Quantitative validation of a flow-injection determination of penicillin in pharmaceutical formulations by means of a validation program based on an expert system

The quantitative validation of the results of a flow-injection determination of penicillin in pharmaceutical formulations is described. The validation procedure is done by using VALID, which is a generally applicable validation program based on an expert system program. The automated penicillin assay is based on the enzymatic hydrolysis of the penicillin to the corresponding penicilloic acid, which reacts with iodine generated on-line; the iodine consumption is detected amperometrically. The method is evaluated for applicability in pharmaceutical quality control. The complete validation procedure is described. During the program run, the system evaluates the calibration procedure, the drift of the analytical systemm and the effect of the sample matrix. The reliability of the flow-injection method is estimated by evaluating the maximum total error (MTE), which includes both random error and systematic error. The latter was assessed by comparing of the results of the flow-injection method with the results obtained by titration with mercury(II) as the reference method. The user requirement for the assay was an MTE of 10%. The validation procedure showed that the analytical method complied with the requirements for the major part of the concentration range (0.066–0.25 mM).     

Uncertainty in chemical analysis and validation of the analytical method: acid value determination in oils

Quantifying uncertainty in chemical analysis, according to EURACHEM document (1995), is based on known relationships between parameters of the analytical procedure and corresponding results of the analysis. This deterministic concept is different from the cybernetic approach to analytical method validation, where the whole analytical procedure is a "black box". In the latter case, analytical results only are the basis for statistical characterization of the method without any direct relationship with intermediate measurement results like weighings, volumes, instrument readings, or other parameters like molecular masses. This difference requires the harmonization of parameters to be validated and to be included in the uncertainty calculation. As an example, results of the uncertainty calculation and validation are discussed for a new method of acid value determination in oils by pH measurement without titration.     

Nuclear forensics—metrological basis for legal defensibility

The admissibility of nuclear forensics measurements and opinions derived from them in US Federal and State courts are based on criteria established by the US Supreme Court in the case of Daubert v. Merrell Dow and the 2000 Amendment of Rule 702 of the Federal Rules of Evidence. These criteria are being addressed by new efforts that include the development of certified reference materials (CRMs) to provide the basis for analytical method development, optimization, calibration, validation, quality control, testing, readiness, and declaration of measurement uncertainties. Quality data is crucial for all stages of the program, from R&D, and database development, to actual casework. Weakness at any point in the program can propagate to reduce the confidence of final conclusions. The new certified reference materials will provide the necessary means to demonstrate a high level of metrological rigor for nuclear forensics evidence and will form a foundation for legally defensible nuclear chemical analysis. The CRMs will allow scientists to devise validated analytical methods, which can be corroborated by independent analytical laboratories. CRMs are required for ISO accreditation of many different analytical techniques which may be employed in the analysis of interdicted nuclear materials.     

Evaluation of measurement uncertainties for the determination of total metal content in soils by atomic absorption spectrometry

In this work estimation of measurement uncertainties associated with the total metal content in soils was done by an intralaboratory approach based on method validation and quality control data, and using two certified reference materials (CRM). CRM and soil samples were analyzed following procedures based on the methods that are applied to silicate materials. All elements were determined by atomic absorption spectrometry following a quality assurance program previously established. Quality control actions were implemented in order to provide reliable data. The precision under within-laboratory reproducibility conditions was estimated from triplicate analysis. The trueness component was determined as recovery of the analyte from CRMs: soil sample, SO-2 and river clay sediment, LGC 6139. Combined measurement uncertainty was expressed in terms of precision and recovery uncertainties and the later further split on CRM replicate analysis and uncertainty of the certified value components. The results obtained are critically discussed on the basis of the different contributions. For the selection of the reference material, the CRM dependent terms are critically compared in order to fulfill specific requirements. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Use of an excess variance approach for the certification of reference materials by interlaboratory comparison

In the nuclear field, the accuracy and comparability of analytical results are crucial to insure correct accountancy, good process control and safe operational conditions. All of these require reliable measurements based on reference materials whose certified values must be obtained by robust metrological approaches according to the requirements of ISO guides 34 and 35. The data processing of the characterization step is one of the key steps of a reference material production process. Among several methods, the use of interlaboratory comparison results for reference material certification is very common. The DerSimonian and Laird excess variance approach, described and implemented in this paper, is a simple and efficient method for the data processing of interlaboratory comparison results for reference material certification. By taking into account not only the laboratory uncertainties but also the spread of the individual results into the calculation of the weighted mean, this approach minimizes the risk to get biased certified values in the case where one or several laboratories either underestimate their measurement uncertainties or do not identify all measurement biases. This statistical method has been applied to a new CETAMA plutonium reference material certified by interlaboratory comparison and has been compared to the classical weighted mean approach described in ISO Guide 35. This paper shows the benefits of using an “excess variance” approach for the certification of reference material by interlaboratory comparison.     

