Establishing Traceability and Comparability of measurement results by a limited number of well-chosen Certified Reference Materials

Transcription

1 Establishing Traceability and Comparability of measurement results by a limited number of well-chosen Certified Reference Materials Robert Kaarls Secretary CIPM, President CCQM The Future of Reference Materials Science and Innovation November 23-25, 2010, JRC IRMM Geel, Belgium 1

2 Contents Comparability and traceability Primary methods, primary calibrators and purity analysis Criteria for NMIs An efficient and effective approach: testing core capabilities and competencies Well choosen primary calibrators 2

3 Once measured, everywhere accepted requires Comparability through Traceability Metrological traceability Property of a measurement result whereby the result can be related to a reference through an unbroken chain of calibrations, each contributing to the measurement uncertainty JCGM 200:2008 (VIM 3) Traceability to the SI, or if not (yet) possible to another internationally agreed reference (hardness, ph, WHO International Units) 3

4 Traceability Traceability to the mole or other SI units Amount of substance : mol Amount fraction : mol/mol Amount concentration : mol/m 3 Mass concentration : kg/m 3 Amount content : mol/kg Mass fraction : kg/kg (or expressed in multiples or sub-multiples) and Identification of the entity (measurand/analyte) 4

5 Traceability Method dependence Measurand Defined by the method/procedure Influence quantities fixed Nevertheless in general still SI traceable Biological measurands often defined in terms of WHO reference standards and measured in terms of WHO International Units (IU) WHO reference standards defined by what it does, instead of what it is WHO and other consensus reference standards not really reproducible; thus large(r) measurement uncertainty 5

6 Traceability Potential primary methods Gravimetry Titrimetry Coulometry Calorimetry (differential scanning calorimetry) Cavity Ring Down Spectrometry Isotope Dilution Mass Spectrometry Instrumental Neutron Activation Analysis Only when the procedure is completely understood and precisely followed and staff is competent and experienced to carry out the measurement/analysis process 6

7 Traceability primary methods and primary calibrators Purity analysis» often (100% - impurities) Impurity analysis: measurement uncertainty less critical, but add uncertainty component for unknown impurities Calibration solutions Calibrators, pure compounds Certified Reference Materials Matrix CRMs Recovery factor (if correction applied, part of calibration) Method validation 7

8 Chemical measurement standards, CRMs and procedures Organic, inorganic, gas, electro-chemical, surface and bio analysis - complex molecules in a complex matrix environment - in a number of cases measurand defined on basis of what it does and not on basis of what it is ; what is the conversion factor? - definition of measurand/analyte often not understood - measurement method/procedure dependent measurand/results - from measurement dependent prescription to performance criteria - commutability - method validation - sample preparation often largest source of measurement uncertainty 8

9 Traceability and measurement uncertainty Major uncertainty components Sampling (normally not taken into account) Sample preparation (dilution, extraction, clean up, contamination, separation, etc., etc.) Homogeneity (bulk, with-in bottle and between-bottle) Stability Sample size Recovery (matrix CRM when used for calibration) Commutability Most uncertainty components are type B 9

10 Primary Calibrators (ISO 17511) 10

11 The National Metrological Infrastructure Dissemination of traceability to the SI NMI DIs Accredited Calibration labs & CRM prod. Testing and industrial/field laboratories Traceability to the SI Products and services 11

12 Traceability requirements for NMIs ultimate source of traceability (CIPM MRA) only by own primary realisation or from another recognized NMI/DI traceability can not come from a non-nmi/di (accredited or not-accredited) traceability can not come from CRMs delivered by non-nmis/dis traceability is not realized by the result in a comparison or PT scheme 12

13 Traceability NMI/DI may carry out purity analysis on commercial bought CRMs and, if CRM quality is in conformity with fit-for-purpose requirement, use these (in that case traceability comes from the NMI itself) Sub-contracting (ISO/IEC 17025)/Collaboration (ISO Guide 34) only in addition to own measurement capabilities as extra check (e.g. expensive NMR facility or a reactor for NAA) NMI responsible for assuring QS (ISO/IEC 17025) Can not lead to smaller measurement uncertainty claims than can be achieved with own capabilities 13

14 Traceability In general not to be realized by taking a consensus value obtained from a collaborative trial (a weak, costly and time consuming, and in general wrong, way of establishing traceability) Like in physics, also in chemistry the NMI should be able to establish traceability by applying one or two techniques/methods/procedures NMI has to demonstrate its competence and capabilities to assign measurement values and to deliver traceability through CRMs by participation in a limited number of well selected international comparisons The big question: How far does the light shine? 14

