Using new structurally related additive schemes in the precalculation of gas chromatographic retention indices of polychlorinated hydroxybiphenyls on HP-5 stationary phase

A new additive scheme is proposed for the precalculation of gas chromatographic retention indices of complex organic compounds. The principal feature of this approach is the absence of previously calculated I increments for any structural fragments or functional groups in the molecule. Instead, arithmetical operations involving I values of simpler structural analogues of target compounds are used directly. I precalculation for polychlorinated hydroxybiphenyls (839 congeners) on the HP-5 stationary phase was chosen as one of the most important applications of the method under discussion. Such a large number of congeners cannot be obtained as reference samples and their gas chromatographic (GC)-mass spectrometric (MS) identification should therefore be based currently on precalculated I values.     

The assessment of compliance with legal limits. Part 2. How to consider both type I and type II errors when working in the concentration domain

Considering the uncertainty of measurement when assessing compliance with reference values given in compositional specifications and statutory limits is still a controversial matter. In theory, assessing compliance requires considering both type I (false positive) and type II (false negative) errors. The more the concentration of the analyte in the sample under investigation is close to the allowed concentration limit, the more critical it is to consider both types of errors. This paper describes how this could be done. The matter is discussed in the light of the most recent literature information.     

Correlation of antioxidant depletion and mechanical performance during thermal degradation of an HTPB elastomer

Thermal degradation studies of a stabilized HTPB based elastomer were conducted at temperatures from 50 °C to 110 °C. The concentration of extractable antioxidant (AO2246) in the polymer was quantified via AO extraction and a gas chromatography-based method using internal standards. The decrease in extractable AO levels as a function of time and temperature was evaluated and correlated with mechanical property changes. Most importantly, AO depletion features were found to be temperature dependent. At elevated temperatures (>80 °C) extractable AO levels decreased rapidly and faster than the concurrent loss in mechanical properties. While extractable AO concentrations decrease quickly, the material is able to maintain some useful mechanical properties, perhaps via non-extractable or grafted AO species formed during degradation providing additional protection. At lower aging temperatures extractable or free AO levels decreased more slowly than the mechanical properties. Therefore, for condition monitoring purposes a universal correlation between AO levels and aging state or material condition could not be established. Most importantly, however, loss of mechanical properties and oxidative degradation is observed at lower temperatures despite significant levels of free antioxidant in the material. The antioxidant appears to be limited in its effectiveness to completely prevent degradation reactions, or only fractions of the total AO available are actually involved in the inhibition process.     

Monitoring multi-class pesticide residues in fresh fruits and vegetables by liquid chromatography with tandem mass spectrometry

A new analytical method was developed using liquid chromatography with tandem mass spectrometry for the routine analysis of 31 multi-class pesticide residues and applied to approximately 50 fresh fruit and vegetable samples (green bean, cucumber, pepper, tomato, eggplant, watermelon, melon and zucchini). Extraction of the pesticides with ethyl acetate was carried out. The optimal ionisation conditions were selected for each pesticide in the same run. The procedure was validated and the values of some merit figures, such as recovery, precision, linear range, detection limit and quantification limit for each pesticide were calculated together with its calculated expanded uncertainty (U). The average recoveries in cucumber obtained for each pesticide ranged between 74 and 105% at two different fortification levels (n = 10 each) that ranged between 9 and 250 ng g(-1) (depending on the pesticide). The uncertainty associated to the analytical method was lower than 23% for all compounds tested. The calculated limits of detection and quantitation were typically <1 ng g(-1) that were much lower than the maximum residue levels established by European legislation.     

Computer-assisted choice of discrete spacers for anionic isotachophoresis separations

In isotachophoresis (ITP), the sample constituents migrate, depending on their concentrations in the loaded sample, either in fully developed zones or in the boundary layers between the zones of constituents of the corresponding effective mobilities. The latter (spike) migration mode is analytically beneficial in selective detections of trace analytes, especially, when appropriately chosen discrete spacers minimize detection interferences due to matrix constituents. To facilitate a search for suitable mixtures of discrete spacers, a two-step calculation procedure was developed in this work. Using a pool of discrete spacers consisting of 42 anionic and zwitterionic constituents, this procedure was shown effective in the anionic ITP separations performed at pH = 6.5-10.0. Besides the predictions of the migration orders, it was helpful in identifying the spacing constituents that could cause resolution problems due to an uncertainty with which pH of the leading electrolyte solution is known. The ionic mobility and pKa data, taken for the spacing constituents from the literature and the ones obtained from the ITP experiments carried out in this work, were used in the calculations performed in a context with the choice of spacers. Although the data obtained from the ITP experiments provided better results, small uncertainties with which they were acquired (attributable to fluctuations in the experimental conditions) set practical limits in the calculation based choice of multi-component mixtures of the spacing constituents.     

