Primary reference material

Comparison of test values with a conventional true value ( reference value ) of a (certified) reference material (RM, CRM). In method development and validation of analytical procedures, the comparison of experimental results with standards of diverse kind (laboratory standards, certified reference materials, primary standards) plays an essential role. The decision as to whether an experimental result hits the reference value depends not only from the result itself but also from its uncertainty interval. 

There is often some confusion between the terms standards and reference materials. Primary standards represent the top-tier of chemical standards and, in principle, provide a means of establishing the traceability of analytical data to the SI measurement units (e.g., the kilogram, mole, meter, and second). A limited number of pure chemicals are recognized as primary standards (and thus can constitute certified reference materials). Most certified reference materials are not of themselves primary standards rather, the property values assigned to them are traceable to primary standards where practical. 

Key words Traceability Certified reference materials Primary methods Analytical chemistry... 

A motor fuel has an octane number X if it behaves under tightly defined experimental conditions the same as a mixture of X volume % of isooctane and (100 - X)% of n-heptane. The isooctane-heptane binary mixtures are called primary reference fuels. Octane numbers higher than 100 can also be defined the reference material is isooctane with small quantities of tetraethyl lead added the way in which this additive acts will be discussed later. 

National Institute of Standards and Technology (NIST). The NIST is the source of many of the standards used in chemical and physical analyses in the United States and throughout the world. The standards prepared and distributed by the NIST are used to caUbrate measurement systems and to provide a central basis for uniformity and accuracy of measurement. At present, over 1200 Standard Reference Materials (SRMs) are available and are described by the NIST (15). Included are many steels, nonferrous alloys, high purity metals, primary standards for use in volumetric analysis, microchemical standards, clinical laboratory standards, biological material certified for trace elements, environmental standards, trace element standards, ion-activity standards (for pH and ion-selective electrodes), freezing and melting point standards, colorimetry standards, optical standards, radioactivity standards, particle-size standards, and density standards. Certificates are issued with the standard reference materials showing values for the parameters that have been determined. 

The history of reference materials is closely linked with the development of analytical chemistry. In the 19th Century all chemicals were, in comparison with those of today, of poor purity. Thus, for volumetric analysis suitable purified materials as primary standards had to be specified. One of the first examples was the recommendation of As(III) oxide by Gay-Lussac (1824) for this purpose. Somewhat later, Sorensen (1887) proposed criteria for the selection of primary chemical standards. These were further elaborated by Wagner (1903) at the turn of the last century. It is worthwhile mentioning that their criteria were quite similar to those used today. 

Much of the early work with certified reference materials was linked to the derivation of reference methods and there was a period in which primary or definitive (i.e. very accurate but usually very complex) and secondary (or usable) methods were reported e.g. steroid hormones (Siekmann 1979), creatinine (Siekmann 1985), urea (Welch et al. 1984) and nickel (Brown et al. 1981). Although there are some application areas, such as checking the concentrations of preparations listed in a pharmacopoeia, where a prescribed, defined method has to be used, in practice such work is limited. However, this approach to chemical analysis is no longer widely used and will not be further discussed. The emphasis now is placed on using RMs to demonstrate that a method in use meets analytical criteria or targets deemed to be appropriate for the application and to develop figures of merit (Delves 1984). 

The primary purposes for which reference materials are employed are encompassed within the laboratory Quality Assurance Procedures. Quality assurance comprises a number of management responsibilities which focus on how the laboratory is organized, how it deals with situations, how it interacts with users, together with analytical responsibilities re internal quality control and external quality assessment (Sargent 1995 Burnett 1996). Ideally each component follows a documented protocol and written records of all activities are maintained. 

