International comparability of chemical measurement results

The international system of units (SI) is an internationally recognized system based on standards of long-term stability; by the use traceable measurements it provides an international infrastructure for realizing comparable measurements. The work of the Consultative Committee for Amount of Substance (CCQM) and the implementation of the Mutual Recognition Arrangement (MRA) are facilitating an international programme for metrology in chemistry to extend this infrastructure to the field of chemical measurements. The major points of this programme, which include the execution of international comparisons and the construction of a key comparison and calibration database at the BIPM, are described.     

Applications of the Internet to PT

The Internet provides laboratory professionals with a unique opportunity to come together as a network and to develop an integrated system for monitoring the quality of testing in their laboratories on a real-time basis. Once established this network could provide a quality and standards promoting infrastructure for catalyzing the standardization process. Through a collaborative sharing of information on performance and through the use of a common database with harmonized test materials, proficiency testing providers can play a pivotal role in developing such a system. The challenge is now up to us.     

The Italian way: Accreditation and continuous quality improvement in clinical laboratories

 The transition from quality assurance of the analytical phase to the quality management of total testing in clinical laboratories is still at an early stage. But it has begun. Accreditation through voluntary, educational and professional schemes, like the Clinical Pathology Accreditation scheme, is a useful tool for following defined standards of practice and having these independently confirmed on the basis of a peer review. Approved clinical laboratories can obtain a hallmark of performance and offer reassurance to users of their services. However, accreditation does not guarantee an error-free service; it is not the final step, but an important stage in the improvement process. Quality is a journey and continuous quality improvement is the paradigm for better addressing our efforts to satisfy customers' expectations for the desired health outcomes related to a high-quality laboratory service.     

Assessing publically financed metrology expenditure against economic parameters

The objective of this paper is to provide an economic perspective to those involved in public financing of the national metrology infrastructure. Whereas justifications for subsidising the national metrological activities are often historically biased, we raise the importance of economic considerations, which could be used during prioritisation. The expenditure in measurement and metrology infrastructure of European countries are compared to economic indicators for quality of life. Various proxies are used, such as measuring instruments sale (for measurement infrastructure) and data from the BIPM’s KCDB (as a proxy for national standards). As the EU Internal Market also holds for the provision of metrological services, the paper exposes possible trends regarding public financing to the sector.

Genetic algorithms applied to the selection of factors in principal component regression

Using principal component regression (PCR) as a multivariate calibration tool, always brings up the question what subset of factors, i.e. principal components (PCs) gives the best calibration model. Normally factor selection is based on deterministic methods like top–down procedures, forward–backward-stepwise variable selection or correlated principal component regression (CPCR). In contrast to this, we applied a stochastic method, i.e. a genetic algorithm (GA) for factor selection in this paper. A new kind of fitness function was applied which combined the prediction error of the calibration and an independent validation set. The performance of eigenvalue and correlation ranking was compared. A general statistical criterion for judging the significance of differences between individual calibration models is introduced. In this context it could be shown that for the uncertainties of the standard deviations representing the prediction errors a very simple approximation formula holds which only includes the number of standards. For the current applications it is shown that the GA gives a result very close to CPCR-solutions.     

Research Data in Chemistry – Results of the first NFDI4Chem Community Survey

Good research data management (RDM) requires a constant endeavour of the researchers but – first and foremost – user-friendly infrastructure and well accepted standards need to be developed for the researchers. The national research data infrastructure initiative for chemistry in Germany NFDI4Chem sets out to embrace the challenge of creating a general research data management portal and hereby connecting already existing infrastructure as well as to foster the cultural change in chemistry towards digitalization by developing general minimum information standards for all methods used and teaching RDM principles to the community. In order to serve the needs of the chemical community at its best, NFDI4Chem accomplishes regular community surveys. The first survey has been performed in 2019 and the results were condensed into the NFDI4Chem proposal. This article summarizes the design of the study and its results. With regard to the project development, this first national survey serves as zero-point of all upcoming efforts in research data management.     

