Strategies for internal quality control in antidoping analyses

Internal quality control (IQC) is one of the most important elements contributing to quality assurance in the laboratory. In this study, the strategy for the implementation of an IQC program to monitor performance of the analytical procedures used in an antidoping control laboratory is presented. Different IQC parameters have been defined according to the aim of the method (qualitative or quantitative, screening or confirmation). They are based on the analysis of control and calibration samples in each analytical batch and on the use of an internal standard in chromatographic methods. IQC parameters for chromatographic and immunological methods and the acceptance criteria used to check the quality control data obtained are described and discussed. These IQC procedures have been applied during routine antidoping analyses of more than 5000 samples per year in a laboratory accredited by the International Olympic Committee (IOC) and meeting the requirements of the quality standard ISO 17025.     

The rational use of proficiency tests and intercomparisons

 Interlaboratory comparisons (in the following abbreviated as intercomparisons) regarding tests, analyses or measurements are among the most worthwhile measures a laboratory can take in order to confirm that its services to clients include the provision of correct results within a stated uncertainty. They give a picture of the whole performance of the laboratory, and they should be used much more than at present. Unfortunately such intercomparisons are, and are made, expensive and prestigious by the formalisms employed in many cases. The connection between intercomparisons and proficiency tests and their use for different purposes is briefly discussed. Some suggestions are made on how to improve the present state of the art, i.e. how to increase the use of intercomparisons, how to perform them efficiently and how to make optimal use of the results. Received: 6 December 1997 · Accepted: 30 January 1998     

Performance testing activities for analytical assessment of supercritical fluid extractors

Systematic performance testing activities for supercritical fluid extractors consistent with the implementation of quality systems in analytical laboratories are proposed. In this context, supercritical fluid extraction (SFE) is used for the automatic processing of complex samples. Ensuring reproducible operation of SFE equipment is crucial with a view to obtaining traceable results. To this end, an assessment protocol including recommended preventive and corrective actions, and complementary internal quality control activities, was developed with a view to facilitating the use of SFE equipment by routine analytical laboratories.     

Plans for implementation of a quality system in the control laboratory of the Romanian National Medicines Agency

This paper describes the practical implementation of a quality system in the control laboratory of the National Medicines Agency, Romania, the main aim being the alignment of the requirements of the control of drugs in Romania with European Union standards. Activity in this field is relatively new in Romania, however, it is of great importance to Romania’s compliance with international standards. Received: 13 September 2000 Accepted: 19 February 2001     

Proficiency testing on the analytical control of precious metal production

Our experience of executing proficiency testing programs on the analysis of precious metals and precious metal bearing materials is summarized. Six proficiency testing programs of the ”distributed sample testing” type were carried out using samples essentially distinct from each other: (I) certified samples of fine gold and fine silver, and (II) recoverable raw (scrap and catalyst waste) containing precious metals of unknown contents. The test results were assessed using the London Bullion Market Association (LBMA) rules and by Z-criteria using the ISO/IEC Guide 43 scale. Satisfactory results were presented by all participants for the analysis of certified samples of fine gold and fine silver. The results of catalyst waste analysis agreed rather well, whereas the scrap analysis revealed an essential discrepancy in the data for some samples. The reasons for such discrepancies are discussed. Received: 9 June 2000 Accepted: 21 November 2000     

A model to set measurement quality objectives and to establish measurement uncertainty expectations in analytical chemistry laboratories using ASTM proficiency test data

A model is presented that correlates historical proficiency test data as the log of interlaboratory standard deviations versus the log of analyte concentrations, independent of analyte (measurand) or matrix. Analytical chemistry laboratories can use this model to set their internal measurement quality objectives and to apply the uncertainty budget process to assign the maximum allowable variation in each major step in their bias-free measurement systems. Laboratories that are compliant with this model are able to pass future proficiency tests and demonstrate competence to laboratory clients and ISO 17025 accreditation bodies. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/ 10.1007/s007690100398-y. Received: 31 March 2001 Accepted: 11 September 2001     

Analytical quality control for the determination of polychlorobiphenyls in environmental matrices

Analytical quality control procedures for ensuring reliable data in the determination of PCBs in environmental matrices are described. Several extraction procedures of PCBs from sediment samples are critically compared and recovery and reproducibility for PCBs determination in sediment and cod liver oil samples are evaluated. Extraction by 1:1n-hexane/acetone mixture in an ultrasonic bath and by supercritical fluids generally give a quantitative recovery and a coefficient of variation lower than 15%, while extraction by a Soxhlet system does not give such good results and requires much longer extraction times. Certified reference materials available from three international organizations, namely the Standards, Measurements and Testing programme of the European Union, the USA National Institute of Standards and Technology and the National Research Council of Canada were used. Finally, the on-going European Union QUASIMEME programme aimed at improving the analytical quality of marine pollution monitoring measurements of European laboratories is addressed.     