Filter samples can be prepared to airborne workplace concentrations by spiking each filter with aqueous solution containing elements with concentrations gravimetrically traceable to ultrapure metals or stoidiiometricaUy well defined oxides. The amormts correspond for some of the materials to current threshold limit values of contaminants in workroom atmospheres provided that the simulated filter has been exposed to one cubic meter of air. The certified values are based on a gravimetric procedure, i.e. weight per volume composition of the primary reference material dissolved in high purity sub-dis-tiUed acids. The National Institute of Occupational Health in Oslo, Norway, has produced several batches of such materials certified for 20 elements. Additionally, information values are reported for four other elements see Table 6.2. 

Primary reference materials, i.e. international or national certified reference materials, CRMs)... 

New exploration techniques, and new reference materials in support of them, were needed. One major change was in the use of ore pathfinder elements, rather than the ore elements themselves, for exploration purposes. For example, instead of analyzing samples for the primary Au ore element, samples were analyzed for As, Hg, and W pathfinders that pointed to hidden gold deposits. The pathfinder elements occur in association with ore veins, but have a much broader spread than the mineralized area itself. However, measurement of the pathfinder elements requires methods with better detection limits than were needed in earlier exploration programs, as the pathfinders typically are not as enriched as the ore elements, in comparison to baseline crustal levels. 

Accuracy of in vivo and in vitro measurements of americium is determined through the use of standard, certified radioactive sources with known concentrations of americium. The primary source of certified americium standards is the National Institute of Standards and Technology (NIST). Standard solutions are available for241 Am (SRM 4322, 40 Bq/g [1.1 nCi/g]) and 243Am (SRM 4332, 40 Bq/g [1.1 nCi/g]). Standard Reference Materials for human lung (SRM 4351) and human liver (SRM 4352) are also available from NIST. 

Conventional XRF analysis uses calibration by regression, which is quite feasible for known matrices. Both single and multi-element standards are in use, prepared for example by vacuum evaporation of elements or compounds on a thin Mylar film. Comparing the X-ray intensities of the sample with those of a standard, allows quantitative analysis. Depending on the degree of similarity between sample and standard, a small or large correction for matrix effects is required. Calibration standards and samples must be carefully prepared standards must be checked frequently because of polymer degradation from continued exposure to X-rays. For trace-element determination, a standard very close in composition to the sample is required. This may be a certified reference material or a sample analysed by a primary technique (e.g. NAA). Standard reference material for rubber samples is not commercially available. Use can also be made of an internal standard,... 

More attention should be devoted to the quantitative determination of analytes in real-life samples. The accuracy of the determinations and the traceability of the overall analytical process are insufficiently ensured [120,121], As no primary methods are available for the purpose, this necessarily implies the use of certified reference materials. 

The application of PSA measurements for clinical monitoring of prostatic carcinoma requires fine tuning of PSA assays. One important aspect of this tuning is to have well-defined standards (primary calibrators). Calibrators or primary reference materials consisting of PSA complexed with ACT have been prepared and are available to sponsors of commercial immunoassays. As a result of this, some sponsors have studied calibration stability and have shown that calibration did not change within 14 to 90 days. Primary references of 90 percent PSA-ACT and 10 percent f-PS A have been shown to minimize differences in PSA measurements between different assays [NCCLS Document—Primary Reference Preparations Used to Standardize Calibration of Immunochemical Assays for Serum Prostate... 

It is important that a measurement made in one laboratory by a particular analyst can be repeated by other analysts in the same laboratory or in another laboratory, even where the other laboratory may be in a different country. We aim to ensure that measurements made in different laboratories are comparable. We are all confident that if we measure the length of a piece of wire, mass of a chemical or the time in any laboratory, we will get, very nearly, the same answer, no matter where we are. The reason for this is that there are international standards of length, mass and time. In order to obtain comparable results, the measuring devices need to be calibrated. For instance, balances are calibrated by using a standard mass, which can be traced to the primary mass standard (see also Chapter 5). The primary standard in chemistry is the amount of substance, i.e. the mole. It is not usually possible to trace all of our measurements back to the mole. We generally trace measurements to other SI units, e.g. mass as in 40 mg kg-1 or trace back to reference materials which are themselves traceable to SI units. 

