Mass Spectrometry Harmonisation

Mass Spectrometry HarmonisationDr Ronda Greaves

AACB MS Satellite Meeting 20/09/2013

RMIT University©2013 AACB Mass Spec Satellite Meeting 1

Declaration of Interest / Disclosures

No conflict of interest exists in relation to this presentationrelation to this presentation

Many individuals and companies have supported aspects f h k d h h l d h h of the work presented here. They are listed throughout

the presentation and in the acknowledgements.


Overview• Clinical Relevance

Ch ll ith th i t t ti f–Challenges with the interpretation of paediatric hormone test results

A littl th• A little theory–Dull but worthy!

• Practice–APFCB MS Testosterone


harmonisation

1. CLINICAL

RMIT University©2013 AACB ASM Gold Coast Australia 4

A challenging population - Preterm Infants

Australasia• ~3000 infants < 1500 g are born in

Endocrine• Frequent endocrine testing including

Australia and New Zealand annually– Survival rates ≈ 85%

• Premature neonates, in particular

gonadotrophins & androgens

• Little normative data available for this cohort

extremely premature neonates, suffer from a number of common morbidities

– Developmental impairmentC b l l

• Males– More likely to be born preterm – Have increased risk of morbidity

– Cerebral palsy– Resistant hypotension – Prolonged ventilatory support

I t it f th d i t d it

– Increasing recognition of male vulnerability

• Females– Genital appearance is often unusual with

questions of possible ambiguity of female infants• Immaturity of the endocrine system and its potential impact on morbidity is the subject of numerous studies

questions of possible ambiguity of female infants raised by neonatal teams

RMIT University© AACB Mass Spec Satellite Meeting 5

Oldish data


Early Work 1: Neonatal Steroid chromatogramsFull term neonate

4 days of age

P t t


Preterm neonate6 weeks of age

Early Work 2• Aim to improve morbidity

1. To develop reference intervals for common hormonesmeasured in babies born <30 weeks’ gestation

2 T i ti t h t f t i f t t d t i

Cortisol

DHEAS2. To investigate a cohort of preterm infants to determinewhether hormone levels in the first six weeks of life wereassociated with volumetric or structural changes to thebrain at term corrected age

Only a small amount of blood can be

DHEAS

Free thyroxine (fT4)

G th H (GH)• Only a small amount of blood can be collected

• Iatrogenic anaemia

Growth Hormone (GH)

IGF-1 Iatrogenic anaemia

• Hormones prioritised based on:1. Literature

Oestradiol (E2)

Progesterone2. Perceived potential benefit for HRT3. Practical considerations of volume etc


Earlier work 2• 0.5 mL whole blood collected from cord

and then on days 1, 4, 7, 14, 21, 28 and 42, coinciding with routine blood sampling, g p g

• 130/198 eligible infants enrolled over 18 months

M F 65 65• M:F = 65:65

• Mean GA 26.9 weeks

• Mean birth weight 964 gg g

• 123 babies had hormone levels measured

• 113 survived until at least term corrected


• 100 MR brain scan at term corrected

Early Work 2: - 2 x E2 assays in preterm neonates


Early work 3: 4 x cases - all femaleyWhat about the gonadotropins?

Why did they measure these originally?

N li bl RINo reliable RI

Results not able to be interpretedp

Subset of cohort 1 samples analysed by immunoassay on the Centaur

Except for the USP, all assays performed by immunoassay

on the Centaur

Early study 3: normative data

• Samples collected from 39 female and 43 male infants born < 30 wks gestationgestation

• At time of collection age ranged from 0 – 42 days of age

• No ambiguous genitalia• No ambiguous genitalia

• No suspicion of other endocrine disorders

Greaves R , Hunt RW, Chiriano A, Zacharin M LH and FSH levels in Extreme Prematurity: Establishment of Reference Intervals Eur J Paediatr2008

Samples collected from 39 female & 43 male infants born < 30 wks gestation. No evidence for endocrine abnormality/ambiguity

At time of collection age ranged from 0 – 42 daysAt time of collection age ranged from 0 – 42 days

FEMALE GONADOTROPHIN LEVELS RELATIVE TO CORRECTED GESTATIONAL AGE

100.0

120.0

140.0

160.0

180.0

U/L FSH

Peak of LH 27 –29 weeks corrected age males (peak 13 IU/L),

0.0

20.0

40.0

60.0

80.0

25 27 29 31 33 35 37

RELATIVE GESTATIONAL AGE (WEEKS)

