Collaborative Studies

As part of a collaborative study of a new method for determining the amount of total cholesterol in blood, two samples were sent to ten analysts with instructions to analyze each sample one time. The following results, in milligrams of total cholesterol per 100 mb of serum, were obtained... 

An analysis of variance can be extended to systems involving more than a single variable. For example, a two-way ANOVA can be used in a collaborative study to determine the importance to an analytical method of both the analyst and the instrumentation used. The treatment of multivariable ANOVA is beyond the scope of this text, but is covered in several of the texts listed as suggested readings at the end of the chapter. 

An analysis of nearly 10,000 collaborative studies suggests that a reasonable estimate for a method s reproducibility is... 

What is the estimated relative standard deviation for the results of a collaborative study in which the sample is pure analyte (100% w/w analyte) Repeat for the case in which the analyte s concentration is 0.1% w/w. 

Thus, we expect that approximately 67% of the participants in the collaborative study (+I0) will report the analyte s concentration within the range of 98% w/w to 102% w/w. When the analyte s concentration is 0.1% w/w (C = 0.001), the estimated percent relative standard deviation is... 

Of course, equation 14.26 only provides an estimate of the variability in results submitted by those participating in a collaborative study. A relative standard deviation that is within one-half to twice the estimated value suggests that the method performs acceptably when used by analysts in different laboratories. The percent relative standard deviation for a single analyst should be one-half to two-thirds that for the variability between analysts. 

Preliminary report on "Collaborative Study on the Proposed International Standard for Somatropin," National Institute for Biological Standards and Control, London, Dec. 21, 1992. 

J. Ashby and co-eds., Progress in Mutation Kesearch, Vol. 5, Evaluation of Short-Term Testsfor Carcinogens Teport of the International Programme on Chemical Safety s Collaborative Study In VitroMssays, Elsevier, Amsterdam, The Netherlands, 1985, pp. 117—174. 

MacDonald, H., and Tobin, J. O. H. (1978). Congenital cytomegalovitiis infection A collaborative study on epidemiological, clinical and laboratory findings. Dev. Med. Child Neurol. 20, 271-282. 

G. M. Frame, A collaborative study of 209 PCB congeners and 6 Aroclor s on 20 different HRGC columns. Part 2. Semi-quantitative Aroclor congener distributions . Anal. Chem. 70 714-722(1997). 

Mitchell LR. 1976. Collaborative study of the determination of endosulfan, endosulfan sulfate, tetrasul, and tetradifon residues in fresh fruits and vegetables. J Assoc Off Anal Chem 59 209-212. 

Beer Samples. The beer samples were examined as part of the American Society of Brewing Chemists (ASBC) and Association of Official Analytical Chemists (AOAC) collaborative studies of NDMA in beer. Duplicate samples were analyzed by the column extraction procedure and the ASBC distillation procedure (35). The AOAC procedure (36) was similar, except that a larger sample (50 vs. 25 g) was examined and sulfamic acid was added to minimize artifactual formation of nitrosamines. Both methods utilize N-nitrosodipropylamine (NDPA) as an internal standard. 

For the AOAC beer samples, a 2 m x 2 mm glass column packed with 8.57o Carbowax 20 M + 0.857, NaOH on 100/120 mesh Chromosorb G was used at 130 C and a helium flow rate of 20 cc/min. Retention times of NDMA and NDPA were 4.5 and 12.2 min, respectively. For the ASBC collaborative study, a 1 m x 2 mm glass column containing 67, Carbowax 20 M-TPA on 100/120 mesh Chromosorb G was operated at 90 C with 20 cc/min helium flow rate. Retention times were 3.6 and 11.3 min for NDMA and NDPA, respectively. For determination of nitrosamines in amines, a 2 m X 2 mm, 107, Carbowax 20 M-TPA on 100/120 mesh Chromosorb G column was operated at 190 C with a carrier gas flow rate of 20 cc/min. Retention times were NPYR, 6.6 min NMOR, 7.4 min. 

Figure 1 shows narrow range high resolution scans of the molecular ion region of NDMA, recorded near the maximum of the GC peaks, present in one of the beer samples prepared in the AOAC collaborative study. The peak at m/z 74.0480 represents approximately 0.15 ng of NDMA injected on the column, corresponding to a concentration of 0.6 yg/kg of beer. Use of high resolution MS permitted confirmation of the identity and amount of nitrosamine without additional cleanup of the concentrate prepared by the AOAC method. Sample quantity requirements were comparable to those of the TEA. 

Lee, J., Durst, R.W., and Wrolstad, R.E., Determination of total monomeric antho-cyanin pigment content of fruit juices, beverages, natural colorants, and wines by the pH differential method collaborative study, J. AOAC Int., 88, 1269, 2005. 

It is not strictly required to use the same attributes in each data set. This allows the comparison of independent QDA results obtained by different laboratories or development departments in collaborative studies. Also within a single panel, individual panellists may work with personal lists of attributes. When the sensory attributes are chosen freely by the individual panellist one speaks of Free Choice Profiling. When each panellist uses such a personal list of attributes, it is likely that... 