A framework for the application and materials in analytical chemistry

 Working group 5 of EuraChem Nederland has developed a framework for the implementation of reference materials in analytical chemistry. In this discussed paper, the framework is proposed as a tool for the development of standard operation procedures (SOPs) in laboratories. The implementation of (certified) reference materials in these SOPs is of major importance in establishing comparability and traceability in measurement results, which in turn play a crucial role in measurement in support of trade, environmental issues, and characterisation of materials. Recent developments in the field of uncertainty analysis require the application of reference materials. It is recognised that the calculation of the combined measurement uncertainty becomes almost impossible without the use of certified reference materials with a stated uncertainty. Received: 1 December 1995 Accepted: 20 December 1995     

A validation concept for purity determination and assay in the pharmaceutical industry using measurement uncertainty and statistical process control

 The analytical chemists in process development in the pharmaceutical industry have to solve the difficult problem of producing high quality methods for purity determination and assay within a short time without a clear definition of the substance to be analyzed. Therefore the quality management is very difficult. The ideal situation would be that every method is validated before use. This is not possible because this would delay the development process. A process-type quality development approach with an estimation type fast validation (measurement uncertainty) is therefore suggested. The quality management process consists of the estimation of measurement uncertainty for early project status. Statistical process control (SPC) is started directly after measurement uncertainty estimation and a classical validation for the end of the project. By this approach a process is defined that allows a fast and cost-efficient way of supporting the development process with the appropriate quality at the end of the process and provides the transparency needed in the development process. The procedure presented tries to solve the problem of the parallelism between the two development processes (chemical and analytical development) by speeding up the analytical development process initially. Received: 25 March 1997 · Accepted: 17 May 1997     

Basic skills of analytical chemistry: do we take too much for granted?

 This paper examines some questions which arose from the competition organised by the Laboratory of the Government Chemist in conjunction with the Nuffield Curriculum Projects Centre and from years of experience in higher education. It goes on to indicate the ways that some of these problems may be tackled.     

Validation criteria for developing ion-selective membrane electrodes for analysis of pharmaceuticals

 The problem of validation criteria for developing ion-selective membrane electrodes for the analysis of pharmaceuticals arises from the connection between the reliability of ion-selective membrane electrodes construction and the reliability of the analytical information. Liquid membrane selective electrodes are more suitable for validation than the solid variety. The influence of the stability of ion pair complexes from the membrane on various parameters (e.g. response, limit of detection, and selectivity) is discussed. Validation criteria are proposed. Received: 18 September 1997 · Accepted: 17 November 1997     

Quality assurance in clinical chemistry laboratories in the UK

 Since the mid-1960s quality assurance in clinical chemistry has progressed from a need to define and improve precision and accuracy in analytical test procedures to an all-embracing process of assuring that the whole process of pre-analytical, analytical and post-analytical phases of handling patient samples is managed effectively and efficiently. Automated and computer-controlled equipment has reduced many of the analytical errors, in particular in imprecision, that were present in manual analysis. New management techniques have been developed to control the quality and appropriateness of results. Developments in internal quality control and external quality assessment procedures have enabled laboratories to continually improve the quality of assays. Laboratory accreditation and external quality assessment scheme accreditation have ensured that peer review and peer pressure have been applied to both laboratory and external quality assessment scheme performance. As the NHS reviews its priorities and places more emphasis on primary care provider demands, hospital laboratories will of necessity assist with near patient testing outside the laboratory. This will provide new challenges to the quality of the service provided. Received: 2 July 1998 · Accepted: 1 August 1998     

Statistical quality control of PCDD/PCDF analysis using a total measuring data set

 A random error and accuracy estimation approach for polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) analysis is presented based on statistical treatment of all the data set registered in a run or in a bunch of uniform runs. Received: 18 August 1998 / Accepted: 21 October 1998     

