:00 AM

PLACE POSTERS@ Exhibit Hall / 1st Floor

Poster presenters for Friday must have their posters placed by 9 AM.

8:00 AM9:00 AM

WELCOME COFFEE@ Registration Foyer

Enjoy coffee, a muffin and a chat with colleagues before the day starts.

PLENARY LECTURE SERIES@ Mozart HallChair: TBA

9:00 AM9:45 AM

Steroid Metabolomics as a Discovery ToolWiebke ArltInstitute of Metabolism & Systems Research, University of Birmingham, UKOur group employs steroid metabolomics to reveal the pathogenesis and identify diagnostic andprognostic biomarkers in steroid­producing and steroid­dependent disease. Our approach uses gaschromatography ­ mass spectrometry (GC­MS) and liquid chromatography­tandem massspectrometry (LC­MS/MS) coupled with computational data analysis by machine learning­basedapproaches. I will present a number of examples including adrenal disorders, hypertension andsteroid­dependent cancer to illustrate the power of this approach.

9:45 AM10:30 AM

Innovative Instrumentation and Methods for the Identification of Intact Proteins inMixtures and for Sequence Analysis of Antibodies and Posttranslationally­Modified, IntactProteins on a Chromatographic Time­ScaleDonald HuntUniversity of VirginiaThis lecture will focus on data generated with a new ion source that facilitates simultaneousgeneration of positively charged sample ions by electrospray ionization and negatively chargedreagent ions for both electron transfer dissociation (ETD) and ion­ion proton transfer (IIPT)reactions on Orbitrap mass spectrometers. Implementation of multiple C­trap fills for enhancedsensitivity will be discussed and both parallel peak parking, and ion ejection strategies to facilitateprotein separation and enhanced sequence coverage of intact proteins will be described. Use ofIIPT/ETD facilitates near complete sequence coverage on many intact proteins and is ideallysuited for locating multiple posttranslational modifications on the same protein molecule.Sequence analysis of antibodies with an enzyme reactor that generates 3­10 KDa fragments inseconds will also be discussed. If time permits, the lecture will also provide an update on the useClass I MHC phosphopeptides for the immunotherapy of cancer.

10:30 AM

COFFEE BREAK@ Exhibit Hall / 1st Floor

Visit the Exhibit Hall to procure coffee, juice, water and/or snacks. Explore what's on offer from the Exhibiting vendors,reconnect with colleagues, or go for a short walk outside to refresh for the next session. POSTER PRESENTERS: If youare presenting a poster today your poster should have been up 2 hours ago. If it is not up please put it up immediately.

06/09/2015 MSACL 2015 EU Program

https://www.msacl.org/2015_EU_program/ 13/20

11:15 AMSponsored by:

GENERAL SCIENTIFIC SESSION 3

Track 1Mozart 1­3Sample Prep

Chair: ChristophSeger

Track 2Mozart 4­5

Renal MetabolomicsChair: Rochat Bertand

Track 3Papageno Hall

Cancer BiomarkersChair: Bruno Domon

Track 4Paracelsus Hall

ImagingChair: TheodoreAlexandrov

Track 5Trakl Hall

Case Historiesin BasicMethod

DevelopmentChair: JudyStone

11:15 AM11:40 AM

FerromagneticParticles as a Rapidand Robust SamplePreparation forAbsoluteQuantification ofEicosanoidsAnna Catharina Suhr

LaboratoryMedicine, Munich(LMU)Long Abstract | BioWe usedferromagneticparticles as a noveltechnique todeproteinize plasmasamples prior toUHPLC­MS/MSanalysis for thequantification ofimportant lipidmediators. Acombination of"ferromagneticparticle enhanceddeproteination" andsubsequent "on­linesolid phaseextraction" realisesquick and convenientsample preparation aswell as it provideshigh sensitivity androbustness. We wereable to show that thisapproach allowsaccurate and precisequantification ofseven exemplaryeicosanoids (TXB2,PGE2, PGD2, 5­HETE, 11­HETE,12­HETE, andarachidonic acid).The use of this semi­automated samplepreparation facilitatesthe screening of large

Development ofQuantitative UPLC­MS/MS Method forClinical Diagnostic ofRare Kidney Stones andKidney FailureFinnur Eiriksson