IU/

LH

MALE GONADOTROPHIN LEVELS RELATIVE TO CORRECTED GESTATIONAL AGE

14

16

28 –31 weeks in females (54 IU/L)

No peak of FSH far higher levels in females

Female

0

2

4

6

8

10

12

25 27 29 31 33 35 37

RELATIVE GESTATIONAL AGE (WEEKS)

IU/L FSH

LH Male

far higher levels in females

LH greater impact than FSH on potential development of ambiguity

Use of FSH:LH ratio importantLHFSH

Moving forwardPituitary hormones still need immunoassay

We know Mass Spectrometry will improved analysis of steroidsWe know Mass Spectrometry will improved analysis of steroids

LC-MSMS provides this tool


Current Work• Blood collected from 249 (129 male,120

female) extremely preterm infants

• Born between 24 and 35 weeks• Born between 24 and 35 weeks gestation

• at 2-3 week intervals, to 36 weeks gestational age

• No infant in this cohort had ambiguous genitalia or other endocrine abnormalitygenitalia or other endocrine abnormality

• Serum analysed by electrochemiluminescence immunoassay (Roche Cobas 8000immunoassay (Roche Cobas 8000 -E602 module) Abstract / Oral presentation 2013 ESPE meeting

What about the steroids?FSH LH ratio PRL Androstenedione (nmol/l) Testosterone (nmol/l) 17OH progesterone (nmol/l)31.17 3.27 0.1 1731 2.7 0.24 4.546.16 7.86 0.2 1059 2.7 0.4 11.157.7 26.65 0.5 1926 1.4 0.19 2.960.8 12.05 0.2 2163 1 0.13 3.763.94 27.48 0.4 1648 2.2 0.5 5.385.37 39.17 0.5 1149 2.1 0.3 13.5128 8 93 47 0 7 4732 3 0 3 12 1128.8 93.47 0.7 4732 3 0.3 12.1133.7 97.29 0.7 2282 3.6 0.5 6.8152.1 96.78 0.6 8187 1.1 0.16 6.1

9 200 168.6 0.8 3167 1.9 0.2 8.3n 10 10 10 10 10 10

median 74.7 33.3 2045 2.2 0.3 6.5mean 96.0 57.3 2804 2.2 0.3 7.4SD 54.8 54.2 2174 0.8 0.1 3.7SD 54.8 54.2 2174 0.8 0.1 3.7

upper limit = 200 LOQ = 0.3

FSH LH ratio PRL Androstenedione (nmol/l) Testosterone (nmol/l) 17OH progesterone (nmol/l)0.634 1.19 1.9 932.7 3.4 2.8 5.90.664 0.816 1.2 1008 2.5 0.3 17.20.931 7.06 7.6 1647 1.2 2.9 5.91.5 1.63 1.1 1261 1.4 1.1 5.71.54 6.64 4.3 1997 1.7 0.8 91.57 4.56 2.9 1725 2.4 2.3 10.71.66 1.61 1.0 1998 1.7 1.9 4.71.93 3.09 1.6 1859 1.9 2.6 71.99 4.2 2.1 3384 1 2.6 4.52.28 3.93 1.7 1252 0.9 3.5 5.5

n 10 10 10 10 10 10di 1 6 3 5 1686 1 7 2 5 5 9


median 1.6 3.5 1686 1.7 2.5 5.9mean 1.5 3.5 1706 1.8 2.1 7.6SD 0.6 2.2 707 0.8 1.0 3.9

Summary• Immunoassay results may or may not be comparable between platforms

• MS is the way forward for steroid and peptide analysis

• Measurands different - cannot compare immunoassay with mass spectrometry results

• Need reference intervals for current and also newer hormones

How do we know our MS results are “true”?

Does it matter?Does it matter?

RMIT University© SMS – Medical Sciences 17

2. THEORY


Westgard Essay – September 2013• “It took several years for the concept of total analytical error to be accepted in

medical laboratories. Some laboratory scientists argued that bias (or SE) was not that big an issue because laboratories’ reference ranges compensated fornot that big an issue because laboratories reference ranges compensated for existing biases. However, biases between methods became a more common

problem with the expansion of laboratory testing services and the implementation of different methods for the same measurand Today biasimplementation of different methods for the same measurand. Today, bias

remains a significant problem in healthcare and laboratory networks, particularly when electronic patient records intermix the test results without identifying the measurement procedures.” http://www.westgard.com/ate-tea.htm#estimationidentifying the measurement procedures. http://www.westgard.com/ate tea.htm#estimation