Performance of recently developed kinetic energy density functionals for the calculation of hydrogen binding strengths and hydrogen-bonded structures

 The accuracy of predicted hydrogen binding energies and equilibrium structures for a benchmark set of molecules is compared for some recently developed density functionals, Becke's three parameter hybrid method with the Lee, Yang, and Parr (LYP) correlation functional (B3LYP), Becke's half and half functional combined with the LYP correlation functional (BHLYP), Perdew, Burke and Ernzerhof functional (PBE), Van Voorhis, Scuseria exchange correlation functional (VSXC), the hybrid Perdew, Burke and Ernzerhof functional (PBE1PBE), and meta-generalized gradient approximation (meta-GGA). Overall, the hybrid functionals which contain a portion of Hartree–Fock exchange (B3LYP, BHLYP, and PBE1PBE) yield the most accurate results. The kinetic-energy-density-dependent functionals, VSXC and meta-GGA, are significantly less accurate. Received: 10 December 1999 / Accepted: 5 March 2000 / Published online: 21 June 2000     

Sampling and analytical framework for routine environmental monitoring of organic pollutants

Dubious data would lead to incorrect interpretations and consequently faulty conclusions. Environmental monitoring results therefore have to be unambiguous to avoid misunderstanding the problems under investigation. Representative sampling and appropriate laboratory procedures are keys to acquiring quality data in order to draw unbiased conclusions.Although a large number of studies on organic pollutants have been published, few efforts have been directed towards instituting a systematic framework from sampling design to instrumental analysis. Generally, the main components in such a framework should include sampling design, sample preparation, sample extraction, extract purification and fractionation, and quantification (including qualitative and quantitative analyses).This review outlines the sampling and analytical framework appropriate for routine monitoring of organic pollutants, particularly persistent organic pollutants widely occurring in the environment. We emphasize statistically-based sampling schemes and quality-assurance and quality-control measures desirable for environmental monitoring programs.By way of demonstrating their importance, we especially review procedures for collecting unconventional environmental samples (e.g., human blood, breast milk, human hair, fish and bird tissues, and ice and snow) and analytical methods for typical emerging organic chemicals.     

The generalized hybrid orbital method for combined quantum mechanical/molecular mechanical calculations: formulation and tests of the analytical derivatives

 Hybrid quantum mechanical (QM) and molecular mechanical (MM) potentials are becoming increasingly important for studying condensed-phase systems but one of the outstanding problems in the field has been how to treat covalent bonds between atoms of the QM and MM regions. Recently, we presented a generalized hybrid orbital (GHO) method that was designed to tackle this problem for hybrid potentials using semiempirical QM methods [Gao et al. (1998) J Phys Chem A 102: 4714–4721]. We tested the method on some small molecules and showed that it performed well when compared to the purely QM or MM potentials. In this article, we describe the formalism for the determination of the GHO energy derivatives and then present the results of more tests aimed at validating the model. These tests, involving the calculation of the proton affinities of some model compounds and a molecular dynamics simulation of a protein, indicate that the GHO method will prove useful for the application of hybrid potentials to solution-phase macromolecular systems. Received: 4 October 1999 / Accepted: 18 December 1999 / Published online: 5 June 2000     

It is never too early to introduce measurement and quality concepts: a proficiency test competition for schools and colleges

 This paper describes how the LGC and the Nuffield Curriculum Projects Centre set up an analysis competition for 16- to 19-year-old students. The competition was based on the procedure for proficiency testing. The results and reports give some insight into current standards of teaching and learning about analytical procedures and the treatment of uncertainty in courses at this level. The outcomes justify the production of a good-practice guide for teachers so that they can introduce concepts of valid analytical measurement into pre-university courses.     

Reference materials and analytical standards to stimulate improved laboratory performance: Experience from the external quality assessment scheme for trace elements in biological samples

The performance of a large number of laboratories measuring trace elements in biological fluids has been monitored over many years by examination of their results in the Guildford external quality assessment scheme. Specific experiences of the UK trace elements reference laboratories have been used to stimulate improvements in performance of other participants in the scheme. The key features of these initiatives were: specially prepared reference materials, used as internal quality control specimens within a common procedure, contributed to accuracy control; proposed standards of satisfactory and unacceptable analytical performance associated with a new system for scoring; regular non-threatening open discussion of performance with interested colleagues. The impact of these features is illustrated with reference to measurements of Al and Zn in serum and Pb in whole blood.