Analytical measurements

Can you imagine going to court with results that you are not completely sure about in terms of validity and reliability Imagine the situation where you have been asked to attend the coroner s court in relation to a suspected drug overdose You are in the witness box and you are asked to confirm that your results indicate that John Doe may have died from an overdose of heroin. His family is in court and your answer is, I think so, but I can t really be sure it was heroin and I can t be sure about the amount exactly . Clearly, this answer is not acceptable and it would not take many appearances at court of this type for you to lose any credibility as an expert witness and to bring your laboratory into disrepute. In order to avoid these types of situations, it is normal for forensic laboratories to implement a set of principles that ensure that results are valid, reliable, and repeatable. This forms part of the company s overarching quality system (see Chapter 9). One of the ways in which a laboratory can ensure that measurement is valid and fit for purpose is to adopt the valid analytical measurement (VAM) system. 

The VAM system was introduced and developed by LGC in the 1980s and describes a set of six principles designed to promote best practice and provide valid data to customers through quality programmes. The VAM principles are available through the National Measurement System Chemical and 

Biological Metrology Web site. Not every laboratory calls its quality system a VAM system, but all credible laboratories will have a quality system in place. The six principles as described in VAM are discussed next. 

Tandem mass spectrometric reading exploits some specific features of butylated AC and AA. By fragmentation, the AC produce a prominent fragment ion at miz 85, common to all of them (see scheme in Fig. 5). When fragmented, the butylated A A produce a fragment which is in mass 102 Th less than the precursor ion, due to a loss of the neutral moiety corresponding to butyl formiate (see scheme in Fig. 5). 

Consequently, for AC profiles, the precursor ion scan for the product ion at mlz 85 is performed in the range m z 200-600 and with appropriate collision 

For AA profiles, a neutral loss scan of m/z 102 is collected in the range m/z 130-280 and with an appropriate collision energy. 

For the basic AA (citrulline, homocitrulline, ornithine), glycine and arginine, data are acquired in the multiple reaction monitoring (MRM) mode by monitoring specific transitions with specific collision energies as optimized for the specific instrument. 

With a suitable instrument, the above three acquisition experiments (precursor ion scan, neutral loss scan, and MRM) can be cycled as having during all the experiment time (usually between 2 and 3 min) the interleave of each of them. 

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When designing and evaluating an analytical method, we usually make three separate considerations of experimental error. First, before beginning an analysis, errors associated with each measurement are evaluated to ensure that their cumulative effect will not limit the utility of the analysis. Errors known or believed to affect the result can then be minimized. Second, during the analysis the measurement process is monitored, ensuring that it remains under control. Finally, at the end of the analysis the quality of the measurements and the result are evaluated and compared with the original design criteria. This chapter is an introduction to the sources and evaluation of errors in analytical measurements, the effect of measurement error on the result of an analysis, and the statistical analysis of data. 

Measurement of pH With the availability of inexpensive glass pH electrodes and pH meters, the determination of pH has become one of the most frequent quantitative analytical measurements. The potentiometric determination of pH, however, is not without complications, several of which are discussed in this section. 

Stewart, K. K. Plow Injection Analysis New Tools for Old Assays, New Approaches to Analytical Measurements, Anal Chem. 1983, 55, 931A-940A. 

The majoiity of the various analyte measurements made in automated clinical chemistry analyzers involve optical techniques such as absorbance, reflectance, luminescence, and turbidimetric and nephelometric detection means. Some of these ate illustrated in Figure 3. The measurement of electrolytes such as sodium and potassium have generally been accomphshed by flame photometry or ion-selective electrode sensors (qv). However, the development of chromogenic ionophores permits these measurements to be done by absorbance photometry also. 

Absorbance. Analyte measurements in clinical analyzers using Hquid reagents are most commonly performed by transmission of light, ie, by absorbance photometry or colorimetry (Fig. 3a). The Hquid to be analyzed is either held in a cuvette or passed through a flowceU having transparent walls. 

A predictive macromolecular network decomposition model for coal conversion based on results of analytical measurements has been developed called the functional group, depolymerization, vaporization, cross-linking (EG-DVC) model (77). Data are obtained on weight loss on heating (thermogravimetry) and analysis of the evolved species by Eourier transform infrared spectrometry. Separate experimental data on solvent sweUing, solvent extraction, and Gieseler plastometry are also used in the model. 