Evaluating Properties of Green Concrete Produced Using Waste Marble Powder,Quarry Dust,and Paper Pulp

Industrial waste locks are used as raw materials to reduce harmful effects on the environment and improve environmental performance. Marble clay powder can be used as a filling aid and can fill voids in concrete structures. This article will show you how to use a maximum natural sand alternative in concrete with marble powder and quarry dust. The challenge of the 21st century is to change to a new form that can support the natural system. This necessitates a radical rethinking of how to give the community infrastructure and housing. Making a concerted effort to develop novel, innovative, and alternative construction materials may be necessary. Jungles of concrete around cause's impact on the Environment and it would result in climate change. Mankind must avoid the use of things that are detrimental to the environment. So in this paper, it is decided to address the issue by adopting the use of the green concrete concept which is environmentally friendly. Green concrete is concrete made up using industrial wastes such as marble powder, quarry dust, wood ash, paper pulp, etc. Green concrete, which is capable of sustainable development, helps to reduce the consumption of natural resources, energy use, and environmental pollution. Green concrete is more cost-effective than ordinary concrete and reduces the cost of resultant concrete by 14%–20%. It is also observed that the alkali-aggregate reaction and sulfate attack resistance of concrete are both significantly improved. Green concrete is a useful tool for lowering environmental pollution and enhancing concrete's resistance to harsh conditions. All stages of infrastructure construction and rehabilitation will follow this trend of using new cement and techniques. Green concrete's adaptability and its performance derivatives will meet a variety of future needs.     

Applications of LC/ESI-MS/MS and UHPLC/Qq-TOF-MS for the determination of 141 pesticides in tea

This paper presents the applications of LC-electrospray ionization (ESI)/MS/MS and ultra-HPLC (UHPLC)/ESI quadrupole (Qq)-time-of-flight (TOF) MS for the determination of 141 pesticides in tea. Pesticides were extracted and cleaned up from tea with a modified quick, easy, cheap, effective, rugged, and safe method using graphitized carbon black and primary-secondary amine sorbents. Quantification was achieved using matrix-matched standard calibration curves with isotopically labeled standards or a chemical analog as internal standards in an analytical range from 5 to 500 microg/kg. The LC/ESI-MS/MS served as a reliable tool to quantify the pesticides due to its superior sensitivity and good repeatability. Its method performance characteristics that include overall recovery, intermediate precision, and measurement uncertainty were evaluated according to a statistically designed experiment, i.e., a nested design. About 87% of the pesticides had recoveries between 81 and 110%; 94% had an intermediate precision < or = 20%; and 90% showed measurement uncertainty < or = 40%. About 92% of the pesticides were able to be detected at 5 microg/kg with an S/N > or = 3. The UHPLC/Qq-TOF-MS showed much less sensitivity and poorer repeatability compared to the LC/ESI-MS/MS, and, therefore, it was primarily used for confirmatory purposes based on the accurate mass measurement and isotopic patterns.     

Advantages of atmospheric pressure photoionization mass spectrometry in support of drug discovery

The performance of the atmospheric pressure photoionization (APPI) technique was evaluated against five sets of standards and drug-like compounds and compared to atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI). The APPI technique was first used to analyze a set of 86 drug standards with diverse structures and polarities with a 100% detection rate. More detailed studies were then performed for another three sets of both drug standards and proprietary drug candidates. All 60 test compounds in these three sets were detected by APPI with an overall higher ionization efficiency than either APCI or ESI. Most of the non-polar compounds in these three sets were not ionized by APCI or ESI. Analysis of a final set of 201 Wyeth proprietary drug candidates by APPI, APCI and ESI provided an additional comparison of the ionization techniques. The detection rates in positive ion mode were 94% for APPI, 84% for APCI, and 84% for ESI. Combining positive and negative ion mode detection, APPI detected 98% of the compounds, while APCI and ESI detected 91%, respectively. This analysis shows that APPI is a valuable tool for day-to-day usage in a pharmaceutical company setting because it is able to successfully ionize more compounds, with greater structural diversity, than the other two ionization techniques. Consequently, APPI could be considered a more universal ionization method, and therefore has great potential in high-throughput drug discovery especially for open access liquid chromatography/mass spectrometry (LC/MS) applications.     