University of IcelandLong Abstract | BioAdeninephosphoribosyltransferase(APRT) deficiency resultsin excessive urinaryexcretion of poorlysoluble 2,8­dihydroxyadenine (DHA)causing kidney disease.Treatment withallopurinol and febuxostatprevents the disease inpatients with APRTdeficiency. Therapeuticdrug monitoring iscurrently performed byurine microscopy but amore sensitive andreliable method is needed.A UPLC­MS/MS methodwas developed andutilized to measure theconcentration of DHA inurine samples from 28patients, before and aftertreatment with allopurinolor febuxostat. Significantchanges were observed inurinary excretion of DHAafter pharmacotherapywas initiated. A decreasein the DHA­to­creatinineratio was observed withboth allopurinol andfebuxostat therapy. Thedeveloped UPLC­MS/MSassay will greatlyfacilitate clinicaldiagnosis and therapeuticdrug monitoring inpatients with APRT

Determination ofEGFR and VEGFSignaling PathwayActivity byImmuno­MALDITargeting Akt1 andAkt2 in ColorectalCancer TumoursRobert Popp

UVic ­ Genome BCProteomics CentreLong Abstract | BioTargeted treatment ofcolorectal cancer(CRC) only works ina minority ofpatients, and reliablemethods to quantifysignaling pathwayactivity are lacking.We therefore set outto develop immuno­MALDI (iMALDI)assays to determineexpression levels andstoichiometry ofcriticalphosphorylation sitesin Akt1 (P31749) andAkt2 (P31751) incancer cells andtumours. Wequantified non­phosphorylated Akt1from 100 µg proteinof breast and CRCcells (MDA­231,SW480 andHCT116), and breastcancer tumours. Non­phosphorylated Akt2has been quantifiedin 100 µg MDA­231breast cancer cells.Recently, weimproved sensitivityby 10­fold, whichallowed decreasingthe sample amount

MolecularAnnotation andMapping of BigData from SpatialMetabolomicsTheodoreAlexandrovEuropean MolecularBiology LaboratoryLong Abstract | Bio |Financial DisclosureSpatial metabolomicsis emerging as apowerful approach tolocalize hundreds ofmetabolites directlyfrom sections ofbiological sampleswith the grandchallenge to be in themolecular annotationof big data generated.Existingbioinformatics toolscannot be applieddirectly because ofthe sheer data sizeand high complexityof spectra. Wedeveloped algorithmsfor molecularannotation for HighResolution ImagingMass Spectrometrythat integrates bothspectral and spatialfilters and map theresults ontometabolic pathways.We will present ourefficientimplementation usingmodern big datatechnologies andapply it to 3D cellspheroids, microbialagar plates, andbiological tissues.We will present theEuropean project

Brief LC TopicReview ­ TheBasics ofModifyingMobile Phaseand StationaryPhaseChemistries toAchieveResolutionJudy StoneUniversity ofCalifornia, SanDiego HealthSystemWith modernliquidchromatography­tandem massspectrometry(LC­MSMS)– itis sometimessaid that tandemMS aloneconveyssufficientselectivity andtherefore LCseparation is notalwaysnecessary.However LC hastremendouscapability toimprove MSMSquantitation byreducing positiveinterferencefrom isobariccompounds andnegativeinterferencefrom ionsuppression.When you needthat additionalspecificity it isuseful tounderstand howand when

06/09/2015 MSACL 2015 EU Program

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study cohorts. Ingeneralferromagneticparticles mightsmooth the trail toautomation inUHPLC­MS/MS.

deficiency. from 100 µg to 10µg. The current lowerlimit of detection is0.35 pg Akt1/µglysate protein. Wehave developediMALDI Akt1 andAkt2 assays forquantitation of non­phosphorylated Akt1and Akt2.

METASPACE onBioinformatics forSpatialMetabolomics.

stationary andmobile phasechemistriesversus gradient,flow rate,column andparticledimensions canbe manipulatedto improveresolution. Wewill review thepracticalities ofoptimizing themobile phaseorganiccomponent andmodifiers andinterrogatingdifferentstationaryphases.

11:40 AM12:05 PM

Solid NanostructureMatrices for SmallMolecule Detectionby MALDI­TOFMS for ClinicalApplicationsJo­Il KimYonsei UniversityLong Abstract | BioTwo kinds of solidnanostructurematrices, TiO2nanowires andfunctional nanowebs,were synthesized todetect smallmolecules fromhuman serum anddairy milk samplesby MALDI­TOF MS.TiO2 nanowires weresynthesized by top­down hydrothermalprocess, andfunctional nanowebswere synthesized byelectrospinning onthe metal plate. Thefeasibility ofapplying solidnanostructurematrices to MALDI­TOF MS wasdemonstrated by thedetection of shortpeptides and aminoacids. For the realsample analysis,amino acids andantibiotics werespiked into humansera and milk,respectively. The

Urinary MetabolicProfiling as Method toAssess KidneyFunctionalityTiziana Pacchiarotta

LUMC (Leiden UniversityMdical Centre)Long Abstract | BioIschemia/reperfusioninjury (IRI) is aninevitable event afterkidney transplantation,leading to extensiveinjury and poor graftsurvival. Current markersfor the evaluation of IRIare considered insensitiveand reliable markers arehighly needed. Here weuse a well­established ratmodel to document theprotective role of MBL inrenal IRI as target fortherapeutic interventionin kidney transplantationand we show that theurinary metabolic patterncan be used to evaluate anin­tissue IRI event. Usinga combination ofstatistical models, we linkthe metabolic trajectoryto the recovery processunder different antibodytreatment. Wedemonstrate that“protective” urinarymetabolic signaturecorrelates with expressionof GRP 78.

