Validation requirements for chemical methods in quantitative analysis – horses for courses?

 Although the validation process necessary to ensure that an analytical method is fit for purpose is universal, the emphasis placed on different aspects of that process will vary according to the end use for which the analytical procedure is designed. It therefore becomes difficult to produce a standard method validation protocol which will be totally applicable to all analytical methods. It is probable that far more than 30% of the methods in routine laboratory use have not been validated to an appropriate level to suit the problem at hand. This situation needs to change and a practical assessment of the degree to which a method requires to be validated is the first step to a reliable and cost effective analytical industry. Received: 22 September 1997 · Accepted: 28 November 1997     

Clinical reference materials for the validation of the performance of photometric systems used for clinical analyses

 There are a wide variety of spectrophotometric devices nowadays used in health services with various qualities of manufacture methods of measurement and metrological characteristics for performing the necessary measurements. Therefore, to meet the accuracy and repeatability requirements needed in medical diagnosis and treatment, the validation of the performance of such systems by clinical chemistry laboratories is essential. However, the validation of a spectrophotometric system for clinical analyses requires several reference materials, according to the end use of the measurement results. This paper discusses some characteristics required of the clinical reference materials needed and used by Romanian Institute of Metrology for validation work. Types of clinical reference materials developed in the national area for this purpose are also presented. Received: 23 April 1997 · Accepted: 7 July 1997     

Flexibilization of the scope of accreditation: an important asset for food and water microbiology laboratories

Beltest, the Belgian accreditation body, has investigated flexibilization of the scope of accreditation for chemistry laboratories and food and water microbiology laboratories. This flexibilization, synonymous with test-type accreditation, allows a laboratory to add new test methods or retry previous test methods without having to undergo a new audit by Beltest. It has been used for nearly ten years by German and Swiss accreditation bodies. Flexibilization permits the validation of methods and results, given that the competence of the particular laboratory is already well established. This new concept in microbiology allows client’s needs to be adequately met, and facilitates the quick establishment of a method in several laboratories at once in case of a public health crisis. The first laboratory to participate at this investigation on the flexibilization concept, as a test of the concept, was the Belgian reference laboratory for food microbiology.     

Validation of an HPLC method for the determination of *-dichlorobenzene and naphthalene in mothrepellents

 The determination of dichlorobenzene and naphthalene in commercial repellents used in Spain has been validated. This was done using an isocratic regime, to test the reverse -phase HPLC system with acetonitrile: water 65 : 35 (v: v) as the mobile phase, at 20  °C. This technique is proposed for the modular validation of the HPLC system . The results obtained with this method show good agreement with the results provided by the manufacturers of the mothrepellents. Received: 21 December 1998 / Accepted: 4 May 1999     

A need for clearer terminology and guidance in the role of reference materials in method development and validation

 The fact that various definitions and terminology applied to measurements in analytical chemistry are not always consistent and straightforward, by not only answering the question ”what”, but also ”how”, leads to their various interpretations. This results in non-uniform implementation of very basic and essential metrological principles in chemistry. Such a diverse situation is not conducive to the endorsement of harmonised measurements all across the world, to serve as a tool for improving the quality of life in its broadest sense for all its citizens. The discussion in this paper is focused on problems associated with terminology and definitions of ’reference material’ and ’validation’. The role of reference materials in measurement processes for purposes other than calibration and validation principles in analytical chemistry are also discussed in this paper. Where possible, potential solutions are proposed, but more often, questions of essential importance are raised in order to initiate international discussion which will hopefully lead to equally understandable answers. Received: 2 November 2002 Accepted: 3 February 2003 Acknowledgements   The author is grateful to Aleš Fajgelj for his comprehensive comments on the topic described in this paper. Sincere thanks also to Philip Taylor, Ewa Bulska, Emilia Vassileva, Miloslav Suchanek and Margreet Lauwaars for their contribution during fruitful discussions on validation. Presented at the CERMM-3, Central European Reference Materials and Measurements Conference: The function of reference materials in the measurement process, May 30–June 1, 2002, Rogaška Slatina, Slovenia Correspondence to N. Majcen     

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     

Dressed coupled-electron-pair-approximation methods for periodic systems

 The techniques of matrix dressing for configuration-interaction (CI)-type or coupled-electron-pair-approximation (CEPA)-type correlation treatments are reviewed with respect to the application to periodic systems. All methods ranging from canonical second-order M?ller–Plesset perturbation theory over CI of single and double excitation, CEPA-0 or the averaged-coupled-pair-functional to self-consistent size-consistent CI can be formulated completely equivalently as an eigenvalue problem or as a solution to a system of linear equations. The size consistency of each method is obtained in a natural way, and invariance under orbital rotations is clearly assessible. A remark on the size consistency of the Davidson correction is presented. Additionally, the direct generation of localized Hartree–Fock orbitals as basic ingredients for the correlation calculations are addressed, as well as selected results on ring molecules, polymers, and 3D cubic beryllium as a model crystal. Received: 28 August 1999 / Accepted: 5 March 2000 / Published online: 21 June 2000     