Design considerations and costs of the catalyst, hardware, and a fume control system are direcdy proportional to the oven exhaust volume. The size of the catalyst bed often ranges from 1.0 m at 0°C and 101 kPa per 1000 m /min of exhaust, to 2 m for 1000 m /min of exhaust. Catalyst performance at a number of can plant installations has been enhanced by proper maintenance. Annual analytical measurements show reduction of solvent hydrocarbons to be in excess of 90% for 3—6 years, the equivalent of 12,000 to 30,000 operating hours. When propane was the only available fuel, the catalyst cost was recovered by fuel savings (vs thermal incineration prior to the catalyst retrofit) in two to three months. In numerous cases the fuel savings paid for the catalyst in 6 to 12 months. 

Electron spectroscopic techniques require vacuums of the order of 10 Pa for their operation. This requirement arises from the extreme surface-specificity of these techniques, mentioned above. With sampling depths of only a few atomic layers, and elemental sensitivities down to 10 atom layers (i. e., one atom of a particular element in 10 other atoms in an atomic layer), the techniques are clearly very sensitive to surface contamination, most of which comes from the residual gases in the vacuum system. According to gas kinetic theory, to have enough time to make a surface-analytical measurement on a surface that has just been prepared or exposed, before contamination from the gas phase interferes, the base pressure should be 10 Pa or lower, that is, in the region of ultrahigh vacuum (UHV). 

Determinant A chemical metabolic product of the change in the body s chemistry caused by exposure to a pollutant. The level of determinant is measured in a biological sample collected from the exposed worker, and compared to the biological exposure index (BEI). Determination The analytical measurement of a pollutant. 

AAoisture determination is probably one of the most important and most widely used analytical measurements in the processing and testing of food products. It is of economic importance both to the consumer and to the food technologist. To the technologist, the moisture content is frequently an index of stability and quality of food, while to the consumer, it may serve as a measure of quantity as well as a measure of quality. 

Overall, the RDE provides an efficient and reproducible mass transport and hence the analytical measurement can be made with high sensitivity and precision. Such well-defined behavior greatly simplifies the interpretation of the measurement. The convective nature of the electrode results also in very short response tunes. The detection limits can be lowered via periodic changes in the rotation speed and isolation of small mass transport-dependent currents from simultaneously flowing surface-controlled background currents. Sinusoidal or square-wave modulations of the rotation speed are particularly attractive for this task. The rotation-speed dependence of the limiting current (equation 4-5) can also be used for calculating the diffusion coefficient or the surface area. Further details on the RDE can be found in Adam s book (17). 

Drastic oxidations of sulphoxides are used when analytical measurements of sulphur content are required. These methods usually lead to the formation of sulphate and occur via the formation of sulphones. These reactions will be discussed in Section III. 

Bob is particularly concerned that, although analytical chemistry forms a major part of the UK chemical industry s efforts, it is still not considered by many to be a subject worthy of special consideration. Consequently, experimental design is often not employed when it should be and safeguards to ensure accuracy and precision of analytical measurements are often lacking. He would argue that although the terms accuracy and precision can be defined by rote, their meanings, when applied to analytical measurements, are not appreciated by many members of the scientific community. 

As shown in Figure 3.12, around 10 cycles of the masses is required to define the peak shape accurately and allow precise analytical measurements to be made. 

External standard A method of relating the intensity of a signal from an analyte measured in an unknown to the amount of analyte present. This method consists of running a series of standards containing known amounts of the analyte independently from the samples to be determined. 

Definition and Uses of Standards. In the context of this paper, the term "standard" denotes a well-characterized material for which a physical parameter or concentration of chemical constituent has been determined with a known precision and accuracy. These standards can be used to check or determine (a) instrumental parameters such as wavelength accuracy, detection-system spectral responsivity, and stability (b) the instrument response to specific fluorescent species and (c) the accuracy of measurements made by specific Instruments or measurement procedures (assess whether the analytical measurement process is in statistical control and whether it exhibits bias). Once the luminescence instrumentation has been calibrated, it can be used to measure the luminescence characteristics of chemical systems, including corrected excitation and emission spectra, quantum yields, decay times, emission anisotropies, energy transfer, and, with appropriate standards, the concentrations of chemical constituents in complex S2unples. 

Prediction of the useful life, or the remaining life, of coatings from physical or analytical measurements presents many problems in data analysis and interpretation. Two important considerations are that data must be taken over a long period of time, and the scatter from typical paint tests is large. These considerations require innovative application of statistical techniques to provide adequate prediction of the response variables of interest. 

The model has been fed with data obtained by analytical measurements of the Isocyanate decrease, water concentration, carbon dioxide emission, etc. 

With a minimum of analytical measurements, the effect of several parameters on the curing of polyurethane coatings can be studied using the presented model. 