With mass spectrometry we have the opportunity now to get it right from the beginning


now to get it right from the beginningTo do this we need standardisation

Definitions:Standardisation =concept whereby agreement of test results is achieved by establishing traceability to higher order reference materials and measurement proceduresp

– This is achievable when the method base and the measurand can be clearly definedThe outcome of standardisation is agreement with established trueness– The outcome of standardisation is agreement with established trueness

Harmonisation = process of making agreement between methods in order to produce a consistent clinical interpretation irrespective of the laboratory p p p yin which samples are analysed

1. Harmonisation of calibration materialThe outcome of harmonisation does not necessarily equate to ‘trueness– The outcome of harmonisation does not necessarily equate to trueness

2. Harmonisation of the total testing processRMIT University©2013 AACB ASM Gold Coast Australia 20

CBR 2012;33:123 -

Pillars of Harmonisation1. Primary reference material

2. Primary reference method

3 Primary reference laboratory3. Primary reference laboratory

4. External Quality Assurance

5. Reference Intervals / Clinical Decision limitsDecision limits


• 1 Infrastructure• 1.Infrastructure

• 2. Definition of procedures

3 R l ti• 3. Regulation

• 4. Standardisation / harmonisation issues considered from the beginningconsidered from the beginning

• 5. Total Testing ProcessRMIT University©2013 AACB ASM Gold Coast Australia 22

Harmonisation as a three-level process• 1. Local: Adoption of international and national

recommendations; implementation of ‘ad interim’ laboratoryti f t it f i t l

Sweat Sweat TestingTesting

practices for measurement units, reference intervals,decision limits and SOP’s

• 2 National: Diffusion of internationally developed• 2. National: Diffusion of internationally developedguidelines; and release of laboratory practices forstandardisation and harmonization of all TTP steps,including communication of test results and critical values

Common Common RIRI

including communication of test results and critical values

• 3. International: Standardisation and among methodsharmonisation clinical practice guidelines for test

Vitamins Vitamins & & TestoTestoharmonisation, clinical practice guidelines for test

requesting and results interpretation


& & TestoTesto

STAGE 1Planningg

STAGE 2 Initial

A t

STAGE 6Ongoing R i AssessmentReview

HarmonisationC lEQA

STAGE 3Method &

STAGE 5

CycleEQACalibrator

STAGE 4RI CL units

Best Practice

RI, CL, units & reporting


Greaves R., CBR 2012; 33:123-132

Why is EQA central?• Independent umpire

• Level playing field

• Objective comparisonObjective comparison

• Ongoing review mechanism

• Encourages improvement


Encourages improvement

Definition: Traceability“Metrological traceability is defined by VIM as the ‘property of a

measurement result whereby the result can be related to a reference through a documented unbroken chain of calibrations, each g

contributing’ to the uncertainty of measurement.”“Such traceability requires an established hierarchy”

JCTLM database established 2002


CBR 2012;33:123 -

Joint Commission for Traceability in L b t M di i (JCTLM)Laboratory Medicine - (JCTLM)• EU Directive on Vitro Diagnostic

measurements requires traceability to standards of “higher order”

• JCTLM Established by BIPM, IFCC and ILAC

• In co-operation with all stakeholders

• Traceability to SI, but if not (yet) possible to other internationally agreed references (e.g. WHO units for biological activity)WHO units for biological activity)

• Aim of JCTLM is to realise and support worldwide reliable comparability and traceability of measurement results in laboratory medicine

RMIT University AACB Mass Spec Satellite Meeting 27

3. PRACTICEHARMONISATION WITH TRACEABILITY

– THE SERUM TESTOSTERONE PROCESS


Testosterone harmonisation:How – when – why?

2010 APCMS – meeting C f

Why Testosterone?• Conference:Asia Pacific Chromatography Mass

Spectrometry Meeting• Chairs:

• Initially steroids

• Simplified to one analyte

• Small number of labs• Chairs:Danny Sampson & CS Ho• Discussion:

Small number of labs

• Easier to control as the pilot

• No other group currently looking at Need for agreement b/w MS assays• Inaugural meeting:Saturday 16th January 2010

testosterone

• Difficult analyte to measure in children and females

Presented in Seoul in October 2010 • Specific interest of three of the core group

RMIT University©R.F.Greaves AACB Mass Spec Satellite Meeting 29

Stage 1 Planning“This project is to harmonise the measurement of

serum testosterone concentrations in clinical samples using liquid chromatography isotope-dilution tandem mass spectrometry (LCTMS) methods”

