The uncertainty of the chemical sample preparation is part of the uncertainty of the measurement result

Accreditation and Quality Assurance -     

The position of the analyst as expert: Yesterday and today

The interrelation between law and analytical chemistry 150 years ago is outlined, showing that similar problems to today already existed at that time. Examples of present-day cases of judicial investigations are given and consequences for the duty of the analytical chemist are discussed. Received: 19 April 2000 / Accepted: 14 June 2000     

The position of the analyst as expert: yesterday and today

The interrelation between law and analytical chemistry 150 years ago is outlined, showing that similar problems to today already existed at that time. Examples of present-day cases of judicial investigations are given and consequences for the duty of the analytical chemist are discussed.     

The application of the measurement uncertainty concept to in-process control in pharmaceutical development

 Any analytical data is used to provide information about a sample. The "possible error" of the measurement can be of extreme importance in order to have complete information. The measurement uncertainty concept is a way to achieve quantitative information about this "possible error" using an estimation procedure. On the basis of the analytical result, the chemist makes a decision on the next step of the development process. If the uncertainty is unknown, the information is not complete; therefore this decision might be impossible. The major problem for the in-process control (IPC) procedure is that not only the repeatability but also the intermediate precision (which expresses the variations within laboratories related to different days, different analysts, different equipment, etc.) has to be good enough to make a decision. Unfortunately, the statistical information achieved from one single analytical run only gives information about the repeatability. This paper shows that the estimation of the measurement uncertainty for IPC is a way to solve the problem and gives the necessary information about the quality of the procedure. An example demonstrates that an estimate of uncertainty based on the standard deviations of an analytical method gives a value similar to one based on the standard deviations obtained from a control chart. Therefore, the estimation is both a very useful and also a very cost-effective tool. Though measurement uncertainty cannot replace validation in general, it is a viable alternative to validation for all methods that will never be used routinely. Received: 24 May 1996 Accepted: 10 August 1996     

Elemental carbon in the atmosphere: challenges for the trace analyst

Summary Elemental carbon is an ubiquitous part of the atmospheric aerosol, originating from all combustion processes. It influences the radiative transfer by its absorbing properties leading to influences on regional climate. While its importance in air chemistry seems to be small there may exist hygienic aspects due to absorbed mutagenic and cancerogenic substances which are not understood completely yet. Soot has unique properties as a tracer for atmospheric transport processes. The mostly hydrophobic character of soot particles influences its life time because it impedes an incorporation into clouds and thus a rapid removal by wet deposition processes. From a literature review a number of tasks for the analyst are formulated concerning improvement of analytical measurement techniques, understanding the change of the surface properties from hydrophobic to hydrophilic, and the use of absorbed substances for source identification which is of importance for a better use of soot as a tracer for atmospheric transport processes.     

From total allowable error via metrological traceability to uncertainty of measurement of the unbiased result

The concept of "total allowable error", investigated by Westgard and co-workers over a quarter of a century for use in laboratory medicine, comprises bias as well as random elements. Yet, to minimize diagnostic misclassifications, it is necessary to have spatio-temporal comparability of results. This requires trueness obtained through metrological traceability based on a calibration hierarchy. Hereby, the result is associated with a final uncertainty of measurement purged of known biases of procedure and laboratory. The sources of bias are discussed and the importance of commutability of calibrators and analytical specificity of the measurement procedure is stressed. The practicability of traceability to various levels and the advantages of the GUM approach for estimating uncertainty are shown.     

A model of the chemical bond must be rooted in quantum mechanics, provide insight, and possess predictive power

In this response to the preceding paper by Bader, we show that the core arguments and statements presented in the latter are flawed. We argue that it is insufficient for a model of the chemical bond to be rooted in quantum mechanics. A good model must in addition provide insight and possess predictive power. Our molecular orbital (MO) model of the chemical bond, in particular, the associated energy-decomposition approach satisfies all these conditions. On the other hand, Atoms-in-Molecules (AIM) theory is only rooted in quantum mechanics as far as its mathematical framework is concerned. The physical status of its central concepts is not so clear. In particular, "bond paths" and "bond critical points" are once more confirmed not to be indicators of a stabilizing interaction. Moreover, AIM theory lacks any predictive power. We also address specific questions raised in the preceding paper. Finally, interpreting chemical bonding implies choosing a perspective on this phenomenon. That there are many perspectives is a matter of fact and this is in no way unphysical. What is unscientific is to claim uniqueness and truth for one of these choices, namely AIM, and to dismiss on this ground all other approaches.     

Mass spectrometric measurement of changes in protein hydrogen exchange rates that result from point mutations

Point mutations, as well as additions or deletions of entire domains, are frequently produced to study protein function; however, to infer function from mutant proteins, it is imperative that their structural integrity be verified. Although detailed structural studies can be performed by using NMR or crystallography, for practical reasons mutant proteins usually are characterized by using less rigorous techniques. Here it is shown that measurement of hydrogen exchange rates via electrospray ionization mass spectrometry is a sensitive and generally applicable method for detection of conformational or dynamic changes that result from point mutations. Hydrogen exchange experiments were performed on a bacterial phosphocarrier protein (HPr) and two variants produced by conversion of either serine-46 to aspartic acid (S46D) or serine-31 to alanine (S31A), where the differences in the ΔG of folding relative to the wild type were 1.5 and 0.5 kcal/mol, respectively. Whereas no significant differences were found for the intact mutant and wild-type proteins, changes in deuterium incorporation could be detected within specific regions produced by peptic proteolysis of the deuterium-labeled proteins. Thus, energetically small changes in conformation (or dynamics) that result from point mutations can be characterized by mass spectrometric measurements of hydrogen exchange rates. Furthermore, these changes can be localized to specific regions within the protein.     

“Quality of a measurement result” is established by means of metrological criteria

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The use of differential photoionization cross sections as a function of excitation energy in assigning photoelectron spectra

A criterion for spectral assignments employing the variation in the differential photoionization cross section as a function of the incident photon energy is described. The He I and He II photoelectron spectra of N₂, CO, CH₃SH, ClHCCHCH₃, H₂CCBrCH₃, and transClHCCHCl are presented and discussed in terms of this criterion.