Pesticides in water and the performance of the liquid-phase microextraction based techniques. A review

The control of pesticides in surface, drinking and groundwater is nowadays a real necessity. In the European Community, their concentration must comply with the established parametric and environmental quality standards (EQSs). Regarding the new legislation, this article updates the information concerning the monitoring of pesticides and the technical specifications for their measurement in water samples where ultra-sensitive analytical methods are required. For some compounds, like pesticides, there is still a need to improve the performance of the existing methods. High sensitive techniques like gas chromatography tandem mass spectrometry (GC–MS/MS) and liquid chromatography coupled with mass spectrometry (LC–MS) have been developed. However, for most of the substances present at trace and ultra-trace levels the extraction and preconcentration steps are so far essential for their detection. Advances at a micro scale have been made and different types of microextractions are being developed. Liquid-phase microextraction (LPME) is an example. The study of this technique has increased in the last years and some innovations have been recently reported for pesticides water analysis. This article reviews the new developed LPME-based techniques and compares its performance with the analytical specifications established for pesticides water monitoring. The results show that LPME-based techniques can be a promising tool to improve the nowadays performance of methods used in pesticides water control.     

Practical quantitative biomedical applications of MALDI-TOF mass spectrometry

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) is used to obtain fast and accurate determinations of molecular mass, but quantitative determinations are generally made by other techniques. In this study we illustrate the practical utility of automated MALDI-TOFMS as a tool for quantifying a diverse array of biomolecules covering an extensive molecular weight range, and present in biological extracts and fluids. Growth hormone was measured in rat pituitary tissue; insulin in human pancreatic tissue; homovanillic acid in human urine; and LVV-hemorphin-7, epinephrine and norepinephrine in human adrenal and pheochromocytoma tissues. Internal standards including compounds of similar molecular weight, structural analogs or isotopomers were incorporated into each analysis. We report on the current practical limitations of quantitative MALDI-TOFMS and highlight some of the potential benefits of this technique as a quantitative tool.     

Use of high-performance thin layer chromatography by the American Herbal Pharmacopoeia

TLC characterizations are among the key identity tests in most pharmacopoeial monographs. Pharmacopoeial standards are typically used by industry as a basis for meeting QC requirements and current good manufacturing practices (cGMPs). TLC is a relatively low-cost, highly versatile tool for developing specifications for raw materials, as well as for the various preparations for which pharmacopoeial standards are created. In addition to its use in the development of identity tests, TLC is a valuable tool for screening plant samples that pharmacopoeias must review in the development of monographs and botanical reference materials (BRMs). Specifically, HPTLC is the ideal TLC technique for these purposes because of its increased accuracy, reproducibility, and ability to document the results, compared with standard TLC. Because of this, HPTLC technologies are also the most appropriate TLC technique for conformity with GMPs. This article highlights the manner in which HPTLC is used by the American Herbal Pharmacopoeia (AHP) in the development of AHP monograph identity standards, the identification of adulterating species, and the development of AHP-verified BRMs.     

A fast high throughput method for the determination of acidity constants by capillary electrophoresis. 3. Basic internal standards

A set of 25 monoprotic bases is proposed as internal standards for pK(a) determination by capillary electrophoresis. The pK(a) of the bases is determined and compared with available literature data. The capillary electrophoresis internal standard method offers numerous advantages over other typical methods for pK(a) determination, especially of analysis time and buffer preparation. However, it requires disposing of appropriate standards with reference pK(a) value. The set of bases established in this work together with the set of acids previously established provide a reference set of compounds with well-determined acidity constants that facilitate the process of selecting appropriate internal standards for fast pK(a) determination by capillary electrophoresis in high throughput screening of pharmaceutical drugs. In addition, the performance of the method when acidic internal standards are used for the determination of acidity constants of basic internal standards has also been tested. Although higher errors may be expected in this case, good agreement is observed between determined and literature values. These results indicate that in most cases structural similarity between the analyte and the internal standard might not be an essential requirement in the internal standard method.     

