Additional Method Performance Evaluations

Some biomarker methods may require the evaluation of additional performance measures. The performance measures are generally conducted on a case-by-case basis and are evaluated based on laboratory experience with the tech-nology/platform or with the species and sample type being studied. Some common performance measurements include but are not limited to  

Ellington A, Kullo IJ, Bailey KR, Klee G. Antibody-Based Protein Multiplex Platforms Teehnieal and Operational Challenges. Clinical Chemistry 2010 56(2), 186-193. 

European Medicines Agency (EMA). Guidance for Industry Bioanalytical Method Validation. EMEA, London, UK 2011. 

Findlay JWA, et al. Validation of Immunoassays for Bioanalysis A Pharmaceutical Industry Perspective. Journal of Pharmaceutical and Biomedical Analysis 2000 21,1249-1273. 

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The fundamental chemistry, especially of the newer economic poisons, is of primary importance. The mechanism of action of the various types of economic poisons and the relation of structure to toxicity of insects are of fundamental interest. Chemical versus biological methods of evaluation should be presented. Performance methods of evaluation of these chemicals have been given careful consideration by several workers. Emphasis was placed by several workers on the need for much additional information on various aspects of the problem regarding the use of DDT, 2,4-D, and other pesticides. There is direct importance in studies on the metabolism of DDT. 

The previous chapters of this book have discussed the many activities which laboratories undertake to help ensure the quality of the analytical results that are produced. There are many aspects of quality assurance and quality control that analysts carry out on a day-to-day basis to help them produce reliable results. Control charts are used to monitor method performance and identify when problems have arisen, and Certified Reference Materials are used to evaluate any bias in the results produced. These activities are sometimes referred to as internal quality control (IQC). In addition to all of these activities, it is extremely useful for laboratories to obtain an independent check of their performance and to be able to compare their performance with that of other laboratories carrying out similar types of analyses. This is achieved by taking part in interlaboratory studies. There are two main types of interlaboratory studies, namely proficiency testing (PT) schemes and collaborative studies (also known as collaborative trials). 

Several method performance indicators are tracked, monitored, and recorded, including the date of analysis, identification of equipment, identification of the analyst, number and type of samples analyzed, the system precision, the critical resolution or tailing factor, the recovery at the reporting threshold level, the recovery of a second reference weighing, the recovery for the control references (repeated reference injections for evaluation of system drift), the separation quality, blank issues, out of spec issues, carry over issues, and other nonconformances. The quantitative indicators are additionally visualized by plotting on control charts (Figure 23). 

While the provision of suitably validated analytical methods is a necessary requirement for ensuring compliance with MRLs, the method alone is not sufficient to ensure creditable analytical measurements. In addition to selecting suitable methods, the analyst must demonstrate that the method is operating under statistical control in the laboratory and is performed to meet performance specifications as required by the analytical problem. This means that all methods should be applied in an environment with appropriate quality assurance procedures and performance evaluation checks. 

The unsaturated zone, where most of the low-level waste is buried, could probably be used for high-level waste after cooling but it does not lend itself to the regional approach to defining permeability. Additionally, the laboratory methods of evaluating permeability of unsaturated material are extremely difficult to perform consistently. However, an air permeability technique that may prove useful in evaluating the zone between the surface and the water table was developed by Weeks W. The technique uses normal barometric fluctuations measured at different depths in the formation to determine permeability to air which can be used to determine permeability to water. 

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. 

In principle, methods should be validated for each type of matrix and for the extraction agent applied. Matrix effects may affect strongly the calibration (e.g. loss of signal, interferences). Standard addition techniques are, therefore, the only way to control the validity of the detection, but only if the addition is performed with the proper identical form of the compound to be determined. As stressed above, it is of primary importance to evaluate this linear range before starting the analysis so that the spiked levels remain in the linear range of the detector response (Quevauviller et al., 1996a). 

Lopez-Avila et al. [8] published a study in 1993 that evaluated the Soxtec extraction of 29 target compounds (seven nitroaromatic compounds, three haloethers, seven chlorinated hydrocarbons, and 12 organochlorine pesticides) from spiked sandy clay loam and clay loam. Among the five factors investigated (matrix type, spike level, anhydrous sodium sulfate addition, total extraction time, and immersion/extraction time ratio), matrix type, spike level, and total extraction time had the most pronounced effects on method performance at the 5% significance level for 16 of the 29 target compounds. The two solvent mixtures, hexane-acetone (1 1) and methylene chloride-acetone (1 1), performed equally well. Four compounds were not recovered at all, and apparently were lost from the spike matrix. Limited experimental work was performed with 64 base-neutral-acidic compounds spiked onto clay loam, and with three standard reference materials certified... 

Since the small volume vessels and minipaddles were noncompendial, additional studies were performed to confirm the appropriateness of the method parameters selected and the discriminatory ability of the method. The effect of paddle speed, paddle height and sampling zone were evaluated in an experimental design of experiment study. In addition, the discriminatory ability of the method was evaluated using purposefully perturbed or aberrant tablets, to model poorly dissolving tablets. 

In addition, a great need exists for improved test procedures to predict end-use performance. The correlations between accelerated exposure devices and normal fluorescent lamps, described in this report, represent only a preliminary effort to refine and establish meaningful laboratory methods for evaluating light stabilizers. Exposure data from a greater number of samples, containing a greater variety of formulations, are needed for more accurate correlations. 

The ultimate measurement of trap performance is if microactivity increases at constant fresh catalyst additions and metals levels or if the improved stability provides the flexibility to reduce additions or process higher vanadium containing feed. From an evaluation standpoint, it helps to have additional methods of determining success. 

The variation of sensitivity between different sensors was also checked. Calibration curves with five different sensors were performed. A Relative Standard Deviation of 13, 13 and 42% of calibration slopes (sensitivity) were obtained for Cu, Pb and Cd respectively. These variations should have limited consequence on bias and precision when the standard addition method is used. However, for Cd, variations in the limit of quantification between two electrodes could be expected. Finally, the accuracy of the method was evaluated by the measurement of a SWIFT reference material used during the 2nd SWIFT-WFD Proficiency Testing exercise (Table 4.2.2). The reference value was chosen as the consensus value of the selected data population obtained after excluding the outliers. The performances of the device were estimated according to the Z-score (Z) calculation. Based on this score, results obtained with the SPEs/PalmSens method were consistent with those obtained by all methods for Pb and Cu ( Z < 2) while the result was less satisfactory for Cd (2 < Z < 3). 

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]. 

Additional performance evaluations are also conducted in commercial washing machines. Although this method does not permit testing in as controlled a fashion as the launderometers, they do predict consumer-relevant behavior. Soiled fabric... 

Several measurements can be performed on the same sample for e.g., wide-range spectrophotometry, simultaneous determinations, selectivity evaluation, accuracy assessment or compensation of matrix effects by the standard addition method. Each measurement normally relates to a different sample (or standard) volumetric fraction, hence a different degree of dilution. To this end, different approaches involving single or multiple sample (or standard) insertions and/or exploitation of concentration gradients have been used, as emphasised in Chapter 7. 

In addition, tabulated data from calibration curves, precision and accuracy data sets, selectivity experiments (spiking of matrices from individual sources), and baseline evaluations (for cut point analysis) will provide valuable information on method performance and should be compared with similar data sets from the sending lab. 

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