Inter-laboratory study

The organization of and participation in inter-laboratory studies are essential for the advance of science and are therefore to be encouraged. 

1 Qudel, C.R., Leveque, N., De BoHe, W., and Ponzevera, E. (2007) Final report on CCQM-P48 uranium isotope ratio 

DePaolo, D.J., McCulloch, M.T., and Wen, T. (1981) Precise determination of Sm/Nd ratios, Sm and Nd isotopic abundances in standard solutions. Geochim. Cosmochim. Acta, 45, 2311-2323. 

3 Hibbert, D.B. (2007) Quality Assurance for the Analytical Chemistry Laboratory, Oxford University Press, Oxford. 

4 Bureau International des Poids et Mesures (BIPM) (2008) International Vocabulary of Metrology - Basic and General Concepts and Associated Terms (VIM), 3rd edn., )CGM 200 2008, http // www.bipm.org/en/publications/guides/ vim.html (last accessed 23 December 2011) also published as ISO/IEC Guide 99-12 2007, International Organization for Standardization, Geneva. 

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NIST has also used results obtained from inter-laboratory studies as an additional set of results in the two or more methods approach (mode 2 in Table 3.13). For example for the recent value assignment for PCBs and pesticides in SRM 1944, the mean of results from 19 laboratories participating in an inter-laboratory comparison exercise was used as an additional set of data in the determination of the certified values. Similar inter-laboratory study results were also included in the value assignment of PAHs, PCBs, and pesticides for two recently issued mussel tissue materials, SRM 2977 and SRM 2978. 

Frozen reference materials have been produced by NIST (Wise et al. 1993). These materials do not have the disadvantages of the oils or freeze-dried materials, but are more difficult to transport. Obviously they have to be kept deep-frozen during transport, which makes their use rather expensive. Since the early 1990 s a new approach in this field has been introduced. This concerned the use of wet, sterilized fish and shellfish samples. These samples, packed in glass jars or in tins, were firstly used in the QUASIMEME program as reference materials for inter-laboratory studies (de Boer 1997). Later, when it appeared that the stability was maintained for longer periods, tests for organic contaminants based on this principle were also prepared. 

The laboratory of the European Pharmacopoeia applies the method specific approach (inter-laboratory study) as has been previously described (Technical Guide for the Elaboration of Monographs 1996). 

The NADA method approval process consists of three phases (1) method development by the sponsor and generation of information to establish that the method satisfies acceptability criteria (2) FDA review of the sponsor s data to determine suitability of the method and (3) the method trial , an inter-laboratory study, which determine whether the method meets performance criteria when used in multiple laboratories. The inter-laboratory method trial procedure provides an indication of a method s ability to be used as a practicable and reliable regulatory tool. Sponsors are urged to develop methods that are mgged and exceed rather than meet the minimal standards of acceptability. Those methods that appear marginally acceptable after review often do not pass the inter-laboratory method trial. 

The methods EN 1528 1996 and EN 12393 1998 comprise a range of old multiresidue methods of equal status, which are widely accepted throughout Europe. These are, e.g., the Luke method and the German Deutsche Forschungsgemeinschaft (DFG) methods S8 and S19 ° (all based on extraction with acetone), the Association of Official Analytical Chemists (AOAC) method 970.52 (using acetonitrile extraction and liquid-liquid partition combined with Horisil column cleanup) and the Dutch ethyl acetate extraction combined with GPC. All methods have been subjected to inter-laboratory studies, although not with all pesticide/matrix combinations, which would be impossible to achieve. 

Because of the small number of laboratories involved, validation of UK methods by inter-laboratory study has become impractical in most cases. Even where it is practical, it is usually impossible to validate all pesticide-matrix combinations. Moreover, single-laboratory validation data will have to be generated. Therefore, the CSL guidelines are one of the first that strictly focus on requirements of single-laboratory validation. Some examples of minimum requirements are given in Table 8. Additionally, these guidelines emphasize some other important aspects of validation and contain some new ideas. 

Even if most examples and procedures presented apply to in-house validation, the procedure does not distinguish between validations conducted in a single laboratory and those carried out within inter-laboratory method performance studies. A preference for inter-laboratory studies can be concluded from the statement that laboratories should always give priority to methods which have been tested in method performance studies. Within the procedure a profound overview of different categories of analytical methods according to the available documentation and previous external validation is given. For example, if a method is externally validated in a method performance study, it should be tested for trueness and precision only. On the other hand, a full validation is recommended for those methods which are published in the scientific literature without complete presentation of essential performance characteristics (Table 9). 

In summary, official German analytical methods for pesticide residues are always validated in several laboratories. These inter-laboratory studies avoid the acceptance of methods which cannot readily be reproduced in further laboratories and they do improve the ruggedness of analytical procedures applied. The recently introduced calibration with standards in matrix improves the trueness of the reported recovery data. Other aspects of validation (sample processing, analyte stability, extraction efficiency) are not considered. 