Towards compound-independent calibration for organic compounds using online isotope dilution mass spectrometry

Isotope dilution mass spectrometry (IDMS) can be considered a primary measurement method directly traceable to the International System of Units (SI). This measurement technique is increasingly employed in routine laboratories, owing to its unequalled analytical performance, precision and ease of accreditation. Unfortunately, for the adequate application of IDMS, several isotopically labelled standards, corresponding to the compounds of interest, are required. Additionally, when the enriched isotope is continuously added after a chromatographic separation, and an elemental ion source is used, it allows quantification of the different analytes being eluted from the column without requiring specific standards for each compound (online IDMS). In this article, we discuss how the traditional applicability of online IDMS for elemental speciation can be dramatically expanded by using carbon isotope tracers, oxidation or combustion reactions and a conventional molecular ion source. With such a strategy every carbon-containing compound being eluted from a chromatography system can be quantified without the need for specific standards as long as quantitative combustion/oxidation and complete elution occur. So far, only gas chromatography–combustion–mass spectrometry applications have been described, but recent results indicate the great possibilities of extending this novel approach to the quantification of organic compounds after separation by liquid chromatography.     

Theory and application of dissociative electron capture in molecular identification

The coupling of an electron monochromator (EM) to a mass spectrometer (MS) has created a new analytical technique, EM-MS, for the investigation of electrophilic compounds. This method provides a powerful tool for molecular identification of compounds contained in complex matrices, such as environmental samples. In particular, EM-MS has been applied to the detection of nitrated aromatic compounds, many of which are potent mutagens and/or carcinogens and are considered environmental hazards. EM-MS expands the application and selectivity of traditional MS through the inclusion of a new dimension in the space of molecular characteristics-the electron resonance energy spectrum. EM-MS also enhances detection sensitivity as well because the entire electron flux of the proper energy can be delivered into the negative ion resonance that is analytically most useful to solving the problem at hand. However, before this tool can realize its full potential, it will be necessary to create a library of resonance energy scans from standards of the molecules for which EM-MS offers a practical means of detection. Unfortunately, the number of such standards is very large and not all of the compounds are commercially available, making this library difficult to construct. Here, an approach supplementing direct measurement with chemical inference and quantum scattering theory is presented to demonstrate the feasibility of directly calculating resonance energy spectra. This approach makes use of the symmetry of the transition-matrix element of the captured electron to discriminate between the spectra of isomers. As a way of validating this approach, the resonance values for 25 nitrated aromatic compounds were measured along with their relative abundance. Subsequently, the spectra for the isomers of nitrotoluene were shown to be consistent with the symmetry-based model. The initial success of this treatment suggests that it might be possible to predict negative ion resonances and thus create a library of EM-MS standards.     

Analytical tools for monitoring changes in physical and chemical properties of chromatography resin upon reuse

Protein A resins are often reused for multiple cycles to improve process economy during mAb purification. Significant reduction in binding capacity and product recovery are typically observed due to the presence of unwanted materials (foulants) deposited on the resin upon reuse. In this paper, we have used a wide spectrum of qualitative and quantitative analytical tools (particle size analysis, HPLC, fluorescence, SEM, MS, and FTIR) to compare the strengths and shortcomings of different analytical tools in terms of their capability to detect the fouling of the resin and relate it to chromatographic cycle performance. While each tool offers an insight into this complex phenomena, fluorescence is the only one that can be used for real‐time monitoring of resin fouling. A correlation could be established between fluorescence intensity and the process performance attributes (like yield or binding capacity) impacted upon resin reuse. This demonstration of the application of fluorescence for real‐time monitoring correlated empirically with process performance attributes and the results support its use as a PAT tool as part of a process control strategy. While the focus of this paper is on fouling of protein A chromatography resin, the approach and strategy are pertinent to other modes of chromatography as well.     

