Quality control valid analytical measurements

Certified reference materials are used to provide reference values to facilitate the development and validation of analytical methods, and for the calibration, verification, and quality control of analytical measurement systems. 

Quality Assurance/Quality Control. QA/QC measures included field blanks, solvent blanks, method blanks, matrix spikes, and surrogates. Percent recovery was determined using three surrogate compounds (nitrobenzene-d5, 2-fluorobiphenyl, d-terphenyl-diQ and matrix spikes (naphthalene, pyrene, benzo[ghi]perylene) the recoveries ranged from 80 to 102%. Separate calibration models were built for each of the 16 PAHs using internal standards (naphthalene-dg, phenanthrene-dio, perylene-di2). Validation was performed using a contaminated river sediment (SRM 1944) obtained from NIST (Gaithersburg, MD) accuracy was <20% for each of the 16 analytes. 

In recent years the term qualimetrics has been coined to refer to the use of chemometrics for the purposes of quality control (Massart et al. 1997). ft relates particularly to the use of multivariate analysis of process control measurements. Other texts on quality assurance in chemical laboratories include the latest edition of Garfield s book published by AOAC International (Garfield et al. 2000), material published through the Valid Analytical Measurement program by the LGC (Prichard 1995), and books from the Royal Society of Chemistry (Parkany 1993,1995 Sargent and MacKay 1995). Wenclawiak et al. (2004) have edited a series of Microsoft PowerPoint presentations on aspects of quality assurance. 

CRMs are an important tool for quality assurance and quality control in analytical laboratories. They are used for verification of accuracy and precision (i.e., reliability of the results of analysis, validation of analytical procedures, establishing measurement traceability, and calibration of measurement equipment). Use of CRMs is recommended by the ISO/IEC 17025 standard and therefore it is obligatory for those who wish to obtain and maintain accreditation of the laboratory. 

In many cases and circumstances of the daily quality control of analytical work RMs and CRMs are helpful tools. Very often RMs are sufficient, in particular for statistical control actions. Where a rough estimate of accuracy or even precision is sufficient, a simple RM or calibration material is also largely adequate. However, for the establishment of the accuracy in the procedure of method development and validation, for revalidation of modified methods or whenever the analyst needs to demonstrate accuracy, e.g. measurements for court cases, CRMs should be employed as they have the advantage of being certified. It will be up to the operator and the laboratory s quality management to determine when, where, and how RM or preferably CRMs shall be used. 

Certified reference materials are intended primarily for calibration and in quality control of analytical techniques. A certified reference material is a reference material, accompanied by a certificate, one or more of whose property values are certified by a procedure that establishes its traceability to an accurate realization of the unit in which the property values are expressed and for which each certified value is accompanied by an uncertainty at a stated level of confidence. They are used to test, validate, and optimize new analytical techniques as well as in quality control of routine laboratory work. Table 3 gives a list of environmental samples that provide certified values of PAH content. These are available from various bodies as certified reference materials. In measuring the concentration of a substance for certification purposes, more than two independent and reliable analytical methods are used. Certified reference materials when used for standardization of analytical methods will make comparisons between PAH data obtained by a variety of workers using... 

Particularly for direct microanalytical techniques using <10 mg of sample for analysis, it is highly desirable to obtain quantitative information on element- and compound-specific homogeneity in the certificates for validation and quality control of measurements. As the mean concentration in a CRM is clearly material-related, the standard deviation of this mean value should represent the element s distribution in this matrix rather than differences in the analytical procedures used. 

Untreated (control) soil is collected to determine the presence of substances that may interfere with the measurement of target analytes. Control soil is also necessary for analytical recovery determinations made using laboratory-fortified samples. Thus, basic field study design divides the test area into one or more treated plots and an untreated control plot. Unlike the treated plots, the untreated control is typically not replicated but must be sufficiently large to provide soil for characterization, analytical method validation, and quality control. To prevent spray drift on to the control area and other potential forms of contamination, the control area is positioned > 15 m away and upwind of the treated plot, relative to prevailing wind patterns. 

With respect to method application, once validation has been satisfactorily completed, there is little question that use of the analytical method in worker safety and re-entry studies falls under the full requirements of the GLP Standards. In addition, there should be an adequate level of quality control measurements taken in conjunction with the specimens so as to provide for a meaningful assessment of accuracy and precision, as well as verification of freedom from artifactual interferences. Along with these measurements there needs to be reasonably rigid data acceptance criteria in place (usually established during validation) which are consistently applied during the course of the specimen analytical phase of the study. 