The C­terminalFragment ofProstate­specificAntigen, a 2331 DaPeptide, as a NewUrinaryPathognomonicBiomarkerCandidate forDiagnosing ProstateCancerKenji NakayamaShimadzu Techno­Research (KyotoUniv. Hospital)Long Abstract | Bio |Financial DisclosureProstate cancer (PCa)is one of the mostcommon cancers andleading cause ofcancer­related deathsin men. Massscreening has beencarried out since the1990s using prostate­specific antigen(PSA) levels in theserum as a PCabiomarker. However,PSA is not a cancer­specific marker.Therefore, our aimwas to discover newbiomarkers for thediagnosis of PCa. Wefocused on urinesamples voidedfollowing prostatemassage andconducted apeptidomic analysisof them using

Mass SpectrometryBased MolecularImaging forProbing Aβ­PlaquePathology inTransgenicAlzheimer’s DiseaseMice Jörg Hanrieder

University ofGothenburgLong AbstractThe majorpathologicalhallmarks ofAlzheimer’s disease(AD) is theprogressiveaccumulation andaggregation of beta­amyloid (Aβ) andphospho­tau, intoneurotoxic deposits.However, the exactmolecular processesunderlying proteinaggregation andplaque pathologyremains unknown.The primary goal ofthis project was toemploy advancedmolecular imagingmass spectrometry(IMS) to probe thechemical andstructural aspects ofAβ plaque pathologyin experimental AD.MALDI IMSfollowed bymultivariate image

SerumAldosterone ­An LC MethodDevelopmentCase Study fora DifficultAnalyte (Part 1)Grace van derGugtenProvidenceHealthFor the mostpart, LC­MS/MSassaydevelopment andvalidation is, andshould be, awithin­laboratoryproject.However, thenew user canfind assaydevelopment adaunting task.We will describethe LC methoddevelopment forone of our morechallenging tomeasureendogenoussteroids:serum/plasmaaldosterone. Wewill discussselection ofmobile phases,columnselection,gradient programdevelopment,interference

06/09/2015 MSACL 2015 EU Program

https://www.msacl.org/2015_EU_program/ 15/20

spiked analytes inserum and milk weredetected qualitativelyand quantitativelyusing solidnanostructurematrices.

MALDI­TOF/MS.Multivariate analysisof the mass spectra ofurinary extractsrevealed a 2331 Dapeptide as a C­terminal PSAfragment. Theirquantitative analysesusing MALDI­TOF/MS revealedthat the peptide maybe a newpathognomonicbiomarker candidatethat can differentiatePCa patients fromnon­cancer subjects.Those results indicatethat the peptide maybecome a newpathognomonicbiomarker for thePCa diagnosis.

analysis reveal regionspecific accumulationof differentlytruncated amyloidpeptides in variousregions of the brain.Moreover, differentprotein species wereselectively regulatedin plaque proximity.In conclusion, MSimaging is apromising approachto probe plaquechemistry inAlzheimer's disease.

testing, andaddition ofcortisol to themethod.Importantly, wewill coverunexpectedworkflowchallenges andcontinualimprovementsand discoverieswe have madewhile the assayhas been inclinicalproduction.

12:05 PM12:30 PM

Development of aUPLC­MS/MSMethod to MeasureNeurotransmittersand Trace Aminesin Human PlasmaAntonina Gucciardi

University of Padova,ItalyLong Abstract | BioWe developed andvalidated a methodfor measurement ofplasmaneurotransmitters(dopamine,epinephrine,norepinephrine,serotonin) and traceamines (tyramine,octopamine,synephrine, β­phenylethylamineand tryptamine) byUPLC­MS/MS.Analytes wereextracted using weakcation exchange SPEand separated by aPFP column andwater­acetonitrile­methanol gradient asmobile phase, intothe ACQUITYUPLC system. Themetabolites weremeasured in MRMmode with positiveelectrosprayionization using a

Nanoelectrospray HighResolution MassSpectrometry or LiquidChromatography HighResolution MassSpectrometry forUrinary MetabolicProfiling? Elena Chekmeneva

