Interlaboratory validation studies, analytical

Several overall conclusions can be drawn based on the statistical evaluation of the data submitted by the participants of the DR CALUX intra-and interlaboratory validation study. First, differences in expertise between the laboratories are apparent based on the results for the calibration curves (both for the curves as provided by the coordinator and for the curves that were prepared by the participants) and on the differences in individual measurement variability. Second, the average results, over all participants, are very close to the true concentration, expressed in DR CALUX 2,3,7,8-TCDD TEQs for the analytical samples. Furthermore, the interlaboratory variation for the different sample types can be regarded as estimates for the method variability. The analytical method variability is estimated to be 10.5% for analytical samples and 22.0% for sediment extracts. Finally, responses appear dependent on the dilution of the final solution to be measured. This is hypothesized to be due to differences in dose-effect curves for different dioxin responsive element-active substances. For 2,3,7,8-TCDD, this effect is not observed. Overall, based on bioassay characteristics presented here and harmonized quality criteria published elsewhere (Behnisch et al., 2001a), the DR CALUX bioassay is regarded as an accurate and reliable tool for intensive monitoring of coastal sediments. 

Briefly, to assure quality assurance and quality control, samples are analyzed using standard analytical procedures. A continuing program of analytical laboratory quality control verifies data quality and involves participation in interlaboratory crosschecks, and replicate sampling and analysis. When applicable, it is advisable, even insisted upon by the EPA, that analytical labs be certified to complete the analysis requested. However, in many cases, time constraints often do not allow for sufficient method validation. Many researchers have experienced the consequences of invalid methods and realized that the amount of time and resources required to solve problems discovered later exceeds what would have been expended initially if the validation studies had been performed properly. 

Use of Validated Methods In-Home Versus Interlaboratory Validation Wherever possible or practically achievable, a laboratory should use methods which have been fully validated through a collaborative trial, also called interlaboratory study or method performance study. Validation in collaborative studies is required for any new analytical method before it can be published as a standard method (see below). However, single-laboratory validation is a valuable source of data usable to demonstrate the fitness for purpose of an analytical method. In-house validation is of particular interest in cases where it is inconvenient or impossible for a laboratory to enter into or to organize itself a collaborative study [4,5]. 

Interlaboratory Quality Control. In addition to the mandatory quality control practices just outlined, the laboratory is encouraged to participate in interlaboratory programs such as relevant performance evaluation (PE) studies, analysis of standard reference materials, and split sample analyses. Participation in interlaboratory analytical method validation studies is also encouraged. 

We have every reason to consider the estimation of measurement uncertainty in an analytical procedure followed by the judgement of compliance with a target uncertainty value as a kind of validation. This is in full agreement with ISO 17025 that points to several ways of validation, among them systematic assessment of the factors influencing the result and assessment of the uncertainty of the results... [31]. In line with this is also a statistical modelling approach to the validation process that has recently been developed and exemplified as applied to in-house [32] and interlaboratory [33] validation studies. 

Since its beginning in 1884, AOAC INTERNATIONAL has been truly dedicated to the validation of analytical methods through trials in multiple laboratories. An early undertaking of AOAC is still its most important business supporting the use of analytical methods used in multiple laboratories through validation by interlaboratory studies. 

Comparison with a currently accepted compendium method is another validation approach and is frequently used in industrial research laboratories. This approach uses results from a currently accepted (analytical) method as verification of the new method s results. Agreement between results initially suggests validation. However, disagreement could cast doubts on the acceptability of the new method or may suggest that the currently accepted method is invalid. Validation of compendial methods has been addressed by the USP Chapter (1225) [68]. Interlaboratory collaborative studies are discussed in Chp. 8.4.2. 

Tranffier of analytical method methodology. Continuation of method validation by (costly and lengthy) interlaboratory collaborative studies (ruggedness) statistical comparison of the validation results (e.g. for HPLC methods cfr. ref. [70]). 

Validation of a new analytical method is typically done at two levels. The first is the level of prevalidation, aiming at fixing the scope of the validation. The second level is an extensive, full validation performed through a collaborative trial or interlaboratory study. The objective of full validation, involving a minimum number of laboratories, is to demonstrate that the method performs as was stated after the prevalidation. 