In Europe, very different concepts of method validation are in use. The extent of validation depends upon legal requirements (e.g., for enforcement methods provided by the applicant), upon the required level of acceptance (e.g., for CEN methods) and upon national resources. Undoubtedly, the best method validation is performed with the help of inter-laboratory studies of performance, but such studies can be uneconomic, too slow to reach completion or restricted in scope. 

The workhorses in national monitoring programs are multi-residue methods. Any official method collection of any EU Member State contains at least one multi-residue method. For multi-analyte and/or multi-matrix methods, it is likely to be impractical to validate a method for all possible combinations of analyte, concentration and type of sample matrix that may be encountered in subsequent use of the method. Therefore, initial validation should incorporate as many of the target analytes and matrices as practicable. For practical reasons this validation and the evaluation of other methods with limited scope often cannot be conducted in inter-laboratory studies. Other concepts based on independent laboratory validation or validation in a single laboratory have been developed and can provide a practical and cost-effective alternative (or intermediate) approach. 

Inter-laboratory study Three laboratories required One independent Recommended but not... 

Consequently, it was proposed to define (Burns et al. [2005]) Robustness of an analytical procedure is the property that indicates insensitivity against changes of known operational parameters on the results of the method and hence its suitability for its defined purpose and Ruggedness of an analytical procedure is the property that indicates insensitivity against changes of known operational variables and in addition any variations (not discovered in intra-laboratory experiments) which may be revealed by inter-laboratory studies (Burns et al. [2005]). 

Property of an analytical procedure that indicates insensitivity against changes of known operational variables and in addition any variations (not discovered in intra-laboratory experiments) which may be revealed by inter-laboratory studies. 

Alford Stevens et al. [49] have reported on an inter-laboratory study of the determination of polychlorinated biphenyls in environmental sediments. Electron capture gas chromatography and mass spectrometry were used to identify and determine polychlorinated biphenyls. For electron capture, an overall standard deviation of 30% was achieved while mass spectrometry gave 38%. 

Lee and Chau [66] have discussed the development and certification of a sediment reference material for total polychlorobiphenyls. Alford Stevens et al. [49] in an inter-laboratory study on the determination of polychlorobiphenyls in environmentally contaminated sediments showed the mean relative standard deviation of measured polychlorobiphenyl concentrations was 34%, despite efforts to eliminate procedural variations. Eganhouse and Gosset [67] have discussed the sources and magnitude of bias associated with the determination of polychlorobiphenyls in environmental sediments. Heilman [30] studied the adsorption and desorption of polychlorobiphenyl on sediments. 

At the same time. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) evaluated FETAX methodology based on the inter-laboratory studies and published a review document in 2000 (5). The expert panel concluded that FETAX was not sufficiently validated for regulatory use due to the intra- and inter-laboratory variability (6). Nonetheless, the assay was developed in our laboratory for use as a predictive screening assay. 

The use of MAS was not retained as the predictivity was not shown to be different with or without MAS in the inter-laboratory study (see Note 2). 

An inter-laboratory study to determine benzoie acid in orange juices was reported, where a Hamilton PRP-1 column and a mobile phase mixture of 4 + 6 of aeetonitrile / phosphate buffer was used [36]. In this work, the juices were fortified with 0.5-10 ppm of benzoic acid. Statistical analysis of the results showed a relative reproducibility between laboratories ranged in the range of 6.92% to 15.97% for juice fortified with 1-10 ppm and 27.90% for juice fortified with 0.5 ppm. Mean recoveries ranged from 94.5% to 114%. 

Precision Repeatability Ruggedness Reproducibility Sample prep replication Injection replication Factorial designs Intra-laboratory study Inter-laboratory study... 

Hund, E, Massart, D L, and Smeyers-Verbeke, J (2000), Inter-laboratory studies in analytical chemistry. Analytica Chimica Acta, 423, 145-65. 

After many years of debate and discussion, there is now an international consensus about the statistical approach and method to be employed in full collaborative trials This topic is discussed further in Section 9.5. The lUPAC protocol referred to above requires the analysis of duplicate test samples of the same material (a minimum of five materials or, exceptionally, three) in eight or more laboratories. However, there are many occasions where inter-laboratory studies are needed which, for various reasons, cannot achieve the prescribed criteria. In instances where the lUPAC criteria cannot be achieved, it is recommended that the Youden Matched Pairs procedure is used. The statistics of the method have been recently updated and a new procedure described. 

The NARL inter laboratory study program is a proficiency testing scheme currently covering pesticide residues (in animal fats, soil, fruit and vegetables), pollution by petroleum products (in soil and water) and illicit drug analysis (heroin, cocaine, amphetamines and LSD). The objectives of the NARL studies are as follows ... 

The factor 2I/Z is based on the fact that r and R are related to the difference between two measurement results. For distributions which are approximately normal and in the case of not too small a number of measurements, the factor f does not vary much from 2 and one can use the approximate value of 2.8 for f-2I/2. Because in practice the true repeatability and reproducibility standard deviations are not known, they are replaced with estimated values sr and sR from the inter-laboratory study and one obtains then ... 

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