直读光谱法测定海洋结构用钢中的锆

采用直读光谱法,针对海洋结构用钢中的锆元素进行分析。实验利用标准物质,通过条件实验,建立海洋结构用钢中锆的工作曲线,确定海洋结构用钢中残余元素锆的分析方法。通过标准样品的结果验证以及待测试样的光谱分析方法与化学分析方法实验结果的比较,证明方法完全可以满足生产及新产品开发的要求,同时也拓宽了直读光谱仪的分析范围。     

Reference materials for small-sample analysis

Many modern analytical techniques use small solid samples and lack proper reference materials for their calibration and quality assurance. A remedy to this deficiency may be in the development of a new genre of highly homogeneous natural matrix materials, their properties being studied with analytical techniques such as PIXE and μ-PIXE, solid sampling AAS, scanning electron microscopy in combination with electron probe X-ray microanalysis, and INAA. Suitable natural materials may be obtained in form of single cell biological materials, finely dispersed suspensions and precipitates such as air particulate matter or sediments, and by appropriate particle size reduction of complex matrices. Initial studies have been carried out on single cell green algae biomass and air particulate matter, as well as several processed materials. Narrow particle size distributions with particles preferably below 10 μm diameter may assure the desired analytical homogeneity. The determination of sampling parameters for individual measurands will ascertain the utility of a material for small-sample analysis. Received: 16 June 1997 / Revised: 24 September 1997 / Accepted: 27 September 1997     

Evaluation of the analytical method performance for incurred samples

A methodology for the evaluation of the performance of an analytical method for incurred samples is presented. Since this methodology is based on intra-laboratory information, it is suitable for analytical fields that lack reference materials with incurred analytes and it can be used to evaluate the analytical steps prior to the analytical portion, which are usually excluded in proficiency tests or at the certification of reference materials. This methodology can be based on tests performed on routine samples allowing the collection of information on the more relevant combinations analyte/matrix; therefore, this approach is particularly useful for analytical fields that involve a high number of analyte/matrix combinations, which are difficult to cover even considering the frequent participation in expensive proficiency tests.This approach is based on the development of a model of the performance of the analytical method based on the differential approach for the quantification of measurement uncertainty and on the comparison of recovery associated with each one of the analytical steps whose performance can vary with the analyte origin, for spiked and incurred samples.This approach was applied to the determination of pesticide residues in apples. For the analytes covered, no evidence was found that the studied sample processing and extraction steps performance for this matrix varies with the analyte origins.     

Production and stability testing of incurred reference materials for the anabolic steroid trenbolone in bovine urine.

The production of stable reference materials with incurred residues of veterinary drugs is necessary for the validation of methods of analysis, including the determination of critical performance characteristics. A reference material for trenbolone in bovine urine was produced and the long-term stability was tested. From a pilot 16 week stability study on seven batches containing different additives it was concluded that the use of preservatives does not improve the stability of the residue. A final batch of reference material of 800 vials each containing 5 ml of urine with a target concentration of 5 micrograms l-1 was prepared. The homogeneity and long-term stability of the material were tested. The material was found to be homogeneous. Based on the results of a 52 week stability study it was concluded that the material is stable, using the current analytical methodology. For the development of reference materials, highly accurate and precise analytical methods are necessary. However, the current analytical methodology is not suitable for full evaluation and certification. Currently, a new LC-MS method is being developed. After validation of this method, the stability and homogeneity study will be repeated.     

Reliability‐targeted HPLC–UV method validation—A protocol enrichment perspective

Method validation is important in analytical chemistry to obtain the reliability of an analytical method. Guidelines provided by the regulatory bodies can be used as a general framework to assess the validity of a method. Since these guidelines do not focus on the reliability of analytical results exclusively, this study was aimed to combine a few recently evolved strategies that may render analytical method validation more reliable and trustworthy. In this research, the analytical error function was determined by appropriate polynomial regression statistics that determine the range of analyte concentration that may lead to more accurate measurements by producing the least possible total error in the assay and can be regarded as a reliable weighting method. The reliability of the analytical results over a particular concentration range has been proposed by a Bayesian probability study. In order to ensure the applicability of this approach, it was applied for the validation of an HPLC–UV assay method dedicated to the quantification of cefepime and tazobactam in human plasma. A comparison between the newer approach and the usual method validation revealed that the application of analytical error function and Bayesian analysis at the end of the validation process can produce significant improvements in the analytical results.     