Uncertainty assessment from robustness testing applied on an LC assay for R-timolol and other related substances in S-timolol maleate

The robustness testing of a normal-phase liquid chromatographic (LC) method for the determination of R-timolol and other related substances in S-timolol maleate was performed applying a two-level Plackett-Burman design. Two qualitative and five quantitative factors were examined. Two types of responses were considered, qualitative, i.e. chromatographic performance criteria, and quantitative ones. The latter were taken into account to determine if the analytical procedure was robust. The quantitative responses were the contents of R-timolol in two S-timolol maleate samples. Even though some significant factor effects were observed on the qualitative responses, the R-timolol contents were not significantly different from those observed at nominal conditions, which demonstrated the robustness of the procedure.Since the experiments of the Plackett-Burman design can be assimilated to laboratories in an interlaboratory study, uncertainty can be evaluated using the robustness test data. The robustness test was set-up in such a way that the required variances could be estimated. It was shown that the robustness set-up allows estimating the reproducibility uncertainty without performing an interlaboratory study.     

Improving (Q)SAR predictions by examining bias in the selection of compounds for experimental testing

ABSTRACT

Existing data on structures and biological activities are limited and distributed unevenly across distinct molecular targets and chemical compounds. The question arises if these data represent an unbiased sample of the general population of chemical-biological interactions. To answer this question, we analyzed ChEMBL data for 87,583 molecules tested against 919 protein targets using supervised and unsupervised approaches. Hierarchical clustering of the Murcko frameworks generated using Chemistry Development Toolkit showed that the available data form a big diffuse cloud without apparent structure. In contrast hereto, PASS-based classifiers allowed prediction whether the compound had been tested against the particular molecular target, despite whether it was active or not. Thus, one may conclude that the selection of chemical compounds for testing against specific targets is biased, probably due to the influence of prior knowledge. We assessed the possibility to improve (Q)SAR predictions using this fact: PASS prediction of the interaction with the particular target for compounds predicted as tested against the target has significantly higher accuracy than for those predicted as untested (average ROC AUC are about 0.87 and 0.75, respectively). Thus, considering the existing bias in the data of the training set may increase the performance of virtual screening.     

Towards a new edition of the “Guide to the expression of uncertainty in measurement”

The “Guide to the expression of uncertainty in measurement” (GUM) is an extremely important document. It unifies methods for calculating measurement uncertainty and enables the consistent interpretation and comparison of measurement results, regardless of who obtained these measurements and where they were obtained. Since the document was published in 1995, it has been realised that its recommendations do not properly address an important class of measurements, namely, non-linear indirect measurements. This drawback prompted the initiation of the revision of the GUM in the Working Group 1 of the Joint Committee for Guides in Metrology, which commenced in October 2006. The upcoming revision of the GUM provides the metrological community with an opportunity to improve this important document, in particular, to reflect developments in metrology that have occurred since the first GUM publication in 1995. Thus, a discussion of the directions for this revision is important and timely. By identifying several shortcomings of the GUM and proposing directions for its improvement, we hope this article will contribute to this discussion. Papers published in this section do not necessarily reflect the opinion of the Editors, the Editorial Board and the Publisher.     

Development of a method for estimating an accurate equivalence point in nickel titration of cyanide ions

In a nickel titration of cyanide ions using murexide as indicator, an accurate equivalence point was determined by a non-linear least-squares curve-fitting for a titration curve. This method was developed to establish a standard solution for cyanide ions. In a curve-fitting procedure, a theoretical titration curve was calculated, assuming that nickel ion formed only a 1:4 Ni²⁺:CN⁻ complex with cyanide ions and formed only a 1:1 complex with murexide. Results of the curve-fitting were reasonable at any pH and any indicator concentration studied. The combined standard uncertainty for a concentration of a 1000 mg kg⁻¹ cyanide solution by this method was 0.079%.