In those cases where there are any doubts about the feasibility of producing a sufficiently homogeneous and stable reference material, a feasibility study might be needed. For this study, an extra amount of material is needed. Questions regarding the best way of preparing the sample, the stability of the material, or the fitness for purpose might justify the inclusion of a feasibility study in the project. In the BCR projects, it is common practice to have a feasibility study, which usually has as the sole purpose of assessing the performance of the laboratories in the collaborative study in relation to the certification of the reference material. The feasibility study allows the participants to fine-tune their equipment, their methods, and their procedures in view of the characterization measurements. In each of these cases, a considerable extra number of samples is needed. 

The third approach is also known as a collaborative study or a collaborative trial. Both names underpin the joint effort of the coordinator and participants to characterize the reference material. In any case, the measurement methods used in the characterization should be traceable to what is called stated references , and preferably to SI. The aspect of traceability of measurement results goes well beyond the actual measurements it also includes the transformation of the sample from the state of the reference material to the state in which it can be measured. An example of such a transformation is the destruction of the sample. 

Ward GM and Heeney HB (1960) A collaborative study of methods for the determination of potassium, calcium and magnesium in plant materials. Canad J Plant Sci 40 589-595. 

Bogershausen W, Cicciarelli R, Gercken B, Konig E, Krivan V, Muller-Kaeer R, Pavel J. Seltner H, Schelcher J 1997) Pure graphite as a reference material for the determination of trace elements - an interlaboratory collaborative study. Fresenius J Anal Chem 357 266-273. 

Kramer KJM, Dorten WS, Groenewoud H van hex, de Haan E, Kramer GN, Monteiro L, Muntau H, Quevauviller Ph (1999) Collaborative study to improve the quality control of rare earth element determinations in environmental matrices. J Environ Monit 1 83-89. 

After the performance of collaborative studies organized by the RIVM (National Institute of Ihiblic Health and Environmental Protection, Bilthoven, The Netherlands) and SM T certification studies were performed by a group of eleven or twelve qualified European laboratories. These examined simultaneously the materials using standardized methods following a very strict analytical protocol. Table 5.1 below shows data for CRM 506 (Mooijman et al. 1999)-... 

In such a case, based on the results of a collaborative study, a content is assigned to the corresponding reference substance which is method specific, i.e. it is only to be used with the method described in the monograph. The establishment of these substances is described in more detail later in the Chapter. 

Exchanges between pharmacopoeias are co-ordinated by the Pharmacopoeial Discussion Group (PDG) (International Harmonisation 1995) and it is frequent that one pharmacopoeia participates in a collaborative study organized by another pharmacopoeia, or that several pharmacopoeias share the same batch of reference substance to be used in their respective monographs nevertheless, in this case the reference substance can not be considered as harmonized. A new batch of erythromycin was shared between the United States Pharmacopoeia and the European Pharmacopoeia and was established in a common coEaborative study both for the microbiological assay (used in the USP for formulations) and the liquid chromatographic assay (used in the Ph. Eur. and USP for bulk material). 

Poole S, Dawson P and Gaines RE (1997) Second international standard for endotoxin calibration in an international collaborative study. J. Endotoxin Res. 4 221-231. 

Drawing on this representation, an approach has been described to systematically describe selection of food products to evaluate the applicability of collaboratively studied methods over a range of food matrices (Wolf and Andrews 1995). A food matrix is described by its location in one of the nine sectors in the triangle. Foods falling within the same sector are chemically similar and thus should behave in a similar analytical manner. This same scheme can be used to select food matrices representing each sector for development of a series of RMs representing all foods. 

Fig. 6.1 Schematic layout of food matrices suggested for a collaborative study based on protein (Prot), fat and carbohydrate (Cho) content, excluding moisture and ash...

We performed collaborative studies using the ELISA methods with model processed foods (sausage, boiled beef in an aluminum pouch, tomato sauce, biscuit, juice, and jam) containing allergen proteins. The six... 

Calibration data (e.g., linearity or sensitivity) are not discussed in detail between laboratories, but a typical calibration starts with 50% of the lowest fortification level and requires at least three additional calibration levels. Another point of calibration is the use of appropriate standards. In 1999 a collaborative study tested the effect of matrix residues in final extracts on the GC response of several pesticides.Five sample extracts (prepared for all participants in one laboratory using the German multi-residue procedure) and pure ethyl acetate were fortified with several pesticides. The GC response of all pesticides in all extracts was determined and compared with the response in the pure solvent. In total, 20 laboratories using 47 GC instruments... 

Chymostatin-sensitive Il-generating enzyme Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction Trial Collaborative Study Captopril Trial ( The Effect of Angiotensin-Converting Enzyme Inhibition on Diabetic Nephropathy ) calcium channel blocking agents Candesartan in Heart Failure Assessment of Reduction in Morbidity and Mortality Trial congestive heart failure, but the latest recommendations use HF for heart failure chronic kidney disease cardiac output... 

It should be mentioned that the Food Additives Analytical Manual (FAAM) [75] provides analysts with FDA evaluated methodology (partly subjected to collaborative study) needed to determine compliance with food additive regulations, including procedures for indirect food additives, such as butylated hydroxy-anisole (BHA), butylated hydroxytoluene (BHT), t-butylhydroxyquinone (TBHQ), dilaurylthiopropionate (DLTDP), fatty acid methyl esters (FAME), sodium benzoate, sorbitol, and others. 

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