Quantitative determination of compounds in mixtures by B2E=constant linked scans

The B²E = constant linked scan is shown to be an excellent tool for quantifications with reversed geometry mass spectrometers. Deuterium-labelled analogues may be used as internal standards, thus providing very simple clean-up procedures. The principle is demonstrated with the example of chloro-substituted benzoic acid methyl esters. Possible interferences arising from isotope peaks are discussed. The method is applied to the quantification of caffeine in beverages.     

Thermal diesel-like analysis

Biofuel has been obtained by cracking of soybean (Glycine sp.) oil, which is characterized by acidity index, density, cetane index, copper corrosion, carbon residue, fulgor point, and heat of combustion. In order to evaluate the quality of biofuel as well as detect its adulteration with vegetable oil, partial least squares regression calibration models based on thermogravimetric (TG) analysis were used as a precise and an accurate method. Thirty mixtures of biofuel/diesel/vegetable oil standards were prepared. Twenty of them were used for calibration, and ten for validation. The results have shown that the thermogravimetric analysis, PLS/TG, presented the best performance for the detection of vegetable oil contamination with a root mean square error of prediction (RMSEC% w/w) of 0.23, with a relative error of prediction of 3.6%, corroborating with the success of TG analysis application to determine the quality of biofuels and diesel/biofuel blends, showing that the TG analysis is an excellent tool to control quality of biofuels.     

The detection of nitrated tyrosine in neuropeptides: a MALDI matrix-dependent response

Neuropeptides are a diverse class of signaling molecules that typically have one or more posttranslational modifications. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is an effective tool for identification and characterization of neuropeptides from samples as small as individual neurons. However, the detection of one particular posttranslational modification—nitrotyrosine—has been problematic because of the lability of the nitro group of nitrotyrosine under MALDI-MS conditions. The detection of nitrated tyrosine in peptide standards was dependent on the MALDI matrix used for the analysis. Specifically, sinapinic acid was the optimum matrix tested to observe this modification while it was not consistently detected with matrices such as 2,5-dihydroxybenzoic acid. Using the optimized procedures, several identified nitric-oxide-synthase positive neurons from Lymnaea stagnalis were tested to determine if the neuropeptides present were nitrated. In all cases, the nitrated form of the neuropeptide was not observed. The dependence on the sample-preparation procedures of observing this particular chemical modification demonstrates the need for careful selection of sample-preparation methods with MALDI or the use of other ionization methods.     

Novel approaches in analysis of Fusarium mycotoxins in cereals employing ultra performance liquid chromatography coupled with high resolution mass spectrometry

Rapid, simple and cost-effective analytical methods with performance characteristics matching regulatory requirements are needed for effective control of occurrence of Fusarium toxins in cereals and cereal-based products to which they might be transferred during processing. Within this study, two alternative approaches enabling retrospective data analysis and identification of unknown signals in sample extracts have been implemented and validated for determination of 11 major Fusarium toxins. In both cases, ultra-high performance liquid chromatography (U-HPLC) coupled with high resolution mass spectrometry (HR MS) was employed. ¹³C isotopically labeled surrogates as well as matrix-matched standards were employed for quantification. As far as time of flight mass analyzer (TOF-MS) was a detection tool, the use of modified QuEChERS (quick easy cheap effective rugged and safe) sample preparation procedure, widely employed in multi-pesticides residue analysis, was shown as an optimal approach to obtain low detection limits. The second challenging alternative, enabling direct analysis of crude extract, was the use of mass analyzer based on Orbitrap technology. In addition to demonstration of full compliance of the new methods with Commission Regulation (EC) No. 401/2006, also their potential to be used for confirmatory purposes according to Commission Decision 2002/657/EC has been critically assessed.