Imperial College LondonLong Abstract | BioWe present a practicalcomparison of nESI­HRMS and reversed­phase UPLC­MS methodsfor multiplexed targetedand global metabolicprofiling of the urinespecimens from theINTERMAP study. Thetest set consisted of 132randomly selectedsamples which included22 pairs of blindedreplicated and differenttypes of quality controlsamples. Selectedmetabolites werequantified using thestable isotope labelledinternal standards (IS).Both methods werevalidated according to theFDA guidelines. Thequantification results,sensitivity and dynamicranges were assessed andcompared between twomethods. Theclassification ability was

CESI­MS as a Toolfor GlycosylationAnalysis of PSA andImprovedIonizationEfficiency withAcetonitrile­enriched NebulizerGasGuinevere S. M.Kammeijer

Leiden UniversityMedical CenterLong Abstract | Bio |Financial DisclosureA powerful analyticalplatform for theanalysis ofbiomolecules iscapillaryelectrophoresis –electrosprayionization – massspectrometry (CESI­MS). Implementationof an acetonitrile­enriched nebulizergas on the CESI­MSsystem yielded amore robust platformas well as a gain insensitivity comparedto the conventionalplatform. The gain insensitivity could aidin the analysis ofsamples which areonly available inminute amounts. Theconventional CESI­

Diagnostic andPrognosticBiomarkerDiscovery of SoftTissue Sarcomas byMass SpectrometryImagingSha Lou

Leiden UniversityMedical CenterLong Abstract | BioAbility of Matrix­assisted laserdesorption/ionizationMass SpectrometryImaging todistinguish betweenthe most encounteredbut clinicallychallenging highgrade Soft TissueSarcomas (foursubtypes) wereinvestigated (leadingto diagnosticbiomarkersdiscovery) and ifthere are individualproteins (signatures)that are statisticallyassociated withpatient survival anddevelopment ofmetastases were alsoinvestigated (thuswould be prognosticbiomarkers). Twentyprotein peaks werefound as diagnosticbiomarkers. Fourteen

SerumAldosterone ­An LC MethodDevelopmentCase Study fora DifficultAnalyte (Part 2)Grace van derGugtenProvidenceHealthFor the mostpart, LC­MS/MSassaydevelopment andvalidation is, andshould be, awithin­laboratoryproject.However, thenew user canfind assaydevelopment adaunting task.We will describethe LC methoddevelopment forone of our morechallenging tomeasureendogenoussteroids:serum/plasmaaldosterone. Wewill discussselection ofmobile phases,columnselection,gradient program

06/09/2015 MSACL 2015 EU Program

https://www.msacl.org/2015_EU_program/ 16/20

Waters Xevo TQ­Smass spectrometer.Commercially qualitycontrol (QC)materials fromChromsystems wereused for validation.The method showedgood precision,specificity,sensitivity andlinearity, and will beuseful for clinicalresearch ofneurodegenerativedisease.

examined on the basis ofthe multivariate analysisof the global profiles.

MS method was usedfor the analysis of theglycoprotein prostatespecific antigen(PSA). We were ableto identify 50different N­glycanson a single N­glycosylation site(N69). The usedmethod shows greatpotential for studyingPSA in prostatecancer research toidentify diseaserelated alterations ofglycosylation in anearly stage andtherefore could be apromising tool fordiagnostic andprognosticevaluation.

protein peaks werefound as prognosticbiomarkers. Based oncomparisons withdatabases, Acyl­CoA­binding protein,Macrophagemigration inhibitoryfactor, Thioredoxinand Galectin­1 weretentatively assignedamong diagnosticbiomarkers;Thymosin beta­10,Proteasome activatorcomplex subunit 1,two modified HistoneH4 were tentativelyassigned amongprognosticbiomarkers.

development,interferencetesting, andaddition ofcortisol to themethod.Importantly, wewill coverunexpectedworkflowchallenges andcontinualimprovementsand discoverieswe have madewhile the assayhas been inclinicalproduction.

12:30 PM2:30 PM

LUNCH@ Exhibit Hall / 1st Floor

Lunch to be provided in the Exhibit Hall. • Get ready to join a Corporate Workshop.

Sponsored by:

1:30 PM2:30 PM

POSTERS@ Exhibit Hall / 1st Floor

All Posters to be attended from 1:30 ­ 2:30 PM.