色谱类分析仪器性能确认用标准物质的筛选

分析仪器验证是制药、食品、环境等多个行业实验室质量管理的重点,为解决我国色谱类分析仪器验证评价体系中缺乏统一标准物质的问题,提出了筛选性能确认行业推荐用标准物质的原则。通过分析不同行业色谱类分析仪器标准物质使用情况和国家标准及有证标准物质的发布现状,以筛选原则为指导,筛选出93种高效液相色谱性能确认用标准物质。为保证分析仪器的稳定性和可靠性提供了标准依据。     

Direct determination of nickel in petroleum by solid sampling–graphite furnace atomic absorption spectrometry

A procedure for the direct GFAAS determination of Ni in petroleum samples using a solid sampling strategy is proposed. Palladium was used as conventional modifier. Central composite design multivariate optimization defined the optimum temperature program and the Pd mass, allowing calibration using aqueous analytical solution. The limit of detection (LOD) at the optimized conditions was 0.23 ng of Ni, for typical sample masses between of 0.10 and 0.60 mg. Linearity at least up to 11 ng of Ni and a characteristic mass of 45 pg were observed, defining a dynamic range between 0.52 and 110 μg g⁻¹. Typical coefficients of variation (n = 10) in the analysis of oil reference materials were 7%. Method validation was performed both by the analysis of oil certified reference materials and by comparison with an independent method (ASTM 5863-B). No statistically significant difference was observed between obtained and expected values. The total determination cycle lasted 5 min, equivalent to a sample throughput of 6 h⁻¹ for duplicate determinations.     

Test of the generalized standard addition method and linearization algorithms for the direct,simultaneous, multi-element analysis of solid samples by electrothermal atomic absorption spectrometry

The application of a multi-element electrothermal atomic absorption spectrometry (ETAAS) instrument with line sources and Zeeman-effect background correction to the direct, simultaneous determination of Ag, Cd, Cr and Pb in solid reference materials is described. Due to the occurrence of interference effects, the generalized standard addition method (GSAM) was required for calibration purposes. In order to extend the dynamic range for analytes present at high concentrations, linearization algorithms were tested. The combination of the GSAM and extension of the linear range, when necessary, generally yielded acceptable analytical results for the suite of elements studied, and may provide a useful approach to calibration in the direct analysis of solid samples by multi-element ETAAS. However, while linearization yielded good results for Ag and Cd in solid reference materials, it remains to be demonstrated that acceptable performance can be obtained for other elements in real samples.     

Quality assurance program for the chemical characterization of soils

A quality assurance program has been developed both to assess and to demonstrate the quality of the results produced by an analytical diagram applied to the chemical characterization of soils. The composition of several soils was determined following procedures based on the methods that are applied to silicate materials. A combination of acid decomposition followed by fusion allows the determination of SiO₂, Al, Fe, Ca, Mg, Ti, P, Mn, Cd, Co, Cr, Cu, Ni, Pb and Zn; a specific acid attack was used for Hg analysis and an acid mixture decomposition to analyse Na, K, Li and Sr. Several quality control parameters, namely calibration function characteristics, limits of detection, limits of quantification, quality control standards, duplicate analysis, spike recoveries and certified reference materials analysis, are introduced, evaluated and discussed. The results obtained for the certified reference materials show that the analytical diagram gave acceptable accurate values for the elements applying the quality assurance program proposed.     

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     

Comparison of three strategies to evaluate uncertainty from in-house validation data. A case study: mercury determination in sediments

In the present paper, three approaches are compared for the evaluation of the combined uncertainty in the determination of mercury in aquatic sediments by an aqua regia extraction procedure. For this, the data obtained in validation studies from five certified reference materials (CRMs), covering a range of concentrations from 0.8 to 130 mg kg⁻¹ of mercury and analysed by three atomic spectroscopic techniques (cold vapour generation atomic fluorescence spectrometry, CV-AFS, cold vapour generation atomic absorption spectroscopy, and inductively coupled plasma mass spectroscopy), were considered. The combined uncertainty was firstly assessed by considering separately the data obtained for each CRM analysed (approach A). Moreover, this assessment was also performed with two other calculation approaches (B and C) based on the pooled data obtained from the validation step. The comparison of the results obtained for the different techniques showed a clear bias effect when using CV-AFS with nitric acid as a diluent. In relation to the strategies tested for the combined uncertainty assessment, approach C proved to be the easiest and friendliest method for uncertainty assessment.      