• My rules of thumb:1 KISS1. KISS

2. The better the planning the better the outcome


the better the outcome

3. Don’t rush

Stage 1 Harmonisation Goals1. To provide detailed information on the different serum testosterone

LCTMS methods used in Asian Pacific clinical biochemistryl b t ilaboratories

2. To harmonise the serum testosterone results through the use of aset of common secondary serum calibrators that have beenset of common secondary serum calibrators that have beenvalidated by a reference method

3. To harmonise reference intervals for serum testosterone ofdifferent sexes and age groups in the Asian Pacific region


Stage 1 Documents


Stage 1 Strategies

A. Formation of the Project Working Group

B. Recruitment of participating laboratories

C Documentation of serum testosterone LC TMS methods ofC. Documentation of serum testosterone LC-TMS methods of participating laboratories

D I iti l t f f St IID. Initial assessment of performance – Stage II

E. Harmonisation of accuracy performance – Stage III


F. Harmonisation of reference intervals – Stage IV

Stage 1 Resources

Literature Laboratories


Stage 2 Initial questionnaire

Question Response SummaryTestosterone standard material:Testosterone standard material:

Source 1: Lipomed,2: WEQAS, 3-4: Sigma

Purity 1: > 98.5 %, 2: 99%, 3: >98%

Isotope-labelled testosterone: D2 Testosterone

Source Cambridge Isotope Laboratories Inc.

Purity 98%

Labelling positions 1,2

Calibrator matrix Stripped plasma Foetal Bovine or stripped serum


Source 1:Sigma, 2:WEQAS, 3:Sera Care Life Sciences, 4:In-house

Stage 2 Initial questionnaire

Question Response SummaryMRM for quantitation 289 > 109 or 97MRM for quantitation 289 > 109 or 97

MRM for confirmation 289 > 109 or 97

MRM for labelled testosterone 291 > 111 or 99


Stage 2 RCPAQAP Endo Material

• Endocrine Program:Si li l l t d l l– Six linearly related levels

– Two cycles per annum– Two samples per month p p– Each level repeated twice in a cycle

• Represents expected “normal” and “pathological” patient concentrations

• Limits of performance based on biological variation data

• Target values set where practicableg p–Often with established traceability e.g. cortisol & testosterone


Stage 2 Initial assessment of lab performance

Accuracy between-batch imprecision and linearity performance will beAccuracy, between-batch imprecision and linearity performance will be evaluated via the RCPAQAP Endocrine program over a 12-month

period i.e. 2011


Stage 2 Initial assessment of lab performance

2012 Mid t


2012 Midyear report

Stage 3 Common Calibrator• 8 Labs with LC-MSMS

methods–Austria x 1–Hong Kong x 2

Melbourne x 1–Melbourne x 1–NSW x 1–Queensland x 1–Western Australia x 2

• 1 Lab with GC-MS method– NSW x 1


Stage 3 Common Calibrator


Stage 3 Biocrates calibrator


Stage 3 Common calibrator• Considerations

–Range

Level nmol/L ng/mL

1 0 035 0 01Range–Levels–Matrix

1 0.035 0.01

2 0.139 0.04

–Value assignment–Traceability

3 0.693 0.20

4 2.774 0.80–Volume of vial–Shelf life

O i l t bilit

5 10.401 3.00

6 20.803 6.00–Open vial stability–Lot to lot variation 7 34.671 10.00


Stage 3 Study protocolRun 1• Use in house calibration curve as usual – in duplicateUse in house calibration curve as usual in duplicate

• Run 7 levels of Biocrates – in duplicate

• Run 6 levels of QAP material – in duplicate

• Aliquot and freeze QAP material to use for run 2

Run 2 - How long between runs?• Use in house calibration curve as usual – in duplicate

• Run 7 levels of Biocrates – in duplicate – use fresh vials

• Run 6 levels of QAP material – in duplicate – use frozen aliquot• Run 6 levels of QAP material – in duplicate – use frozen aliquot

• Submit results for collation


Stage 3 Distributiong• Biocrates Common Calibrator

• RCPAQAP Endocrine materialRCPAQAP Endocrine material

• Human serum – 1 x male, 1 x female

• Survey review• Survey review

• Distribution November 2012


Stage 3 Confidentiality signed


Stage 3 Labs8 Labs with methods:• Hong Kong x 2Hong Kong x 2• NSW x 1 = NMI analysed by two methods