2:30 PM3:30 PM

CORPORATE WORKSHOPS (2:30 ­ 3:30 PM)

WatersMozart 1­3

UPLC­MS/MS­BasedStudies of Vitamin DMetabolism: LessonsLearned from CYP24A1Knockout Mice and MenMartin Kaufmann, Queen’sUniversity, KingstonCanadaPre­Register

Vitamin D function in thebody is partly regulated bycatabolism of 1,25­(OH)2Dand 25­OH­D by CYP24A1.We have developed asensitive assay usingACQUITY/TQ­Sinstruments to quantitatemetabolites formed byCYP24A1 including 24,25­(OH)2D3, in addition to 25­OH­D. The talk will focuson the application of our

SCIEXMozart 4­5

Mass SpectrometryApplications for ClinicalResearchDr Robert Graham and DrMichael WrightPre­Register

In this workshop we bringtogether scientists, cliniciansand biochemists that hold aninterest in the use of MassSpectrometry in the areas ofClinical Research as wediscuss what can achievedwith today’s technology andwhat we can expect in thefuture. We have twospeakers delivering thisworkshop. Dr RobertGraham is Senior Lecturerin Clinical Proteomics at theUniversity of Manchester,UK. Dr Graham will discuss

PhenomenexPapageno Hall

Workshops on NavigatingSample Prep Techniques& Leveraging the Power ofMicrosampling1. Navigating SamplePreparation Techniques inthe Clinical LCMSLaboratorySean Orlowicz Manager­PhenoLogixHave you ever askedyourself, "Which SamplePrep Technique is right forthis analysis?" If so, you arenot alone. In this talk wewill investigate, throughcase studies, somedifferences betweencommon sample preparationtechniques.

2. Leverage the Power ofMicrosampling to Benefit

TecanParacelsus Hall

Workshops on MethodAutomation1. Automation andValidation of a SPEMethod for the Analysis of23 Opioids, Cocaine, andMetabolites in Urine withUHPLC­MS/MSMaria del Mar RamirezFernandez, NationalInstitute of Criminology andCriminalistics, Belgium

2. Automated LC­MS/MSmethods for ClinicalDiagnostics ­ Realized forTherapeutic DrugMonitoring and Vitamins Dr. Silvia Bächer, R&D,RECIPE Chemicals +Instruments GmbH

3. Automated SPE MethodDevelopment using

06/09/2015 MSACL 2015 EU Program

https://www.msacl.org/2015_EU_program/ 17/20

assay to a uniquecombination of samplesfrom CYP24A1­null miceand patients withinactivating mutations toCYP24A1 (IdiopathicInfantile Hypercalcemia) aswell as subjects takingvitamin D supplements. Wereveal that the ratio of 25­OH­D3:24,25­(OH)2D3 is auseful tool to predict thepresence of CYP24A1mutations as well vitamin Ddeficiency.

the use of advanced accuratemass MS technologies inovarian cancer biomarkerresearch We also have DrMichael Wright, from thePrince of Wales Hospital,Sydney, Australia Dr Wrightis Senior Leader of clinicalChemistry andEndocrinology. In theworkshop he will discussnovel and advanced MStechnologies specificallywith respect to their use inreducing background andmatrix effects in sampleanalysis.

Both Your Patient andYour LaboratoryJames Rudge Ph.D. ­SeniorBusiness DevelopmentManager – Europe Hospital, clinical, andwellness/biomarkerscreening labs are usingMitra Microsampling toprovide a better, moreconvenient experience totheir patients, while at thesame time reducing costsand streamlining workflows.In this workshop, we willdiscuss the details of an at­home sampling workflow,from collection throughanalysis, including theoptimization and automationof extractions for clinicalsamples

StrataTM – X 96­WellSPE Method DevelopmentPlates in Conjunction witha Tecan Freedom EVO®Liquid Handling PlatformSean Orlowicz, Manager­Phenomenex

Customer experience andcommercial insights will bepresented for applyingautomated MS samplepreparation in areas ofclinical and forensic sampletesting, such as therapeuticdrug monitoring, DOA­ andVitamin testing. We havepulled together speakers thatwill present most relevantautomated methods andprovide guidance onsuccessfully implementinglab established and kit basedmethodologies.

3:30 PM4:00 PM

COFFEE BREAK@ Registration Foyer & Front Patio

Visit the Registration Foyer to procure coffee, juice, water and/or snacks. Reconnect with colleagues, or go for a short walkoutside to refresh for the next session.