Bioanalytical method validation and its implications for forensic and clinical toxicology – A review

The reliability of analytical data is very important to forensic and clinical toxicologists for the correct interpretation of toxicological findings. This makes (bio)analytical method validation an integral part of quality management and accreditation in analytical toxicology. Therefore, consensus should be reached in this field on the kind and extent of validation experiments as well as on acceptance criteria for validation parameters. In this review, the most important papers published on this topic since 1991 have been reviewed. Terminology, theoretical and practical aspects as well as implications for forensic and clinical toxicology of the following validation parameters are discussed: selectivity (specificity), calibration model (linearity), accuracy, precision, limits, stability, recovery and ruggedness (robustness). Received: 16 June 2002 Accepted: 12 July 2002 Part of this review was published in the communications of the International Association of Forensic Toxicologists (TIAFT; TIAFT Bulletin 32 (2002): 16–23) and of the Society for Forensic and Toxicologic Chemistry (GTFCH; Toxichem and Krimitech 68 (2001): 116-126). Correspondence to F. T. Peters     

Chromatographic separation techniques and data handling methods for herbal fingerprints: a review

As herbal medicines have an important position in health care systems worldwide, their current assessment and quality control are a major bottleneck. Over the past decade, major steps were taken not only to improve the quality of the herbal products but also to develop analytical methods ensuring their quality. Nowadays, chromatographic fingerprinting is the generally accepted technique for the assessment and quality control of herbal products. This paper briefly considers the evolution of the regulations and guidelines on the quality control of herbal medicines, and reviews the established analytical techniques for herbal fingerprinting with an emphasis on the most recent developments, such as miniaturized techniques, new stationary phases, analysis at high temperatures and multi-dimensional chromatography. Accessory to the new analytical techniques, the chemometric data handling techniques applied are discussed. Chemometrics provide scientists with useful tools in understanding the huge amounts of data generated by the analytical advances and prove to be valuable for quality control, classification and modelling of, and discrimination between herbal fingerprints.     

Problems of validation of computerised instruments for accredited chemical laboratories

 Some problems of validation of computerised instruments are reviewed briefly, taking essential standards and guides into account. The significant role of certified standard reference materials is underlined. An attitude of suppliers towards the validation of instruments is presented, and producers' responsibilities and obligations are discussed. The "black-box" concept is recommended as a preliminary step for the validation of computerised instruments. Two examples for gel permeation chromatography are given that illustrate a bad manufacturer's practice (BMP) and good manufacturer's practice (GMP). In the case of BMP, a need is expressed for a guide and for regulations that should be implemented into the quality assurance system. It has been proposed that the EURACHEM/VAM draft of guidance for qualification/validation of instruments should be amended by incorporating the "black-box" approach as a preliminary procedure for validation of computerised instruments, a retrospective validation procedure if the need for current validation was not foreseen or not specified, and a procedure (or selection rules) for qualification of the supplier. Moreover, the mechanisms of inspection to control the observance of the standardised rules and commonly recognised recommendations should also be considered by international quality organisations. Received: 19 November 1996 · Accepted: 20 March 1997     

Accreditation of types of tests

 DACH, the German accreditation body of chemistry, which was founded in 1992, has introduced a new model for the flexibilization of the scope of accreditation. This ensures that the accreditation of a laboratory also guarantees flexibility. Flexibilization of the scope of accreditation is of great importance, in particular if a great number of similar routine tests (standard methods) or non-routine tests are to be accredited. The main tool of flexibilization is the accreditation of types of tests. The accreditation of types of tests entitles laboratories to include additional test methods within the type of test accredited without informing the accreditation body immediately. Such information is provided at fixed surveillance intervals. The conditions for the accreditation of types of tests are described below.     

Limits of detection, identification and determination: a statistical approach for practitioners

 For the estimation of the limits of detection, identification and determination, considerations from analytical practice were applied to the statistics of the calibration line and its prediction interval. The detection limit was the concentration calculated from the maximum height of the prediction interval at zero spiking concentration. The identification limit was twice the detection limit and was the lowest concentration that could safely be detected. The determination limit was the lowest concentration fulfilling three criteria: 1. None of the signals resulting from determination limit concentration should interfere with any signal from detection limit concentration, thus providing an unambiguous separation between the two limits. 2. Recovery should be between 70% and 120%. 3. Lowest and highest predictable signal at determination limit concentration should not deviate more than ± 30% from the average. Practical analytical guidance and the necessary mathematical formulae are presented. Received: 12 November 1997 · Accepted: 7 December 1997     

