Method Validation Revisited: Its Role in Traceability of Results Wolfhard Wegscheider Institute for General and Analytical Chemistry University of Leoben, AUSTRIA

Standard view of the relation between uncertainty and validation MeasurementuncertaintyMeasurementuncertainty othereffects biasprecision from SLR Ellison 1999

Traditional roles of method validation Establish performance characteristics –Linearity –Limits of detection/determination –Precision: repeatability, intermediate reproducibility –Effect of concomitants Present data for approval of method Produce control limits for everyday operation

should What should be the role of validation ? As analytical chemistry is about making decisions validation should support the decision making process results limit

Traditional role of traceability Provide a firm and identical base of units worldwide Supply this base in a manner stable in time Underpin the hierarchy of measurements/procedures/laboratories.....

Requirements of customer Convert to uncertainty Apportion to the different steps Express as figures of merit Specify validation plan Validate Compute figures of merit Estimate factual uncertainty Accept/reject contract Do analyses Report to customerReport results Validation starts out from the customer´s needs

Two key components to traceability:

Uncertainty of a standard: Identity Purity Preparation

Influence of uncertainty of standards in calibration NO uncertainty from standard With uncertainty from standard and dilution M. Rösslein, EMPA2001

Two (extreme) ways to define the measurand / analyte A) Careful and complete description of circumstances: –(exactly) what species –What (kind of) samples/concomitants –Which environmental conditions (p, T) B) Measure as specified and give the analyte a name

A general model of measurement and validation in chemistry huge and unknown for N results: somewhat smaller, but unknown

A general model of measurement and validation in chemistry After validation: small and accessible from precision data identified effects on result

Two extreme ways to define the measurand /analyte: MODEL 1 A) Measure as specified and give the analyte a name: Accessible through interlab comparisons The „new“ analyte

Two extreme ways to define the measurand /analyte: MODEL 2 Very small part of uncertainty The „old“ analyte well defined B) Careful and complete description of circumstances:

The Measurement of pH IUPAC Working Party on pH Notational definition: Operational definition:

Operational Definition of pH Debye-Hückel formalism with Bates- Guggenheim convention (only) 5 primary buffers 3 < pH < 10 I < 0.1 mol/l Aqueous solution

uncertainty (a.u.) a b c bottom-up real + u def avoid + u def + u corr Uncertainty of standard methods: experience in practice

Redesigning validation studies: what has been missing so far ? Establish the quality of the standards Complete coverage of scope OR clear redefinition of the analyte Anchored in the requirements of the customer

 Traceability of results and reference values is a central issue in modern laboratory operation. It is not an end in itself, but serves the purpose of achieving a reliable result.  Traceability of results can only be claimed if results are accompanied by an uncertainty statement based on traceability of all references, chemical and physical, as well as on procedural contributions to uncertainty.  A result must be "fit for purpose", thus estimation of measurement uncertainty from uncertainties of references and procedures is added value for laboratories and simple when guidelines are followed.