Section 5.2 introduced the subject of metrological traceability and calibration and the use of pure chemical substances and reference materials in achieving trace-ability. Reference materials are used as transfer standards. Transfer standards are used when it is not possible to have access to national or international standards or primary methods. Transfer standards carry measurement values and can be... 

In the analysis of solid samples (e.g., LA-ICP-MS, SEM), synthetic standards cannot easily be prepared to the required concentrations, and accurate calibration of such techniques is often challenging. In some cases (e.g., SEM) pure element or single mineral standards are used, ideally with an appropriate standard for each element to be quantified. (It is possible in SEM, within limits, to use fewer standards than the number of elements to be determined, with the calibration for other elements being predicted from the response of the nearest element.) More often, however, multielement primary standards are used as the means of calibrating the instrument, e.g., for LA-ICP-MS of glasses, volcanics, and ceramics, two glass standards, NIST 610 and 612 (Pearce et al. 1996), are often used. It is always advisable to use more than one multielement standard in order to cover as wide a range of concentrations as possible, and to use at least one additional independent reference material as an unknown, for quality assurance purposes (see below). 

Alternatively, the combustion of a certified reference material can be used. Since 1934, benzoic acid has been the internationally accepted primary standard material for determination of the energy equivalent of oxygen-bomb calorimeters [39,40]. In this case,... 

Although most assays perform well with regard to specificity and reproducibility, the major problem remains their standardization (A9, Dl, K30, L4). There is currently no internationally accepted standard, and the selection of a reference material raised many problems (A8, G5, K30, L4). A number of questions have not been solved Should the standard consist of several apo(a) isoforms Can the reference material be lyophilized Should results be expressed as mass or as moles of apoprotein or lipoprotein How should the protein mass of the primary standard be determined What are optimal storage conditions for the secondary standard Which method can be used as a reference method Can recombinant apo(a) represent an alternative for a primary standard These problems came to light in the course of the international surveys whose results were presented at the Lp(a) Workshop in New Orleans (1992) (L4). 

Prior to the Seattle Workshop, several batches of seawater from Hawaii were distributed to attendees for analysis. It became immediately clear to workshop participants that the key to making valid comparisons was both a common reference material and a uniform blank solution (Hedges et al., 1993 Sharp, 1993). The primary source of discrepancy among analysts was poor blank control, not oxidative capacity. 

The primary and immediate need is for a trace metal reference material, but a certified reference material would provide even greater benefits. A technique based on isotope dilution with detection by inductively-coupled plasma mass spectrometry (ICP-MS) (Wu and Boyle, 1998) most clearly meets the traceability criteria required for a certified reference material. Although useful for iron and several other metals, isotope dilution is not possible for monoisotopic elements like cobalt, so other techniques must also be used. Indeed, it is advisable that several techniques be used to certify a trace metal reference material. 

Reference materials that represent the primary deep-sea and coastal depositional environments and biological materials would solve many of the problems that radiochemists face in analysis of sediments from these settings. Radiochemists require reference materials comprising the primary end member sediment and biological types (calcium carbonate, opal, and red clay from the deep-sea and carbonate-rich, silicate-rich, and clay mineral-rich sediments from coastal environments and representative biological materials). Additional sediment reference material from a river delta would be valuable to test the release of radionuclides that occurs as riverine particles contact seawater. 

A sample for which the true response is already known or is established is called a standard. A standard can be a primary standard, which is a standard through which other substances or solutions are made to be standards. It can also be a secondary standard, a solution whose concentration is known accurately either because it was prepared using a primary standard or because it was compared to another standard. All standards must ultimately be traced to a standard reference material (SRM). Standard reference materials are available from the National Institute of Standards and Technology (NIST) and should not be used for any other purpose in the laboratory (Section 5.4). Standardization is an experiment in which a solution is compared to a standard in order for itself to be a standard. The solutions used to establish a standard curve are often called reference standards and these must also be traceable to an SRM. 

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