15 The CIPM Mutual Recognition Arrangement Published are the Calibration and Measurement Capabilities (CMCs), that are the services of the NMIs and other designated institutes, which are normally delivered to the customers * Analysing/measurement/calibration/value assignment capabilities for in-house RMs, and/or * CRM s delivered/sold to customers * Delivering assigned reference values for PT schemes Some CMCs of which 4700 chemical, 3800 ionizing radiation, physical (Appendix C) Some 450 CMCs greyed out Data Base KCDB on 15

16 CCQM Approach to increase efficiency and effectiveness of demonstrating NMI capabilities and competences CCQM IAWG, OAWG and GAWG are now trying out and implementing new approach to demonstrating the validity of claimed CMCs: Key Comparisons testing core competencies Key Comparisons of deliverables, like CRMs Key Comparisons of challenging components and matrices Pilot Study Comparisons (bench marking, research, try out, newcomers, etc.) A System to Interpret the Results of Key Comparisons to Support CMCs Based on Demonstrations of Core Capabilities (Greg Turk, NIST) 16

17 OAWG Core Competencies Purity Assessment/value assignment of Primary References: Mass fraction and associated uncertainty Identify verification Molecular weight Polarity Level of purity Value-assignment (including verification) of single and multi-component formulated solutions: Mass fraction and associated uncertainty Identify of components Molecular weight Polarity Volatility Multicomponent effects Solution matrix Selectivity of analytes of interest (verification) Extraction of analytes of interest from matrix Cleanup separation of analytes of interest from other undesirable/interfering matrix/extract components as needed Transformation: Hydrolysis or derivatization or as needed Analytical separation/specificity Value-Assignment of Analytes in Complex Mixtures: Mass fraction and uncertainty For the delivery of Measurement Services to Customers Providing Primary Calibration Reference Services Providing Accuracy Control Reference Services By courtesy of Willie May and Reenie Parris - NIST 17

18 Core Capabilities for Inorganic Analysis Contamination control and correction Sample dissolution and preparation ICP-MS ICP-OES Graphite furnace AA Flame AA Ion Chromatography X-ray Fluorescence Neutron Activation Analysis By courtesy of G. Turk NIST and M. Sargent - LGC 18

19 Sub-Capabilities Inorganic Analysis Contamination control and correction Clean room operation High purity water and acid Blank correction procedures Sample dissolution and preparation Routine organic matrices Routine inorganic matrices Refractory matrices Flammable matrices Non-reactive matrices (i.e. plastics) Volatile element containment Pre-concentration Matrix separation Species separation 19

20 CCQM Gas Analysis WG approach to testing NMI s claimed capabilities and competences Retrospective approach based on results of prior comparisons and tabled CMCs Identified sets of core species as good predictors of competence to perform measurements of nonreactive species NMIs have to participate in a number of KCs before CMC claims can be considered Based on good results, a broader range of analytes and concentrations can become accepted More time will be devoted to challenging reactive species 20

21 FIELDS OF ACTIVITIES 1.Preparation and certification of Reference Materials The CMQ has prepared and certified 86 Reference Materials such as: Metals and anions in aqueous matrixes Heavy metals in wines. Under development processes, there are Reference Materials of Quinolones in Salmon and Pork and heavy metals in sea-food. Several Reference samples have been prepared for Proficiency Tests in Salmon, wines and organic solutions. By courtesy of CMQ - Chile 21

22 CRMs for Nutrients and Contaminants in Food Examples of Food-matrix Standard Reference Materials by Sector By courtesy of NIST Every food can be placed in one of these 9 sub-triangles according to its % protein, % fat, and % carbohydrate coordinates. Most food analysis labs provide analyses for a similar set of analytes but in a wide range of food types (matrices) Matrix differences and concentration differences are the primary measurement challenges. By providing SRMs certified for these common food analytes in each of the major sections of the food triangle, NIST covers most of the field of CRMs needed for the validation of these measurements of foods. 22

23 Impact: A model for Primary Calibrator Comparisons establishing, demonstrating and delivering traceability 1000 Digoxin CCQM-P20.f (2007/2008) M o le c u la r W e ig h t ( S tru ctu ra l C o m p le xity ) Chlorpyrifos Aldrin PCBs Nonachlor OCs Estradiol Atrazine Oxytetracycline Folic Acid CCQM-P20.e (2006/2007) Theophylline CMC Analytes CCQM-P20 CCQM-K55a,b HFTLS for CCQM-K55a 0 PAHs Xylene VOCs -8,0-6,0-4,0-2,0 0,0 2,0 4,0 - Log K OW ( Polarity ) Ethanol Creatinine HFTLS for CCQM-K55c HFTLS for CCQM-K55b 23