Quality-control materials in the USDA National Food and Nutrient Analysis Program (NFNAP)

The US Department of Agriculture (USDA) Nutrient Data Laboratory (NDL) develops and maintains the USDA National Nutrient Databank System (NDBS). Data are released from the NDBS for scientific and public use through the USDA National Nutrient Database for Standard Reference (SR) (). In 1997 the NDL initiated the National Food and Nutrient Analysis Program (NFNAP) to update and expand its food-composition data. The program included: 1) nationwide probability-based sampling of foods; 2) central processing and archiving of food samples; 3) analysis of food components at commercial, government, and university laboratories; 4) incorporation of new analytical data into the NDBS; and 5) dissemination of these data to the scientific community. A key feature and strength of the NFNAP was a rigorous quality-control program that enabled independent verification of the accuracy and precision of analytical results. Custom-made food-control composites and/or commercially available certified reference materials were sent to the laboratories, blinded, with the samples. Data for these materials were essential to ongoing monitoring of analytical work, to identify and resolve suspected analytical problems, to ensure the accuracy and precision of results for the NFNAP food samples.     

CSEARCH-STEREO: A new generation of NMR database systems allowing three-dimensional spectrum prediction

 A new method for spectrum prediction is presented permitting incorporation of stereochemical features, which highly improves the quality of the obtained chemical shift values. The method is based on comparison of the query-structure with a reference library of ring skeletons, so that stereochemical interactions can be counted. The number of stereochemical interactions obtained over a five-bond sphere is used to produce a three-dimensional HOSE-code leading to a more accurate spectrum prediction. The advantages of this new concept will be discussed using examples from natural product chemistry. Received: 25 October 1996/Revised: 20 March 1997/Accepted: 29 March 1997     

EQRAIN: uranium and plutonium interlaboratory exercises from 1997 to 2016—comparison to ITVs-2010

Since 1987, the CEA’s Committee for the establishment of analysis methods (CETAMA) has regularly implemented interlaboratory comparisons, entitled “evaluation of the quality results of analysis in the nuclear industry” (EQRAIN). Notably, the EQRAIN U and EQRAIN Pu interlaboratory comparisons assess proficiency in measuring a mass content of uranium or plutonium in reference solutions. This paper presents the results of measurement uncertainty assessments from EQRAIN U and EQRAIN Pu comparisons over 20 years of exercises (1997–2016). The mathematical approach developed in this work allowed to estimate the impact of short-term systematic and random errors to the overall uncertainty of each analytical method used in the interlaboratory comparison program. This statistical analysis shows a good consistency between measurement uncertainty values from EQRAINs and the measurement uncertainty target values established by the International Atomic Energy Agency for nuclear material balances (ITVs-2010).

     

Trace element determination in a mussel reference material using short irradiation instrumental neutron activation analysis

The production of certified reference materials in Brazil, and the consequent availability to national end users, is an important task for the enhancement of Metrology in Chemistry status in the country, as these materials are used for method validation, equipment calibration and for establishing metrological traceability links. In this study, Instrumental Neutron Activation Analysis (INAA) was applied to the determination of bromine, chlorine, magnesium, manganese, potassium and vanadium in a mussel reference material produced at IPEN-CNEN/SP. For the determination of these elements via the comparative INAA method, the respective analytical radionuclides, ⁸⁰Br, ³⁸Cl, ²⁷Mg, ⁵⁶Mn, ⁴²K and ⁵²V, are short lived and then, short irradiations are used. Six subsamples from two bottles of the Perna perna mussel reference material were analyzed. Each subsample was simultaneously irradiated with elemental standards for 10 s at the IEA-R1 research nuclear reactor through a pneumatic transfer system. After suitable decay periods, gamma radioactivity measurements were carried out, using a hyperpure germanium detector. The accuracy of the method was checked by using the NIST SRM 1566b–“Oyster Tissue” certified reference material. The comparison of the results obtained in this study to the robust mean of the interlaboratorial collaborative trial used for the characterization of the mussel reference material was performed via z-score tests. The comparison showed that the short irradiation INAA method is suitable for the characterization of new reference materials.