M lb 1• Melbourne x 1• Austria x 1• Queensland x 1• Western Australia x 2


Western Australia x 2

Stage 3 Certified Reference Material


NMIA = National Measurement Institute Australia

Stage 3 ResultsA. Traceability Established

– Biocrates calibrator values aligned closely with NMI targets

B. Review results– Linear regression

ANOVA performed– ANOVA performed

C. Commutability– Established for Biocrates material by comparing NMI GCMS– Established for Biocrates material by comparing NMI GCMS

method with LC-MSMS method

D. Look for significant differences in methodsg– Through questionnaires


Stage 3 Biocrates weighed-in vs NMI targetBiocrates Calibrator Set (nmol/L)Level run 1 (1) run 1 (2) run 2 (1) run 2 (2) Ave NMI Weighed

1 0.034 0.032 0.033 0.0352 0.123 0.122 0.123 0.139 1.5 Difference

40 Biocrates

Bland-Altman Passing-Bablok

3 0.664 0.681 0.670 0.688 0.676 0.6934 2.694 2.542 2.669 2.529 2.609 2.775 10.134 10.142 10.156 10.195 10.157 10.46 19.522 20.289 19.616 20.586 20.003 20.87 32 645 34 012 32 184 33 990 33 208 34 7

0.5

1.0

30

7 32.645 34.012 32.184 33.990 33.208 34.7

-0.5

0.0

Outcome10

20

Difference plot N = 7

Common calibrator package insert values compared to NMI target values

0 10 20 30 40

Mean-1.5

-1.0–Excellent agreement–Traceability established

NMI targets employed Slope : 1 043 [ 1 023 to 1 058 ]Passing-Bablok agreement test N = 7

Common calibrator package insert values compared to NMI target values

0 10 20 30 40NMI

0

Mean difference : 0.39 [ -0.129 to 0.908 ]Difference plot N = 7–NMI targets employed


Intercept : 0.0006 [ -0.0224 to 0.0131 ]Slope : 1.043 [ 1.023 to 1.058 ]

“Stockholm Hierarchy”

Level Principle1 Clinical Outcome

2A Biological variationg2B Clinician Survey3 Professional Recommendations4 Proficiency survey

AACB Mass Spec Satellite MeetingRMIT University©

y y5 State of the Art

Stage 3 Testo - Allowable LimitsBiological Variation Data ALP - RCPAQAP

• ± 0.4 up to 2.7 nmol/LBiological Variation Data (desirable specifications)S

p

• ± 15% > 2.7 nmol/L

• ALP’s based on:– monitoring

Mi i i i i i t i biTEa = (1.65 x CVa) + Bias

S- Measurand CVi CVw CVa Bias TEa

S- Testosterone 9.3 19.7 4.7 5.4 13.1

– Minimum imprecision requirements i.e. no bias– QAP is not a total error calculation

a ( )Bias < 0.25 (CVi2+CVw2)1/2


http://www.westgard.com/biodatabase1.htm

Stage 3 Common Cal – Male


Stage 3 Common Cal – Male ANOVA

Testosterone umol/LANOVAurce of Variati SS df MS F P‐value F critSample 2.256485 1 2.256485 10.92409 0.002974 4.259677Columns 16.86851 3 5.622837 27.22126 6.75E‐08 3.008787I t ti 2 494547 3 0 831516 4 025532 0 018775 3 008787

Lab 1 2 4 517.17 15.99 15.05 16.2516 27 16 53 14 8 15 7

Interaction 2.494547 3 0.831516 4.025532 0.018775 3.008787Within 4.957452 24 0.20656

Total 26.57699 31

• Samples = there is an overall16.27 16.53 14.8 15.717.01 16.08 14.81 16.1716.72 16.13 15.99 16.2118 9 17 46 16 02 15 68

Pre

• Samples = there is an overall difference between pre and post standardisation groups

• Columns = there is a difference18.9 17.46 16.02 15.68

17.90 16.85 15.76 15.15

17.7 16.41 15.00 16.0217.40 16.89 16.18 16.06Post

• Columns = there is a difference between within the labs pre and post

• Interaction = there is a difference overall when taking into account pre vs


overall when taking into account pre vs post and labs

Stage 3 Common Cal –Female

??Problem – biological variation data available is mainly based on malesg y


Stage 3 Common Cal – Female


Stage 3 Common Cal – Female ANOVA

Testosterone umol/LANOVAurce of Variati SS df MS F P‐value F critSample 0.000338 1 0.000338 0.154876 0.698541 4.413873Columns 0.006075 2 0.003038 1.393881 0.273642 3.554557Interaction 0.008325 2 0.004162 1.910134 0.176894 3.554557Within 0.039225 18 0.002179

