Commutable reference material

Primary calibrators, indeed all calibrators, must be commutable that is, they must behave during measurement in an identical manner to the native analyte material being measured. Matrix reference materials made by mixing a pure reference material with the components of the matrix are unlikely to be entirely commutable, and for this reason some authorities (EURACHEM for one [EURACHEM and CITAC 2002]) advise against using matrix-matched CRMs for calibration, recommending instead their use to establish recoveries, after calibration by a pure reference standard. 

A calibration hierarchy must be defined to allow metrological traceability, preferably to a unit of the International System of Units (SI). Traceability involves plugging into a reference measurement system of reference procedures and commutable calibration materials. 

There are two major reasons why a traceability chain may be broken and trueness lost due to the introduction of bias insufficient commutability of a calibration material and non-specificity of a measurement procedure. The effect of these separate properties are often indiscriminately lumped together as matrix effect . Commutability refers to the ability of a material, here a calibrator, to show the same relationships between results from a set of procedures as given by routine samples [16, 17]. Analytical specificity refers to the ability of a measurement procedure to measure solely that quantity which it purports to examine [16, 18]. Discrepancies between results of a reference procedure and a routine procedure applied to routine samples are often caused by non-specificity of the routine procedure. The use of a set of human samples as a manufacturer s calibrator to eliminate so-called matrix effects should only be accepted if the relationship between the results from reference and routine procedures is sufficiently constant to allow explicit correction with consequent increased uncertainty of assigned values. 

NCCLS (1999) Preparation and validation of commutable frozen human serum pools as secondary reference materials for cholesterol measurement procedures. NCCLS, Wayne, Pa. NCCLS document C37-A... 

A systematic procedure for evaluating the commutability (horizontal traceability or scope) of matrix reference materials has been evaluated... 

For a reference system to be capable of standardizing the results of different assays of a given en2yme activity, some conditions must be satisfied. First, the reference procedure used to assign the value of the reference material and the routine method(s) to be calibrated must have identical specificities for the analyte enzyme (i.e., for the specific isoenzyme or isoform under study). Second, the properties of the calibrator material must be the same as or closely similar to those of the analyte enzyme in its natural matrix, typically serum (i.e., the material must be commutable with human serum samples for that particular method). 

In order to validate the commutability of the DGKC control materials it was necessary to perform split sample measurements with patient samples using the test kit in parallel to the IDMS reference procedure for progesterone. The investigation revealed for both the patient sera and the ring trial results a considerable bias in relation to the reference procedure at low progesterone concentrations. (Fig. 7). The reason for the bad performance of the test was obviously a lack of specificity rather than a lack of commutability of the control materials. At even lower progesterone concentrations the bias increased up to 1000%. It should be noted that the kit manufacturer did unfortunately not issue any lower limit of determination for his measurement procedure. 

Manufacturers of diagnostic test kits sometimes argue that a lack of commutability of control materials and their inherent matrix effects are responsible for the deviations of routine results with respect to reference procedure values. Very often it is stated that the results obtained in patient samples are nevertheless true. Comparative measurements (not demonstrated here) reveal that the performance of many tests is even worse when they are evaluated by the use of patient samples. 

An aspect of matrix RMs which is of considerable importance is the question of commutability or horizontal traceability. This refers to the scope of the materials, i.e. the extent to which a matrix RM of a particular composition may reliably be used to evaluate a measurement procedure that is applied to a routine test sample of a different composition. The differences in composition between a reference matrix and a routine test sample matrix must not cause the two materials to behave differently when a particular analytical method is applied. At present, the extent to which this is true is largely a matter of expert judgement based on knowledge of the measurement application. A better and more systematic understanding of the factors affecting horizontal traceability will enable users to select appropriate matrix RMs more reliably and producers to target their production activities more efficiently. 

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