Sponsored by:

GENERAL SCIENTIFIC SESSION 4

Track 1Mozart 1­3Endocrine

Chair: Brian Keevil

Track 2Mozart 4­5Advances inMetabolomicsChair: OlegMayboroda

Track 3Papageno HallProteomics

Chair: Donald Hunt

Track 4Paracelsus HallMetabolomicsChair: Dietrich

Matern

Track 5Trakl Hall

Intro to SamplePrep II

Chair: Grace van derGugten

4:00 PM4:25 PM

The Importance ofAccurate andSensitive OestradiolMeasurement &Strategies toAchieve thisDifficult TaskLaura OwenUniveristy Hospitalof South ManchesterLong Abstract | BioOestradiolmeasurement istraditionallyperformed byimmunoassays whichhave poorperformance at lowerconcentrations. It isimportant toaccurately measureoestradiol at low

MetabolicPhenotypingReveals a LipidMediator Responseto IonizingRadiationGiuseppe AstaritaGeorgetownUniversityLong Abstract |Financial DisclosureExposure to ionizingradiation hasdramaticallyincreased in modernsociety, raisingserious healthconcerns. Themolecular response toionizing radiation,however, is still notcompletely

Novel Insights intoApolipoproteinMetabolism in Miceand Man byApplication of aTargeted Peptide­based LC­MS/MSAssayUta CeglarekUniversity HospitalLeipzigLong Abstract | Bio |Financial DisclosureApoproteins are keycomponents oflipoproteins andmediate diversefunctions in lipidtransport andmetabolism. A LC­MS/MS methods toanalyze apoproteins

Why High­resolution­MS IsBecoming the NewGold Standard MSAnalyzer in ClinicalLabsBertrand RochatCHUV ­ qMSFLong Abstract | BioAs we see more andmore demonstrationsof the capability ofhigh­resolution (HR)­MS instruments toperform sensitive andreliable quantificationof a large variety ofanalytes in HR­fullscan mode, we canconsider that HRMSis the new goldstandard MS analyzer

Brief SamplePreparation TopicReview ­ ExtractionOptions for Neutral,Non­Polar Analytesin Serum ­ SayGood­By toPhospholipidsJudy StoneUniversity ofCalifornia, SanDiego Health SystemExtraction protocolsthat concentrateneutral, non­polarserum analytes topg/mL lower limits ofquantitation andremove enoughmatrix to produce arobust method arechallenging to

06/09/2015 MSACL 2015 EU Program

https://www.msacl.org/2015_EU_program/ 18/20

concentrations incertain patient groupse.g. females withbreast cancer. Massspectrometry is anattractive alternativedue to its betterspecificity andperformance at thelow concentrations.We have investigateddifferent mechanismsfor improving thesensitivity of ourcurrent oestradiolassay. Furtherinvestigation into theinterference of breastcancer medicationshas shown that one inparticular, fulvestrantcauses directinterference in twoimmunoassays. Theother medications(anastrozole,exemestane andtamoxifen) do notappear to directlyinterfere.

understood. Here wescreened mouseserum for metabolicalterations followingan acute exposure togamma radiationusing a multi­platform, mass­spectrometry­basedstrategy. A global,molecular profilingrevealed that mouseserum undergoes aseries of significantmolecular alterationsfollowing radiationexposure. Weidentified andquantified bioactivemetabolitesbelonging to keybiochemicalpathways andeicosanoids, whichcould be utilized asan indicator ofradiation exposureand as novel targetfor therapeuticintervention.Monitoring such amolecular response toradiation exposuremight haveimplications not onlyfor radiationpathology but also forcountermeasures andpersonalizedmedicine.

using species­uniquepeptide sequences forApo A­I, Apo A­II,Apo A­IV, Apo B48,Apo B100, Apo C­I,Apo E and Apo J in 3µl human or murineplasma. In humanplasma Apo A­I andApo A­II showed thehighestconcentrations. Thesimultaneous analysisof apoproteins in only3 µl murine andhuman plasma allowsus a comprehensivecharacterization ofapolipoprotein levelsusing normo­ andhyperlipidemicpatients and differentmice strains underdifferent nutritionalconditions.

for LCMS analyses(quantitative andqualitative). Examplesshowing the versatilityand the performancesof HRMS in HR­fullscan will bepresented: 1) routinequantification of drugsand endogenousmetabolites in plasmaextracts, 2) Qual/Quananalysis in a study ofthe fate of tamoxifendrug in humans and 3)targeted anduntargetedmetabolomics.

develop. Serumphospholipids arepresent at mg/mLconcentrations andcontain a chargedphosphate group andnon­polar fatty acids.This amphipathicstructure complicatesremoval ofphospholipids duringextraction.Insufficient removalof phospholipids maycause substantial LC­MSMS ionsuppression andcompromised methodrobustness ­­shortened columnlifetimes, shiftingretention times, highbaselines, anddecreased MSMSsensitivity. We willreview commonlyused LC­MSMSextraction protocolsfor the ability toconcentrate non­ionizable analyteswhile optimallyremoving serumphospholipids.

