Calibration materials

This example presents four analytical situations (a) good control, (b) sudden shift in accuracy - perhaps the calibration material has become contaminated, (c) a gradual shift in accuracy-perhaps a reagent has exceeded its expiry date, (d) very poor precision - perhaps an autosampler is working erratically. 

Rossbach M, Ostapczuk P, Emons H (1998) Microhomogeneity of candidate reference materials Comparison of solid sampling Zeeman-AAS with INAA. Fresenius J Anal Chem 360 380-383. Rossbach M, Stoeppler M (1987) Use of CRMs as mutual calibration materials and control of synthetic multielement standards as used in INAA. J Radioanal Nud Chem Artides 113 217-223. Sargent M (1995) Development and application of a protocol for quality assurance of trace analysis. Anal Proc 32 71-76. 

Cl and El are both limited to materials that can be transferred to the ion source of a mass spectrometer without significant degradation prior to ionisation. This is accomplished either directly in the high vacuum of the mass spectrometer, or with heating of the material in the high vacuum. Sample introduction into the Cl source thus may take place by a direct insertion probe (including those of the desorption chemical ionisation type) for solid samples a GC interface for reasonably volatile samples in solution a reference inlet for calibration materials or a particle-beam interface for more polar organic molecules. This is not unlike the options for El operation. 

This latter point begs the question Who can verify the accuracy of a reference point if its value may vary In other words, who is the ultimate source of calibration materials, such as a thermometer In the U.S., it is the National Institute of Standards and Technology (NIST). This is the same organization that we cited as the source of accurate standardization materials in Chapters 3 and 4. Experiments 16 and 17 in this chapter are exercises in the calibration of a temperature sensor and how such a calibrated sensor can be used. 

An alternative to the common device of determining relative intensities is a study of the fine structure of the scattered beam. This entails resolving the spectrum of scattered light into its three peaks, viz. a central peak and two side ones. The need is thus obviated to refer to I0 or, according to the apparatus, the scattering power of a standard calibration material. The method is used mainly for determining diffusion constants and thermodynamic properties of liquids. 

Another possibility is to choose expert laboratories, which are able to measnre with high precision reference methods, ntilising traceable calibration materials. If these laboratories use methods based on different physieo-chemical principles and eome to more or less the same result, it is very probable that the value is elose to the true value. 

FIGURE 16.9 Schematic representation of principle of the molar mass calculation from the SEC chromatogram. The linear or polynomial calibration dependence log M vs. or log M [t ] vs. Er is obtained with help of the narrow molar mass distribution calibration materials (Section 16.8.3). The heights indicate concentration of each fraction i within sample (c =hJYh. The advanced computer software considers rather the areas of segments than their heights. The molar mass for each or segment i is taken from the calibration dependence. 

As explained in Sections 16.3.4, 6.4.1, and 16.4.2, SEC is a nonabsolute method, which needs calibration. The most popular calibration materials are narrow molar mass distribution polystyrenes (PS). Their molar mass averages are determined by the classical absolute methods—or by SEC applying either the absolute detection or the previously calibrated equipment. The latter approach may bring about the transfer and even the augmentation of errors. Therefore, it is recommended to apply exclusively the certified well-characterized materials for calibrations. These are often called PS calibration standards and are readily available from numerous companies in the molar mass range from about 600 to over 30,000,000g moL. Their prices are reasonable and on average (much) lower than the cost of other narrow MMD polymers. Other available homopolymer calibration materials include various poly(acrylate)s and poly(methacrylate)s. They are, similar to PS, synthesized by anionic polymerization. Some calibration materials are prepared by the methods of preparative fractionation, for example, poly(isobutylene)s and poly(vinylchloride)s. 

It is necessary to say that the molar masses of the calibration materials quoted by some suppliers may differ from the actual values. In other words, some commercial calibration materials may jump out from the calibration dependences because their molar mass determined by the producer is wrong. 

These materials, however, as a rule exhibit rather broad chemical composition distribution. Block copolymers may contain important amounts of parent homopolymer(s) [232,244,269], In any case, it is to be kept in mind that practically all calibration materials contain the end groups that differ in the chemical composition, size, and in the enthalpic interactivity from the mers forming the main chain. In some cases, also the entire physical architecture of the apparently identical calibration materials and analyzed polymers may differ substantially. The typical example is the difference in stereoregularity of poly(methyl and ethyl methacrylate)s while the size of the isotactic macromolecules in solution is similar to their syndiotactic pendants of the same molar mass, their enthalpic interactivity and retention in LC CC may differ remarkably [258,259]. 

Numerous information on various polymers can be found for example in Polymer Handbook [37] and on the particular calibration materials in the monographs [23-25,30]. 

Facility and equipment design Equipment maintenance Equipment cleaning Calibration Materials control... 

In this chapter I use the term metrological traceability to refer to the property of a measurement result that relates the result to a metrological reference. The word metrological is used to distinguish the concept from other kinds of traceability, such as the paper trail of documentation, or the physical trail of the chain of custody of a forensic sample. When the term traceable standard is used to refer to a calibration material, for example, the provenance of the material is not at issue, but the quantity value embodied in the standard. 

Laboratory personnel commonly give one of three common responses to someone who points out the traceability requirements of ISO/fEC 17025 Its ok we have our balances calibrated every year, and when it is further pointed out that calibration extends to the chemical aspects of the measurement, I am sure it is ok to use this analytical-reagent-grade material to make a calibration solution, or we make measurements in such complex matrices, a suitable CRM just does not exist. The first comment stems from the rather physical or engineering flavor of the section in ISO/IEC 17025 (section 5.6) (ISO/IEC 2005), although traceability of calibration materials is mentioned. 

