Traceability in laboratory medicine

In laboratory medicine meaningful measurements are essential for diagnosis, risk assessment, treatment and monitoring of patients. Thus methods applied in diagnostic measurements must be accurate, precise, specific and comparable among laboratories. Inadequate or incorrect analytical performance has consequences for the patients, the clinicians, and the health care system. One key element of metrology is the traceability of a measurement result to the SI system ensuring comparable results. This principle is described in the ISO/TC 212/WG2 N65 prEN 17511 Standard. In addition to the principles of metrology, the clinical usefulness, the diagnostic needs, and the biological and disease associated variations in patients' specimens have to be considered when the analytical biases for diagnostic purposes are defined. It must be the general goal of diagnostic laboratories to produce results that are true and comparable worldwide. The recent European in vitro diagnostic (IVD) Directive 98/79 EC follows the above mentioned standard of the International Organization for Standardization (ISO) and the European Committee for Standardization (CEN) requesting its application for all IVD reagents used within the European Union. This new European legislation will have a worldwide impact on manufacturers and clinical laboratories and will be implemented in 2003. It states that "traceability of values assigned to calibrators and/or control materials must be assured through available reference measurement procedures and/or available reference materials of a higher order". Thus a worldwide reference system needs to be established by collaboration and mutual recognition between the United States National Institute of Standards and Technology (NIST), European Metrology Institutes (EUROMET), regulatory bodies (e.g. United States Food and Drug Administration, FDA) the IVD industry and professional organizations (e.g. International Federation of Clinical Chemistry and Laboratory Medicine, IFCC). In June 2002, in Paris, representatives of international and regional organizations and institutions decided to form the "Joint Committee on Traceability for Laboratory Medicine" (JCTLM), which will support industry in registration and licensing of the "CE" label to test systems conforming to the IVD Directive.Presented at the International ILAC/IAF Conference on Accreditation in Global Trade, 23–25 September 2002, Berlin, Germany     

Validation of high-performance liquid chromatography methods for pharmaceutical analysis. Understanding the differences and similarities between validation requirements of the US Food and Drug Administration,the US Pharmacopeia and the International Conference on Harmonization

One of the most critical factors in developing pharmaceutical drug substances and drug products today is ensuring that the HPLC analytical test methods that are used to analyze the products generate meaningful data. The US Food and Drug Administration (FDA) and United States Pharmacopeia (USP) have each recognized the importance of this to the drug development process and have separately increased validation requirements in recent years. A third source, the International Conference on Harmonization (ICH), has added requirements that, when combined with the previous two sources, have led to three different sets of validation requirements leaving the industry in a state of confusion. This paper is written to clear up the confusion over the validation requirements that are presented by each of these three sources.     

Forensic examination of ink by high-performance thin layer chromatography--the United States Secret Service Digital Ink Library

Forensic examinations of ink have been performed since the beginning of the 20th century. Since the 1960s, the International Ink Library, maintained by the United States Secret Service, has supported those analyses. Until 2009, the search and identification of inks were essentially performed manually. This paper describes the results of a project designed to improve ink samples' analytical and search processes. The project focused on the development of improved standardization procedures to ensure the best possible reproducibility between analyses run on different HPTLC plates. The successful implementation of this new calibration method enabled the development of mathematical algorithms and of a software package to complement the existing ink library.     

The International Atomic Energy Agency's program on analytical quality control

For more than thirty years the International Atomic Energy Agency has been assisting laboratories in Member States in maintaining and improving the reliability, i.e. the quality of analyses of nuclear, industrial, environmental and biological materials, and materials of marine origin. Through the Analytical Quality Control Services (AQCS) the Agency initiates and supports improvements in the accuracy of analytical chemical and radiometric measurements and their traceability to basic standards. This is achieved by organizing worldwide and regional intercomparison exercises and by distributing reference materials. The latest biological and environmental reference and intercomparison materials are presented and general information is given on the preparation of materials, intercomparison runs, and the evaluation of reference data. Means to improve the quality of intercomparison results are presented and discussed.     

Characterization of NIST food-matrix standard reference materials for their vitamin C content

The vitamin C concentrations in three food-matrix Standard Reference Materials (SRMs) from the National Institute of Standards and Technology (NIST) have been determined by liquid chromatography (LC) with absorbance detection. These materials (SRM 1549a Whole Milk Powder, SRM 1849a Infant/Adult Nutritional Formula, and SRM 3233 Fortified Breakfast Cereal) have been characterized to support analytical measurements made by food processors that are required to provide information about their products’ vitamin C content on the labels of products distributed in the United States. The SRMs are primarily intended for use in validating analytical methods for the determination of selected vitamins, elements, fatty acids, and other nutrients in these materials and in similar matrixes. They can also be used for quality assurance in the characterization of test samples or in-house control materials, and for establishing measurement traceability. Within-day precision of the LC method used to measure vitamin C in the food-matrix SRMs characterized in this study ranged from 2.7 % to 6.5 %.     