Waters Seawater (National Research Council Canada 1992) was collected in the North Atlantic Ocean at a depth of 10 m, 35 km southeast of Hahfax, Nova Scotia, Canada. The water was peristaltically pumped through cleaned polyethylene-hned ethyl vinyl acetate tubing and 0.45-pm acrylic copolymer filters. It was acidified to pH 1.6 with ultrapure nitric acid during its immediate transfer to 50-L acid-leached polypropylene carboys, previously conditioned with ultrapure water acidified to pH 1.6. The seawater was later homogenized in two linked 800-L polyethylene tanks in a clean room and immediately bottled in cleaned 2-L polyethylene bottles. Randomly selected bottles were used for analytical measurements. 

The literature on RM certification indicates that there are two broad types of approaches for the characterization of RMs (i) statistical, and (2) measurement. The statistical approach relies on the in-depth application of statistical calculations to a body of analytical results obtained from diverse exercises, often widely scattered and discordant. The approach based on measurement emphasizes laboratory measurement aspects and deals more in detail with various diverse analytical measure-... 

The natural matrix materials, which are similar to the actual environmental, clinical, food, or agricultural samples analyzed, are used to validate the complete analytical measurement process including extraction, cleanup and isolation procedures, and the final chromatographic separation, detection, and quantification. 

Kristiansen J, Christensen JM (1998) Traceability and uncertainty in analytical measurements. Ann Clin Biochem 35 371-379. 

In order to define this variety of food matrices, chemical composition differences that primarily influence chemical analytical measurements have to be considered. Major food components determining basic chemical make-up are the proximate composition of fat, protein, carbohydrate, ash, and moisture. Variations in ash content in general have a minor influence on analytical methods for other constituents and impact of moisture content can be controlled. Thus the major components influencing analytical performance are the relative levels of fat, protein, and carbohydrate. 

There is an abundance of references defining and describing the role played by QA, Quality Control (QC) and Total Quality Management (TQM) in a modem commercial analytical laboratory. The role played by reference materials (RMs) and certified reference materials (CRMs) in the pursuit of analytical measurement accuracy is also well documented. 

In this Chapter we highlight the practical considerations that must be understood by all users of RMs and CRMs we look at some of the issues of traceability and make the CRM user aware of the uncertainty budgets that need to be considered with the use of CRMs. No attempt will be made to advise CRM users on the proper use of statistics in the analytical measurement process and no statistical approaches on the establishment of measurement uncertainty will be given. There are a number of good texts on the subject which should be consulted. These are listed in the Further Reading section of the references at the end of this Chapter and include Miller and Miller (1993) and Taylor s work for NIST (Taylor 1985). 

There are a number of prerequisites for properly using CRMs in these tasks, including established quality control of the laboratory s analytical measurement operations and proven statistical control of the analytical measurement process. Publications describing the use of RMs and CRMs are not as plentiful as those on how CRMs are made but, in addition to the ISO/REMCO Guides 30-35, the ISO/REMCO publication The role of reference materials in achieving quality in analytical chemis-try"(ISO 9000 1987), the NIST Handbook for SRM users (Taylor 1995), and the various LGC-VAM publications listed under Further Reading should all be consulted. 

LGC - VAM Publications (i) The Fitness for Purpose of Analytical Methods, A Laboratory Guide to Method Validation and Related Topics, (2) Practical Statistics for the Analytical Scientist A Bench Guide By TJ Farrant, (3) Trace Analysis A structured Approach to Obtaining Reliable Results By E Pritchard, (4) Quantifying Uncertainty in Analytical Measurement, and (5) Quality in the Analytical Chemistry Laboratory. LGC/RSC Publications, London, England. 

Thompson M (1997) Comparability and Traceability in Analytical Measurements and Reference Materials. Analyst 122 1201-1205. 

Within Europe there are thousands of organizations concerned with analytical measurement. However, within the broad field of testing, chemical measurement has generally been poorly represented. EURACHEM was established to address this concern by enabling analytical laboratories to work together, across international boundaries, on analytical measurement issues. EURACHEM s uniqueness as an organization comes from its primary concern, which is the analytical quality of chemical measurement. 

The UK Government has, for more than six years, funded the Valid Analytical Measurement (VAM) Programme, which is aimed at improving the quality and comparability of analytical measurements. The work undertaken within VAM is key to the underpinning of a modern physico-chemical and biochemical National Measurement System, By disseminating the activities of VAM across international boundaries and linking with other national measurement system VAM also aims to ensure the comparability of data worldwide. Thus VAM provides an infrastructure under which reliable measurements can be made for trade, regulation and health and safety provision. 

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