The second response about the source of the calibration material is more difficult to deal with, because the truth is that the measurements being made are almost certainly not metrologically traceable. Faith in a percentage pu-... 

Perhaps if you have a resourceful and supportive national measurement institute, you might be able to persuade it to organize an interlaboratory certification to provide appropriate calibration materials, as has been done in Australia by the grain industry for protein measurements. 

Each echo has traveled a distance twice the cell length d further than the previous echo and so the velocity can be calculated by measuring the time delay t between successive echoes c = 2d/t. The cell length is determined accurately by calibration with a material of known ultrasonic velocity, e.g. distilled water 2d = cw.tw (where the subscripts refer to water). The attenuation coefficient is determined by measuring the amplitudes of successive echoes A = A0e-2cxd, and comparing them to the values determined for a calibration material. A number of sources of errors have to be taken into account if accurate measurements are to be made, e.g., diffraction and reflection (see below). 

GMP touches on all facets of drug manufacture. Personnel must be properly qualified for their tasks. The building should be adequately equipped in terms of utilities, air quality, and sanitation. All manufacturing machinery and equipment must be properly and regularly maintained, cleaned, and calibrated. Materials used in the manufacture of an active pharmaceutical ingredient (API) should be monitored for quality. Many additional aspects of drug manufacture are addressed by GMP. Implementation of GMP is the problem of the manufacturer. GMP does not specify how different aspects of manufacture should be handled. GMP states only that the aspects must be addressed systematically. 

A calibration hierarchy must be defined to allow metrological traceability, preferably to a unit of the International System of Units (SI). Traceability involves plugging into a reference measurement system of reference procedures and commutable calibration materials. 

There are two major reasons why a traceability chain may be broken and trueness lost due to the introduction of bias insufficient commutability of a calibration material and non-specificity of a measurement procedure. The effect of these separate properties are often indiscriminately lumped together as matrix effect . Commutability refers to the ability of a material, here a calibrator, to show the same relationships between results from a set of procedures as given by routine samples [16, 17]. Analytical specificity refers to the ability of a measurement procedure to measure solely that quantity which it purports to examine [16, 18]. Discrepancies between results of a reference procedure and a routine procedure applied to routine samples are often caused by non-specificity of the routine procedure. The use of a set of human samples as a manufacturer s calibrator to eliminate so-called matrix effects should only be accepted if the relationship between the results from reference and routine procedures is sufficiently constant to allow explicit correction with consequent increased uncertainty of assigned values. 

A reference material (RM) for traceability of total protein in human urine does not exist. The control materials used in clinical laboratories for calibration purposes are not unified. Some laboratories use bovine serum albumin as a calibration material (URINE-CHIMIE BIOTROL) [5], whereas others use a mixture of human serum albumin (70%) and globulin (30%) (LYPHOCHECK Quantitative Urine Control, BIO-RAD) [6]. The use of various protein calibration standards yields various results of... 

Pure organic substance, including certification or provision of natural or iso-topically enriched single substance calibration materials... 

Achieving traceability in ISO 17025 accredited laboratories clearly demands more than just provision of suitable calibration materials or values. Hence, traceability demonstrator projects are being undertaken to identify issues, best practice, and key areas to address. It is also necessary to transfer methodology and expertise to UK reference laboratories and to provide guidance on implementation of traceability to UK... 

Ion suppression is so far mainly considered in the context of sensitivity and the lower limit of quantification of an assay. But it has to be emphasized that short term variations in ion yields—particularly due to matrix components—can compromise the accuracy of analyses Whenever the variation of ion yield has a differential impact on target analyte and internal standard, accuracy is compromised. This means that the reliability of LC-MS/MS analyses critically depends on (1) how similar the impact of ion suppression or ion enhancement on target analyte and internal standard compound is and on (2) how similar the matrices of calibrator samples and actual patients samples are with respect to the modulation of ionization efficacy. This problem can be of relevance for an entire measuring series—if systematic differences in the ionization modulation properties of calibration materials and actual patients samples are present—or it may non-systematically affect individual patients samples as well. 

A fundamental requirement for LC-MS/MS calibration materials is that matrix effects exerted by these materials are most similar to the matrix effects exerted by actual patients sample materials. Lyophilisation, virus inactivation and other procedures applied during the industrial production of calibration and control materials, may notably impact the ionization behaviour of extracts from such samples and can result in differential matrix effects in calibrators and actual patients samples. If the internal standard peak areas found for calibration samples systematically differ from those found in patients samples, inappropriateness of the calibration materials should be suspected. However, we have previously observed that calibration materials from different commercial sources lead to inaccurate tacrolimus results in an instrument specific manner, without showing deviations in the internal standard peak area. This effect was most likely related to ionization enhancement affecting the target analyte but not the homologue internal standard (ascomycin) ionization and being restricted to calibrator samples. This resulted in systematically low tacrolimus results of clinical samples in one instrument for one specific calibrator lot [52],... 

Vogeser M (2008) Instrument-specific matrix effects of calibration materials in the LC-MS/ MS analysis of tacrolimus. Clin Chem 54 1406-1408... 

Calculation procedure. Defined amounts of the material under analysis and the calibration material with known contents of a standard compound are injected separately and chromatographed under identical conditions, thus giving chromatograms with peaks of compound i and s having the areas Aj and A, respectively. The results are calculated by using the equation... 

All of the above techniques can be employed to analyse materials in any state, i.e., gases, liquids and even solid compounds. Also procedure are conceivable in which the material under analysis and the calibration material have different states of aggregation. 

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