Total 0.053963 23

Lab 1 2 50.56 0.61 0.50 54 0 6 0 67

• There was no overall difference between these three labs

• ANOVA also done separately with first

0.54 0.6 0.670.58 0.54 0.570.52 0.57 0.610.6 0.65 0 46

Pre

ANOVA also done separately with first and second run calculated as separate labs (not shown)

• no difference between pre and post

0.6 0.65 0.46

0.60 0.61 0.61

0.6 0.59 0.530.52 0.62 0.57

Post


• difference between columns and interactions

Stage 3 Common Cal Outcome• Biocrates calibrator (of testo)

–Traceable to NMI–Commutable between NMI GC-MS & LC-MSMS–Suitable for testosterone

–number of levels–concentration of levels

• Change in bias – i.e. ANOVA

• Still need to summarise the questionnaire informationStill need to summarise the questionnaire information

• Consider issues!RMIT University©2013 AACB ASM Gold Coast Australia 59

Stage 3 A common calibrator is not the complete answer


Stage 3 Questionnaire


Stage 3 Considerations for harmonisation of methodTandem Mass Spec Chromatography

S ti f i• Separation of isomers

• 1 – testosterone

• 2 – epi testosterone

• 3 – androstenedione

• 4 - DHTRMIT University©R.F.Greaves AACB Mass Spec Satellite Meeting 62

Stage 3 Considerations for harmonisation of methodIon alterations

• MRM mode – potentially hides co-elution of compounds that can cause ion suppressioncause ion suppression

• ID compensates

• Altered sensitivity• Altered sensitivity

• Ideally – remove during sample prep &/or separate Monitor 184 and 104 ion transition

RMIT University©R.F.Greaves SMS – Medical Sciences 63

prep &/or separate chromatographically

Monitor 184 and 104 ion transition

Looking aheadStage 4 REFERENCE INTERVALS (RI)

• Some MS based RI availableSome MS based RI available• Education of clinicians needed to ensure immunoassay RI

are not applied• Measurand different for MS assays• Need to develop common RINeed to develop common RI“bias is the most important performance characteristic

when using fixed limits for test interpretation”g pCallum Fraser – Biological variation: from principles to practice page 37


Looking further aheadStage 5

–BEST PRACTICE Stage 6

–ONGOING REVIEWDOCUMENT–CDC / AACB Vitamins

Working Party template

–RCPAQAP–Ongoing Patient

comparisonsg y p co pa so s–New measurands

RMIT University©R.F.Greaves SMS – Medical Sciences 65

SummaryTh l t d d t t• The example today demonstrates

1. Long term advantage of a common (traceable) calibrator2 H t k h ld f ll k t th2. How stakeholders from all areas can work together on

harmonisation initiatives3 Some of the challenges associated with standardisation /3. Some of the challenges associated with standardisation /

harmonisation4 The importance of participating in a common EQA4. The importance of participating in a common EQA5. The vital role the RCPAQAP plays in Asia-Pacific

harmonisation and standardisation initiativesharmonisation and standardisation initiatives


LCMSMS Harmonisation ConfidenceI iti l

Ex

InitialEnthusiasm Cautious

Optimismcit

Optimism

tem LC-MSMS

TroughOf

ent

Introduction Disillusion

RMIT University©R.F.Greaves AACB Mass Spec Satellite Meeting 67

t

Year1990 2000 2010

Acknowledgements Stage 3P lPeople1. Conchita Boyder2. Brian Cooke3 Ian Farrance

Organisations1. Agilent Technologies2. Biocrates3 N i l M I i3. Ian Farrance

4. Chris Fouracre5. Jan Gill 6. Dr CS Ho7 Kirsten Hoad

3. National Measurement Institute4. PM Separations5. RCPAQAP6. Our hospitals / research labs / institutes7. APFCB / AACB7. Kirsten Hoad

8. Heidi Iu9. John Joseph10. Therese Koal11. Brett McWhinney

/

y12. Lindsey MacKay13. Annabel Mitchell14. John Murby15. Pham Tuan Hai16. Michael Rennie17. Jill Tate18. Veronica Vamathevan


Photo: Foyer Zurich Kinderspital

Mass Spectrometry Harmonisation

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