Parameterization of semiempirical methods to treat nucleophilic attacks to biological phosphates: AM1/d parameters for phosphorus

 This paper reports a new AM1/d model for phosphorus that can be used to model nucleophilic attack of phosphates relevant for biological phosphate hydrolysis reactions. The parameters were derived from a quantum dataset calculated with hybrid density-functional theory [B3LYP/6-311++G(3df,2p)//B3LYP/6-31++G(d,p)] of phosphates and phosphoranes in various charge states, and on transitions states for nucleophilic attacks. A suite of non-linear optimization methods is outlined for semiempirical parameter development based on integrated evolutionary (genetic), Monte Carlo simulated annealing and direction set minimization algorithms. The performance of the new AM1/d model and the standard AM1 and MNDO/d models are compared with the density-functional results. The results demonstrate that the strategy of developing semiempirical parameters specific for biological reactions offers considerable promise for application to large-scale biological problems. Received: 15 January 2002 / Accepted: 6 September 2002 / Published online: 28 March 2003 Contribution to the Proceedings of the Symposium on Combined QM/MM Methods at the 222nd National Meeting of the American Chemical Society, 2001 Correspondence to: D.M. York e-mail: york@chem.umn.edu Acknowledgements. D.M.Y. is grateful for financial support provided by the National Institutes of Health (grant 1R01-GM62248-01A1) and the Donors of The Petroleum Research Fund, administered by the American Chemical Society, and the Minnesota Supercomputing Institute through a 6-month research scholar award (X.L.). Computational resources were provided by the Minnesota Supercomputing Institute.     

Primary reference materials and traceability chain for gas composition

This article briefly describes research on the development of primary reference gases and the traceability system of gas measurement at the National Research Center for Certified Reference Materials, China.     

Rapid determination of aristolochic acids I and II in herbal products and biological samples by ultra-high-pressure liquid chromatography-tandem mass spectrometry

Aristolochic acids (AAs) are a mixture of structural-related compounds, in which aristolochic acid I (AA I) and aristolochic acid II (AA II) are reported to be correlated with Aristolochic acid nephropathy (AAN). In this work, a rapid and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine AA I and AA II in herbal products and biological fluids. By using gradient elution with a mobile phase composed of a mixture of 10 mM ammonium formate buffer (pH 3.0) and acetonitrile, AAs could be determined within 10 min. Under optimum UHPLC-MS/MS conditions, the limit of detections was 0.14 and 0.26 ng mL⁻¹ for AA I and AA II, respectively. Run-to-run repeatability and intermediate precision of peak area for AA I and AA II were less than 5.74% relative standard deviation (RSD). Accuracy was tested by spiking 10, 100 and 1000 ng mL⁻¹ in rat serum and the recoveries were within 76.5-92.9%. Matrix effects were within 78.8-127.7%. The developed method was successfully applied to determine AA I and AA II in several herbal products and to investigate their pharmacokinetic behavior in female Wister rats. The result shows that the developed UHPLC-MS/MS method is efficient, sensitive, and accurate for the determination of AA I and AA II in herbal products and biological samples.     

Benefits arising from proficiency testing schemes: The comparison of analytical methods

 The primary objective of proficiency testing (PT) is in the provision of information and support to participating laboratories, to enable them to monitor and improve the quality of their measurements. However, other benefits can be obtained from PT. These include the comparison of data for a given measurement by different methods, the validation of new methods, and the provision of information for laboratories' customers and accreditation bodies. This paper considers the subject of method comparison, and highlights some of the approaches which can be followed, as well as the practical use to which this can be put, to benefit the analytical community more widely. This is illustrated by a case study concerning the measurement of haze in beer. In this study the United Kingdom Institute of Brewing (IoB) conducted a survey of participants in the Brewing Analytes Proficiency Scheme (BAPS). From the survey data taken together with data from the BAPS scheme, the IoB is now in a position to give guidance on the use of particular instruments and procedures, as well as consider changes to the scope of the BAPS scheme to provide greater benefits for participants concerned with measuring haze. Received: 3 March 1998 · Accepted: 9 June 1998     

Estimating measurement uncertainty: reconciliation using a cause and effect approach

 A strategy is presented for applying existing data and planning necessary additional experiments for uncertainty estimation. The strategy has two stages: identifying and structuring the input effects, followed by an explicit reconciliation stage to assess the degree to which information available meets the requirement and thus identify factors requiring further study. A graphical approach to identifying and structuring the input effects on a measurement result is presented. The methodology promotes consistent identification of important effects, and permits effective application of prior data with minimal risk of duplication or omission. The results of applying the methodology are discussed, with particular reference to the use of planned recovery and precision studies. Received: 28 October 1997 · Accepted: 17 November 1997