4:25 PM4:50 PM

Eve’s Curse: HowBest to MeasureEstradiol Across aBroad Spectrum ofReproductiveEndocrineDisorders inWomenMichael WrightPrince of WalesHospitalLong Abstract | BioEstradiol is arguablythe most potent sexsteroid in humanbiology requiringrelatively smallconcentrations toexert largephysiological effectsin comparison to itsprecursor,testosterone.However, thedelivery of a clinical

TargetingResistance toProteasomeInhibitor Therapy:A MetabolomicsApproachCelia Berkers

Utrecht UniversityLong Abstract | BioProteasome inhibitionhas emerged as animportant strategy forthe treatment ofcancer. However,treatment withproteasome inhibitorsis often hampered bythe occurrence ofboth primary andacquired resistance.We embarked onunravelling themetabolic mode ofresistance to the

Top­down MassSpectrometryMethods forHemoglobinDisorders DiagnosisDidia Coelho Graça

University of GenevaLong Abstract | BioLow and high­resolution top­downmass spectrometry(MS) methods weredeveloped forhemoglobin disorderscharacterization. Anautomated workflowusing an ion­trap withETD capabilitiesallowed to identifythe most clinicallysignificanthemoglobin variantsand to quantifyhemoglobin chains.

Identification andCharacterisation ofOxygenatedPorphobilinogenDerivatives and theirAmino Acid/peptideConjugates UsingLiquidChromatography­accurate Mass Christopher BentonAgilent TechnologiesLong Abstract |Financial DisclosureStudying themodification ofporphobilinogen isimportant when tryingto understand thepathogenesis of theperipheral neuropathy,chronic renal failureand hepatocellularcarcinoma observed inthe AHP. Using

A SamplePreparation MethodDevelopment CaseStudy ­ Trials andTribulations withSerum Testosterone(Part 1)Grace van der GugtenProvidence HealthUse of liquidchromatography­mass spectrometryfor analysis of smallmolecules in clinicallaboratories hasincreased in the pastfew years. Animportant componentof developing a massspectrometry methodis the samplepreparation techniqueemployed in order tosufficiently clean upthe sample without

06/09/2015 MSACL 2015 EU Program

https://www.msacl.org/2015_EU_program/ 19/20

diagnostic estradiolservice is asignificant challengefacing manylaboratories. In thisstudy we look at anumber of sampleextraction options,chromatographictechniques andmultistagefragmentation(MRM3) usingquadrupole linear iontrap instruments tocreate robust LC­MSmethods that meet therequirements of lowlevel measurement.In this presentationwe propose threedifferent methods tomeet the needs of ourdiverse patientpopulation.

proteasome inhibitorbortezomib. To thisend, we profiledbortezomib­sensitiveand ­resistant celllines, combiningsteady­statemetabolomics screenswith metabolic fluxstudies using stableisotope labellingapproaches. Ourstudies revealed thatthe metabolic profilesof bortezomib­sensitive and resistantcells differedsignificantly. Inparticular, resistantcells were moredependent on theuptake of specificnutrients from theirenvironment.Together, our dataindicate a potentialrole for nutrientstarvation in thetreatment ofbortezomib­resistanttumours.

Analyticalperformancesachieved with thismethod werecompared to goldstandard assays usedin clinical labs. Ahigh­resolutionmethod was alsodeveloped forhemoglobin variantsidentification.Selected diagnosticproduct ions wereused for fast andreliable datainterpretation by non­expert users. MSbrings more preciseinformation at theprotein level thanprotein analysismethods currentlyused for hemoglobindisorders diagnosis.

LC/HRMS wedemonstrate how PBGcan form variousoxygenated species,derived from reactiveepoxide,hydroperoxide andendoperoxideintermediates.Furthermore, theseintermediates formedadducts with aminoacids and peptides,highlighting theirreactivity. Themechanisms offormation of theseconjugates arepostulated to be viaepoxyporphobilinogenand PBGendoperoxideintermediates. Ifformed in vivo, suchcompounds couldcovalently bind tocellularmacromolecules, suchas proteins andnucleic acids, alteringtheir biologicalfunction.

sacrificing analyterecovery. A numberof references outthere detail samplepreparationtechniques but whichone do you choose?This presentation willdetail the thoughtprocess behind thesample preparationtechnique choice formeasurement ofserum totaltestosterone in onelaboratory, includingthe balancing act ofwhat you want to,and what you canrealistically achieve. (Courtesy of DeborahFrench)

4:50 PM5:15 PM

Clinical Utility ofReporting 3­Methoxytyramine asPart of a PlasmaMetanephrinesProfileSarah Pitkin

UCL Hospitals NHSFoundation TrustLong Abstract | BioThe utility ofreporting thedopamine metabolite3­methoxytyramine(3­MT) in plasmafree metanephrinesprofiles has beenquestioned due toanalytical and clinicalconcerns. Wedeveloped andvalidated an LC­MS/MS assay forplasma freemetanephrines,including 3­MT, andreviewed theanalytical and clinicalutility of reporting 3­MT over a 1 yearperiod. Performanceof the assay in an