This chapter deals with handling the data generated by analytical methods. The first section describes the key statistical parameters used to summarize and describe data sets. These parameters are important, as they are essential for many of the quality assurance activities described in this book. It is impossible to carry out effective method validation, evaluate measurement uncertainty, construct and interpret control charts or evaluate the data from proficiency testing schemes without some knowledge of basic statistics. This chapter also describes the use of control charts in monitoring the performance of measurements over a period of time. Finally, the concept of measurement uncertainty is introduced. The importance of evaluating uncertainty is explained and a systematic approach to evaluating uncertainty is described. 

Baseline separation of the cephalosporin antibiotic cephradine, its main impurity cephalexin, and other related impurities was achieved by MEKC. The method was validated in compliance with the USP XXII analytical performance parameters and the results were comparable with a validated LC method, depicting CE to be a valuable alternative technique to LC in pharmaceutical quality control. In most cases, the amount of impurities relative to the main compound measured by MEKC is similar to that obtained by LC. However, some reports reveal that there are differences in number and amount of impurities between MEKC and LC analysis. MEKC permitted the determination of seven known and three unknown impurities in cefotaxime and the results were in good agreement with those of LC. ° MEKC yielded a higher amount of the cefotaxime dimer but a lower amount of an unidentified impurity with respect to LC. The differences may be due to the easier formation of the dimer in the aqueous sample solvent used in MEKC compared to the hydroorganic... 

Not all methods require each parameter detailed in table 8.2 to be established. For example, a method that only measures the active ingredient in a 100-mg cold cure as part of a quality control protocol is not concerned with limit of detection, the matrix is fixed, and the calibration range might only need to be established between 80 and 120 mg. An analysis that determines the presence or absence of the target analyte needs only to establish its selectivity, limit of detection, and ruggedness. Table 8.3 details some common analytical systems with their critical method validation parameters. 

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. 

Hansen, V., Clausen, P.A. and Wolkoff, P. (2001) Quality control measures for FLEC emission testing-validation af analytical method. Proceedings of Second International FLEC Symposium, pp. 116-20. 

When the analytical laboratory is not responsible for sampling, the quality management system often does not even take these weak links in the analytical process into account. Furthermore, if sample preparation (extraction, cleanup, etc.) has not been carried out carefully, even the most advanced, quality-controlled analytical instruments and sophisticated computer techniques cannot prevent the results of the analysis from being called into question. Finally, unless the interpretation and evaluation of results are underpinned by solid statistical data, the significance of these results is unclear, which in turn greatly undermines their merit. We therefore believe that quality control and quality assurance should involve all the steps of chemical analysis as an integral process, of which the validation of the analytical methods is merely one step, albeit an important one. In laboratory practice, quality criteria should address the rationality of the sampling plan, validation of methods, instruments and laboratory procedures, the reliability of identifications, the accuracy and precision of measured concentrations, and the comparability of laboratory results with relevant information produced earlier or elsewhere. 

Once the analytical parameters have been determined from the method development and the method has proven suitable for routine measurements, internal quality control (IQC) procedures must be established to maintain the validity of the analytical scheme and to better monitor potential sources of errors. The IQC used includes pre- and post-digestion controls, blank determination, half range of the calibration graph checking, and recovery rate of the samples. The stability of the recovery rate with time (Fig. 1.4) shows that the method is robust after using... 

Generally, the analysis of environmental pollutants is considered as a necessary expense that is performed solely if stated by law. With less expensive screening methods and automated modern equipment to analyze suspect samples, the cost of analysis will become much lower. Hence, the attitude towards QA would most probably be more positive and the analytical work much more reliable for the customers. This also strengthens the international competitiveness of European producers. The credibility of the entire monitoring chain (screening methods, reference and standardized methods, as well as CRMs for the quality control of these methods) lies in the adequacy and integration of all three levels of the system. The adequate development and validation of methods is a prerequisite for a harmonized measurement system [80]. 

Quite obviously, the quality of analytical results strongly depends on the representativeness of the sample examined, the appropriateness of the pretreatment procedures applied for the quantitative conversion of analytes into detectable forms, and the btness for purpose of the laboratory setting. Because of the low concentration and the numerous interferences which affect the various detection systems, measurements methods must be thoroughly validated. Even if values obtained by several laboratories for PGEs concentrations in environmental and biological samples were compliant with the basic requirements of quality assurance (QA) and internal quality control (QC), striking differences have been... 

The frequency of the control sample analysis depends on the nature of the analysis. Successful analysis of the control samples assures that the system is performing as expected under the SOP. Validation of HPLC equipment assures that valid measurements are obtained. The quality of the analytical data can be maintained by keeping, in a safe place, records of the actual instrument conditions at the time the measurements were made. Backups should also be maintained. 

---