IAEA Programme of natural matrix reference materials for the determination of radionuclides

Summary The International Atomic Energy Agency has been providing analytical quality control services (AQCS) to its Member States since the 1960's. The AQCS programme distributes reference materials (RMs), organizes intercomparison runs, and provides training courses for quality assurance in chemical analysis and radioactivity measurements of food, biological, environmental and marine materials. This paper focusses on those aspects of the subject dealing with reference materials and intercomparison runs for the determination of radionuclides. Nineteen natural matrix reference materials are available for the determination of radionuclides. Twelve new intercomparison and reference materials are in preparation or under consideration. The radionuclides of interest include: K-40, Mn-54, Co-60, Sr-90, Tc-99, Ru-106, Ba-133, Cs-134, Cs-137, Pb-210, Ra-226, Th-228, Th-232, Pu-238, Pu-239+240.     

The development and certification of Standard Reference Materials® (SRMs) to assess and ensure accurate measurement of Pb in the environment

The National Institute of Standards and Technology (NIST) has had a major quality-assurance role in the federal effort to reduce lead poisoning of children in the United States through its mission of ensuring the accuracy of chemical measurements. NIST certifies reference materials (standard reference materials – SRMs) that are used to benchmark measurements by secondary and field methods of analysis – to ensure that decisions of great health and economic impact are soundly based on good measurement science. Over the past 10 years, in cooperation with the US Environmental Protection Agency (EPA), US Department of Housing and Urban Development (HUD), and the United States Geological Survey (USGS), NIST has prepared and certified SRMs for lead content in soil, indoor dust, and paint. The role of these materials in meeting regulatory and abatement needs is described and their certified values are summarized.     

The development and certification of Standard Reference Materials (SRMs) to assess and ensure accurate measurement of Pb in the environment

The National Institute of Standards and Technology (NIST) has had a major quality-assurance role in the federal effort to reduce lead poisoning of children in the United States through its mission of ensuring the accuracy of chemical measurements. NIST certifies reference materials (standard reference materials--SRMs) that are used to benchmark measurements by secondary and field methods of analysis--to ensure that decisions of great health and economic impact are soundly based on good measurement science. Over the past 10 years, in cooperation with the US Environmental Protection Agency (EPA), US Department of Housing and Urban Development (HUD), and the United States Geological Survey (USGS), NIST has prepared and certified SRMs for lead content in soil, indoor dust, and paint. The role of these materials in meeting regulatory and abatement needs is described and their certified values are summarized.     

Metrology in chemistry: Rapid developments in the global metrological infrastructure, the CIPM MRA and its economic and social impact

Over the last decade, significant developments in metrology in chemistry have been observed, triggered by rapidly increasing demands by industry, trade, society, regulators, and accreditation bodies. Internal markets like the European Union, and trade agreements, like those agreed between the EU and the United States, Australia, Japan, and others will only really work when technical barriers to trade caused by non-harmonized measurement and testing systems and lack of international recognition of national measurement standards and certificates issued by the National Metrology Institutes have been taken away. Food safety test results and nutritional values, clinical and environmental measurements have to be comparable and reliable worldwide. Food products from all continents are traded year round on a global basis. Individuals are traveling everywhere. The environment and climate influences all of us.Electronic Supplementary Material Supplementary material is available for this article at Presented at International Symposium on Metrology in Chemistry, 2004 Beijing, China.     

Evaluation of Ge(Li) Compton suppression spectrometers for non-destructive radiochemical analysis

Ge(Li) Compton suppression spectrometers are evaluated relative to the specific needs of the analytical radiochemist. Their application to the analysis of radionuclides found in neutron activation, fission product, and environmental radionuclide analyses is discussed. This paper is based on work performed under United States Atomic Energy Commission Contract AT(45-1)-1830.     

Systemtheorie in der Analytik

International agreements, which partly have become law already, and the demand for uniformity and comparability of analytical informations make it necessary to redetermine certain definitions and designations in chemical analysis. Units and ranges of quantity (working range, ranges of sample quantity and content) are defined and denominated, aiming at a system which is logical in itself and also leads to optimum solutions of analytical problems. The relations between the defined ranges, recommendations for denomination of methods, the problems of statements in ppm and ppb as well as the useless statement of 0% as begin of a range for measurements are discussed. Conversion relations for content systems are given.     