Combining DriedBlood Spots withStable­isotopeTracers to ProfileDynamics ofGlucose Metabolismin Human SubjectsKarsten HillerUniversity ofLuxembourg, LCSBLong Abstract | Bio

Karsten Hiller isunable to attend asof Sept 3. This talkwill be presentedby Jean­PierreTrezzi.Here, we presenttime­resolveddynamics of glucosemetabolism in bloodafter oraladministration of 13Cstable­isotope labeledglucose in humansubjects. To extractabsolute flux valuesfor glucoseproduction (GP),glucosedisappearance (GD)and gluconeogenesis

Linkage­specificSialic AcidDerivatization forMALDI­TOF­MSProfiling ofGlycoconjugatesNoortje de Haan

Leiden UniversityMedical CenterLong Abstract | BioGlycosylation isamong the mostcommon co­ andpost­translationalproteinmodifications,affecting thephysiological andbiochemicalproperties of aprotein in variousways. High­throughput proteinglycosylationanalysis may beperformed byMALDI­TOF­MS ofeither releasedglycans orglycopeptides. Thisapproach, however,biases the analysis of

Enzyme Assays forthe Diagnosis ofInborn Errors ofGalactoseMetabolism UsingLiquidChromatographyTandem MassSpectrometryDietrich MaternBiochemical GeneticsLaboratory, MayoClinicLong Abstract | BioGalactosemias areautosomal recessivedisorders that resultsfrom a deficiency ofone of three enzymescatalyzing theconversion ofgalactose to glucose:galactose­1­phosphateuridyltransferase(GALT),galactokinase(GALK), and uridinediphosphategalactose­4­epimerase(GALE). Weimplemented LC­MS/MS assays foreach enzyme that can

A SamplePreparation MethodDevelopment CaseStudy ­ Trials andTribulations withSerum Testosterone(Part 2)Grace van der GugtenProvidence HealthUse of liquidchromatography­mass spectrometryfor analysis of smallmolecules in clinicallaboratories hasincreased in the pastfew years. Animportant componentof developing a massspectrometry methodis the samplepreparation techniqueemployed in order tosufficiently clean upthe sample withoutsacrificing analyterecovery. A numberof references outthere detail samplepreparationtechniques but whichone do you choose?This presentation will

06/09/2015 MSACL 2015 EU Program

https://www.msacl.org/2015_EU_program/ 20/20

external qualityassurance schemewas excellent.Clinically, 3­MT wasfound to be avaluable addition tothe profile, providinga useful tumourmarker for long termmonitoring in onepatient. Cabergolinetherapy was found todecrease plasma 3­MT, whereaslevodopa raised it.

(GNG)on a wholeorganism scale indiabetes patients, wedeveloped a simplemathematical ODEbased dynamic modelthat considers themain fluxes of (13Clabeled) glucose intoand out of the blood.In combination withthe time­resolvedenrichment patterns(Mass IsotopomerDistributions /MIDS) and absoluteconcentrations of thetarget metabolitesobtained from DBSsampling and GC/MSmeasurement, wecould determinequantitative androbust values for GPand GNG for eachstudied subject.

sialylatedglycoconjugates bymetastable decay andvariations inionization. Here, wepresent approachesfor the linkage­specific sialic acidderivatization of bothreleased glycans andglycopeptidesfollowed by MALDI­TOF­MS analysis.The methods are fastand have an excellentintra­ and inter­dayrepeatability. Weenvision the use ofthese methods for themonitoring of proteinglycosylation, both inthe analysis ofbiopharmaceuticalsand for the detectionof glycomic diseasebiomarkers.

be performed from thesame specimen. 843controls and samplesfrom known patients(GALT: n=161;GALK: n=1; GALE:n=6) andasymptomaticmutation carriers(GALT: n=92) wereanalyzed to determinereference ranges.These tests provide acomprehensive andcost­effectivelaboratory evaluationto quickly resolveabnormal NBS resultsfor galactosemia or adiagnosis of other at­risk patients.

detail the thoughtprocess behind thesample preparationtechnique choice formeasurement ofserum totaltestosterone in onelaboratory, includingthe balancing act ofwhat you want to,and what you canrealistically achieve. (Courtesy of DeborahFrench)

5:15 PM7:15 PM

CLOSING RECEPTION@ Registration Foyer & Front Patio

Enjoy some last bits of time mingling with colleagues. Located in Registration Foyer and Front Patio, weather permitting.Appetizers and drinks to be provided.

Sponsored by:

FRIDAY CLOSED.