If data are normally distributed, the mean and standard deviation are the best description possible of the data. Modern analytical chemistry is often automated to the extent that data are not individually scrutinized, and parameters of the data are simply calculated with a hope that the assumption of normality is valid. Unfortunately, the odd bad apple, or outlier, can spoil the calculations. Data, even without errors, may be more or less normal but with more extreme values than would be expected. These are known has heavy-tailed distributions, and the values at the extremes are called outliers. In interlaboratory studies designed to assess proficiency, the data often have outliers, which cannot be rejected out of hand. It would be a misrepresentation for a proficiency testing body to announce that all its laboratories give results within 2 standard deviations (except the ones that were excluded from the calculations). 

Improvement schemes can be defined as a succession of individual interlaboratory studies in which several laboratories analyse the same test samples for the same characteristics (usually the content of an analyte), following a similar protocol to validate each individual step of their own analytical method (Quevauviller, 1999a). They enable laboratories to develop and validate all steps of new or existing analytical procedure(s) in adequately organised successive exercises which may be considered as preliminary studies for laboratory or method performance studies or certification of RMs (Griepink and Stoeppler, 1992 Quevauviller, 1998b). Such programmes are particularly valuable in the case of speciation studies since the analytical procedures include several complex and critical steps. 

In view of these issues, we have over several years undertaken a substantial research programme to develop definitive methods appropriate for in-house certification of matrix RMs, particularly for analytes at trace levels. These definitive measurement methods, most of which use isotope dilution mass spectrometry (IDMS), been the subject of extensive validation, including CCQM key comparisons and pilot studies involving other national measurement institutes. Hence, we are now able to augment interlaboratory data with data obtained at LGC using these very accurate measurements. We have also... 

Attempts to correlate analytical performance with other seemingly indicative laboratory characteristics, such as participation in proficiency testing schemes, regular use of certified RMs, number of years of experience and number of samples analysed per year were all equally unsuccessful. Therefore, in the absence of any simple and obvious means of identifying and preselecting only reliable laboratories as participants in certification studies, an investigation was undertaken of the validity of adopting the consensus mean (after outlier elimination) from an interlaboratory study as a certified value. 

Full validation of an analytical method usually comprises an examination of its characteristics in interlaboratory method performance studies. However, before a method is subjected to validation by collaborative studies, the method must be validated by a single laboratory, usually by the laboratory that developed or modified this particular measurement procedure. Method validation can be described as the set of tests used to establish and document the performance characteristics of a method and against which it may be judged, thereby demonstrating that the method is fit for a particular analytical purpose. 

What do validated methods mean to the laboratory Why use methods that have been performance-characterized through interlaboratory study validation Such methods give the analyst increased confidence in the results of this analysis. In addition, the user of analytical data, who frequently may not be the analyst or... 

An acceptable interlaboratory study should be designed to support the intended scope of the method and to validate the performance across that scope. The number and type of materials sent to the collaborators is very important Material is defined as a matrix/analyte combination, the aim being to have five ma-... 

CRMs to finalise the method development, to validate analytical procedures and finally control in time the accuracy of procedures, are rare and valuable materials, in particular matrix CRMs. They should tell the analyst how his entire measurement procedure is performing. He will receive information on precision as well as on trueness. CRMs are primarily developed to check for trueness, which is the most difficult property to verify. Precision can be tested on RMs or can be estimated from published data e.g. the performance required by a standard method, whereas the evaluation of trueness is possible only with external help a CRM or a properly organised interlaboratory study. Having a CRM allows one to perform the verification of trueness whenever the operator wants it. The analyst should never forget that only when accurate results (precise and true) are achieved, comparability in space and over time is guaranteed. But to exploit to a maximum the information on trueness delivered by the CRM, the precision must also be sufficient and verified. 

Techniques developed for the determination of selenite and selenate involve a succession of several analytical steps (e.g. reduction, separation, detection) which are often far from being validated. In addition, the knowledge related to the stability of the species is still very scarce. A project has hence been launched within the BCR programme with the aim to evaluate the stability of Se-species in solution [42] this feasibility study has been continued by an interlaboratory study for the evaluation of method performance [43]. Both investigations were designed to improve the state-of-the-art of Se-speciation prior to the tentative certification of solution candidate reference materials as described in this section. As a follow-up, artificial freshwater solutions containing inorganic Se-species were prepared (RMs 602 and 603) [40,41]. 

Improvement schemes can be defined as a succession of individual interlaboratory studies in which several laboratories analyse the same test samples for the same characteristics (usually the content of an analyte), following a similar protocol, to validate each individual step of their own analytical method in order to eliminate all sources of systematic errors [5]... 

---