A review of methods for the chemical characterization of cannabis natural products

Cannabis has garnered a great deal of new attention in the past couple of years in the United States due to the increasing instances of its legalization for recreational use and indications for medicinal benefit. Despite a growing number of laboratories focused on cannabis analysis, the separation science literature pertaining to the determination of cannabis natural products is still in its infancy despite the plant having been utilized by humans for nearly 30 000 years and it being now the most widely used drug worldwide. This is largely attributable to the restrictions associated with cannabis as it is characterized as a schedule 1 drug in the United States. Presented here are reviewed analytical methods for the determination of cannabinoids (primarily) and terpenes (secondarily), the primary natural products of interest in cannabis plants. Focus is placed foremost on analyses from plant extracts and the various instrumentation and techniques that are used, but some coverage is also given to analysis of cannabinoid metabolites found in biological fluids. The goal of this work is to provide a collection of relevant separation science information, upon which the field of cannabis analysis can continue to grow.     

Neutron Activation Analysis in the IAEA Projects on Air Pollution

The International Atomic Energy Agency (IAEA) has been promoting studies on air pollution since 1992. During the period 1992–1999 there have been six major co-ordinated research and regional technical co-operation projects in which 77 counterparts from 40 Member States actively participated. The studies supported by the IAEA have included ambient and workplace airborne particulate matter, the use of appropriate plant biomonitors and a series of laboratory intercomparison exercises in support to these projects. Recent and current IAEA projects in this field are reviewed in the light of the application of neutron activation analysis, which has been used as a major analytical technique by more than two thirds of the counterparts, and contributed also approximately two thirds of all analytical results for the intercomparison exercises.     

International Atomic Energy Agency's contributions to advances in nutritional and environmental metrology

For more than three decades the International Atomic Energy Agency (IAEA) has supported projects on food, nutrition and environment for strengthening the analytical capabilities in developing countries (DCs). Over time, such efforts have led to the development of proper study designs, harmonization of sampling protocols, adequate contamination control and evaluation of the suitability of competing analytical techniques for the determination of specific analytes. Collectively, these consistent IAEA initiatives have promoted harmonization of chemical measurements thus facilitating comparability of results of filed investigations. Importantly, the Agency's efforts have infused a measure of metrological awareness in measurements carried out in field studies, including physiological measurements. Nuclear and isotopic techniques have played an important role in reaching these goals by establishing reliable measurement processes for application in health care studies.     

Quantitative analysis of acetates in cigarette tobacco using solid-phase microextraction and gas chromatography-mass spectrometry

A method incorporating solid-phase microextraction (SPME) and gas chromatography-mass spectrometry for the headspace analysis of selected volatile organic compounds present in cigarette tobacco is developed and evaluated. Quantitative information on methyl, ethyl, n-propyl, isopropyl, isopropenyl, vinyl, and butyl acetates present in 29 different flavor variants (full, light, and ultra-light) of the top ten selling brands in the United States is presented. The concentrations of the various acetate analytes range from the low nanaogram to microgram levels per cigarette. Clear differences are observed in the concentrations of various acetates when comparing the levels in brands from different manufacturers. The SPME technique provides a method that allows high sample throughput, requires little sample preparation, and yields useful analytical information. High precision is obtained on multiple measurements of cigarettes from an individual pack, but lower precision levels are observed in general when comparing results obtained on the analysis of cigarettes from different packs of the same brand. The higher pack-to-pack variations may be due in part to product aging with a proportionate amount of evaporative loss of the relatively volatile acetates.     

Challenges and successes in using inductively coupled plasma mass spectrometry for measurements of tungsten in environmental water and soil samples