24 Bureau International des Poids et Mesures Organic Analysis Programme - April 2007 Characterization of CCQM-P20.e Study Materials Pilot study results Ralf Josephs, Steven Westwood, Robert Wielgosz, Adeline Daireaux 24

25 CCQM-P20.e Theophylline content of CCQM-P20.e Gravimetric Reference Value = ± 1.5 mg/g Mean = mg/g (SE = 0.66 mg/g) Weighted Mean = mg/g (weighted SE = 0.35 mg/g) 25 Mass fraction (mg/g) QNMR (init.) CSIR QNMR (corr.) NIST USP (Rel.) NMIA LGC BIPM CENAM USP (Assay) NIM DMSc NMIT BAM NMIJ

26 Reference Measurement Systems for Peptides and Proteins Biological Activity (IU) and Amount (SI) Relative Molecular Mass Diagnostic: Growth hormone deficiency International Reference Reagent 3.1 µg/ampoule Therapeutic: Carbohydrate Metabolism Control 1 st International Standard 26 IU/mg Blood pressure regulation Angiotensin Insulin IGF Theophylline K(ow) 26

27 BIPM and the Mutual Recognition Arrangement CIPM-MRA Technical basis for: -Determination of the degree of equivalence of measurement standards -Mutual recognition of calibration and measurement certificates By courtesy of the BIPM 27

28 BIPM and the Mutual Recognition Arrangement Key Comparisons Calibration and Measurement Capabilities 28

29 Mechanisms for measurement service delivery: CRMs 29

30 Analyte Information about Material Matrix Material Name and/or ID # Estimated * Availability (months, as of Jan 2004) cholesterol cholesterol GBW09203b 60 cholesterol cholesterol SRM 911b 21 - Producer - Country - Website - Address - Phone Number - Fax Number Contact Information NRCCRM, China Tel: Fax: crmservice@nrccrm.com.cn Reference Materials Commutability Study Information and/or Citations Primary calibrator for higher order reference methods NIST, USA Primary calibrator for higher order reference methods srminfo@nist.gov Tel:(301) Fax: (301) cholesterol human serum JCCRM cholesterol cholesterol human serum (frozen) human serum (lyophilized) SRM 1951b 60 SRM 1952a 60 HECTEF, Japan Tel: Fax: NIST, USA Material prepared following NCCLS Document C37-A srminfo@nist.gov "Preparation and Validation of Commutable Tel:(301) Frozen Human Serum Pools as Secondary Fax: (301) Reference Materials for Cholesterol Measurement Procedures; Approved Guideline" Method used for certification: Anal Chem 61, (1989) NIST, USA srminfo@nist.gov Tel:(301) Fax: (301) cholesterol human serum (lyophilized) SRM 968c 38 NIST, USA srminfo@nist.gov Tel:(301) Fax: (301) cholesterol human serum (lyophilized) SRM909b 60 NIST,USA srminfo@nist.gov Tel:(301) Fax: (301)

31 Comparability Assessment for Potassium in Human Serum CRMs on JCTLM List I: Ratio Display Measured / Certified Value SRM 956a Level-3 JCCRM L SRM 909 Level-1 SRM 956a Level-2 JCCRM M JCCRM H SRM 956a Level-1 SRM 909 Level-2 95% CI Certificate Campaign 1 Campaign 2 Listed CRMs are all comparable Potassium in Human Serum CRMs on provisional JCTLM List 1 were assessed for comparability by a single laboratory using a reference measurement procedure under repeatability conditions. The horizontal axis reports the CRMs evaluated. The vertical axis reports the ratio between the measured and certified values of each CRM, Xi/Ci. 31

32 CRM comparability studies 32

33 Market needs for CRMs - essential for realizing global comparability through traceability - need for primary calibration solutions and primary pure materials, calibrators - shortage of variety of CRMs ( different analytes in different matrix with different concentrations) - lack on demonstrated metrological traceability (accredited CRM producers in compliance with ISO/IEC and ISO Guide 34) - necessity for international cooperation in CRM production and certification - better traceability faster and cheaper CRMproduction 33

34 Conclusion - Global comparability requires metrological traceability - Reliable, traceable calibration solutions, primary calibrators and CRMs are essential - NMIs capabilities have to be demonstrated in an efficient and effective way - Delivering traceability has to be done in an efficient and effective way - Comparability and traceability of CRMs has to be demonstrated by comparisons - International recognition is essential (BIPM - Inter-Governmental Treaty Organisation; CIPM MRA) 34

35 Thank you 35