Military small arms ranges in the United States have been used for munitions training with tungsten rounds, which are comprised of powdered tungsten (W) pressed together with polymeric binders. As a result, W has been introduced into surface soils. The environmental and human health effects of W remain open questions. The US Army Corps of Engineers is responsible for environmental monitoring, site assessments, and cleanup of small arms ranges. This work requires routine measurements of tungsten in natural waters and soils. However, the existing sample preparation and analytical procedures were not specifically developed with W in mind for environmental analysis. Our work suggests modification of existing metal sample preparation and analytical procedures are necessary to accurately quantify W in environmental media. Our group has been actively conducting W measurements using inductively coupled plasma mass spectrometry (ICPMS), both with quadrupole and sector field ICPMS systems. We have used heavy rare earth elements and iridium as internal standards. For soils, the great majority of the W from small arms can be dissolved using acid leaching with HNO₃–H₃PO₄ mixtures; more rigorous preparations with fusion or HF digestions can also be used. In ICPMS analysis, the largest challenge involves dealing with the significant carry-over and memory of W in sample introduction systems. This ultimately limits measurement capabilities, particularly at sub-µg L^?1 levels. With careful attention to the sample and standards’ matrix constituents, and proper washout time, successful analysis is possible and ICPMS is clearly the preferred technique. A commercially available fluoropolymer sample introduction system exhibits significantly improved memory characteristics.     

The role of metrology in chemistry in the upholding of public health and food safety in Hong Kong

The Government Laboratory has been involved in the provision of analytical and advisory services since its formal establishment in 1913 in support of the needs of the community and the commitments of the Government of Hong Kong Special Administrative Region, China. One of the earliest areas of work involves the testing of food samples for maintenance of public health and food safety. Remarkable advances in technology in recent years coupled with the introduction of new policies and regulations, the launching of new international standards and requirements have all contributed to significant and ever-rising demand of accurate, specific, comparable and traceable measurements using the latest technologies for a wide variety of additives, contaminants, residues and genetically modified ingredients in food.Metrology, the science of measurement, has always played a key role in the development and validation of analytical methodologies in the Government Laboratory for the realization of its measurements to the highest level of accuracies and traceability to internationally recognized standards. Besides the application of the latest analytical technologies such as isotope dilution mass spectrometry, tandem mass spectrometry, real-time polymerase chain reactions, etc., the Analytical and Advisory Services Division of the Laboratory develops a quality assurance system in full compliance with the requirements of ISO/IEC 17025 and endeavours to ensure that every analytical methods are validated with the best applicable means and are fit for the intended purposes. In this presentation, the role and application of metrology in chemistry in the measurements pertaining to public health and food safety work undertaken by the Government Laboratory are discussed.Presented at International Symposium on Metrology in Chemistry, 2004 Beijing, China.     

Basic equations and uncertainties in isotope-dilution mass spectrometry for traceability to SI of values obtained by this primary method

A current interest in chemistry concerns traceability of analytical measurements to the International System of Units (SI) and the estimation of their uncertainties in accordance with principles of metrology, that is, measurement science. “Primary methods of measurement” achieve traceability to SI directly without intermediate reference standards or materials and without significant empirical correction factors. Isotope-dilution mass spectrometry should be regarded as such a method. It has the potential of smallest presently achievable uncertainties for analytical measurements directly or for the certification of reference materials including those with abnormal isotopic composition. A simple explanation of the method including its basic equations is given. Full uncertainty estimation is emphasized in terms of these equations. The wider use of concepts of metrology in chemistry is discussed.     

IAEA analytical quality assurance programmes to meet the present and future needs of developing countries

For many years the International Atomic Energy Agency (IAEA) has been promoting analytical quality assurance and quality control in its Member States with emphasis on measurands that are amenable to analysis by nuclear and related techniques, i.e. radionuclides, trace elements, and stable isotopes. This paper reviews briefly the rationale for some of these activities, particularly in relation to the needs of participants in developing countries arising out of co-ordinated research programmes, technical co-operation projects and global and regional networks. Emphasis is given to biological and environmental reference materials with a matrix of natural origin. Also described are some activities arising out of the requirements of ISO-25 and other relevant international quality standards.     

Results of two European interlaboratory studies for the determination of beta-agonists in various matrices.

Two Beta-Agonist Interlaboratory Studies, 5/96 and 11/97, were designed and evaluated according to the International Harmonised Protocol for the Proficiency Testing of (Chemical) Analytical Laboratories (ISO/REMCO N 280) jointly elaborated by ISO, IUPAC and AOAC. In the sense of proficiency testing, interlaboratory studies are part of external quality assurance systems. The Beta-Agonist Interlaboratory Studies 5/96 and 11/97 were intended to offer laboratories in the EU Member States an opportunity to check objectively their routine methods for the detection of beta-agonists and to demonstrate the reliability of their analytical results; 48 and 44 laboratories, respectively, all involved in official residue control, participated in the studies. Irrespective of the large number of satisfactory results achieved at higher concentration levels according to the z-score evaluation, the number of false negative results is still unsatisfactory. The results of both Beta-Agonist Interlaboratory Studies confirmed that comparability of analytical results is not yet ensured within the European residue control system.