Overview of chromatographic and electrophoretic methods for the determination of branched-chain amino acids

The significance of branched-chain amino acids in diseases was clearly shown over the years. This review aims to describe the available techniques for their analytical determination. The article provides examples of the use of various analytical methods. The methods are divided into two categories: derivatization and non-derivatization approaches. Separation is achieved through different chromatography or capillary electrophoresis techniques and can be combined with different detectors such as flame ionization, ultraviolet, fluorescence, and mass spectrometry. It compares the application of various derivatization reagents or detection as such for different detectors.     

Some practical examples of method validation in the analytical laboratory

Method validation is a key element in both the elaboration of reference methods and the assessment of a laboratory's competence in producing reliable analytical data. Hence, the scope of the term method validation is wide, especially if one bears in mind that there is or at least should be a close relation between validation, calibration and quality control QA/QC. Moreover, validation should include more than the instrumental step only since the whole cycle from sampling to the final analytical result is important in the assessment of the validity of an analytical result. In this article validation is put in the context of the process of producing chemical information. Two cases are presented in more detail: the development of a European standard for chlorophenols and its validation by a full scale collaborative trial, and the intralaboratory validation of a method for ethylenethiourea using alternative analytical techniques.     

Validation of analytical methods involved in dissolution assays: Acceptance limits and decision methodologies

Dissolution tests are key elements to ensure continuing product quality and performance. The ultimate goal of these tests is to assure consistent product quality within a defined set of specification criteria. Validation of an analytical method aimed at assessing the dissolution profile of products or at verifying pharmacopoeias compliance should demonstrate that this analytical method is able to correctly declare two dissolution profiles as similar or drug products as compliant with respect to their specifications. It is essential to ensure that these analytical methods are fit for their purpose. Method validation is aimed at providing this guarantee. However, even in the ICHQ2 guideline there is no information explaining how to decide whether the method under validation is valid for its final purpose or not. Are the entire validation criterion needed to ensure that a Quality Control (QC) analytical method for dissolution test is valid? What acceptance limits should be set on these criteria? How to decide about method's validity? These are the questions that this work aims at answering. Focus is made to comply with the current implementation of the Quality by Design (QbD) principles in the pharmaceutical industry in order to allow to correctly defining the Analytical Target Profile (ATP) of analytical methods involved in dissolution tests. Analytical method validation is then the natural demonstration that the developed methods are fit for their intended purpose and is not any more the inconsiderate checklist validation approach still generally performed to complete the filing required to obtain product marketing authorization.     

Analytical Techniques for Phytocannabinoid Profiling of Cannabis and Cannabis-Based Products—A Comprehensive Review

Cannabis is gaining increasing attention due to the high pharmacological potential and updated legislation authorizing multiple uses. The development of time- and cost-efficient analytical methods is of crucial importance for phytocannabinoid profiling. This review aims to capture the versatility of analytical methods for phytocannabinoid profiling of cannabis and cannabis-based products in the past four decades (1980–2021). The thorough overview of more than 220 scientific papers reporting different analytical techniques for phytocannabinoid profiling points out their respective advantages and drawbacks in terms of their complexity, duration, selectivity, sensitivity and robustness for their specific application, along with the most widely used sample preparation strategies. In particular, chromatographic and spectroscopic methods, are presented and discussed. Acquired knowledge of phytocannabinoid profile became extremely relevant and further enhanced chemotaxonomic classification, cultivation set-ups examination, association of medical and adverse health effects with potency and/or interplay of certain phytocannabinoids and other active constituents, quality control (QC), and stability studies, as well as development and harmonization of global quality standards. Further improvement in phytocannabinoid profiling should be focused on untargeted analysis using orthogonal analytical methods, which, joined with cheminformatics approaches for compound identification and MSLs, would lead to the identification of a multitude of new phytocannabinoids.     

The current state of analytical control in Lithuania

In Lithuania research and development in chemical analysis are concentrated in scientific institutes and universities. The main fields of interest focus on biosensors, electrochemical sensors, sampling techniques and methods, study of atomization processes in spectrochemical analysis and noise evaluation in analytical measurements. Some laboratories also take part in international environmental monitoring programmes. There are about 50 researchers at the Ph.D. level engaged in analytical chemistry and several hundred technicians specialized in the field of analytical control. About one hundred chemical laboratories are active in scientific institutes, universities and factories. Specialized laboratories of chemical analysis are at the disposal of Environmental Control and Health Protection Departments and forensic investigation organizations. So far no laboratories are accredited according to the ISO 9000 norms. Special courses on analytical chemistry are offered at a few schools of higher education in the country. Only at the Department of Analytical Chemistry of the University of Vilnius specialized programmes are available to postgraduate students working towards a Ph.D. to improve their skills in current techniques of analytical chemistry. Recently the Technical Committee TC-16 for Chemical Analysis was formed within the standardization system of Lithuania. Its main activities are centered on issues such as national terminology, certified reference materials (CRMs), analytical methods and analytical quality assurance. There are numerous problems related to national terminology, the preparation of special documents in the field of analytical control and the production of regional environmental CRMs. Problems, also arise in obtaining and using CRMs for analytical instrument calibration and validation.     

药物分析中薄层色谱的方法认证

在药物分析中,针对所要求的性能参数,对一个薄层色谱程序的各个环节必须进行的认证方法和认可标准进行了讨论。建议当提出结果报告时,应附上关于对方法的认证参数和认证方法的说明。     

恶臭成分的仪器分析方法研究进展

对恶臭污染物质的测定内容包括恶臭物质的总体浓度、具体成分及相应的浓度水平。随着痕量气体分析技术水平的提高,增加受控恶臭污染物的种类成为可能。恶臭物质因种类繁多、性质差异大,分析方法多种多样。该文根据不同恶臭物质的物理、化学特性,结合国内外最先进的分析技术和标准,从恶臭物质样品采集、前处理以及不同分析仪器的选择方面,综述了目前恶臭成分的仪器分析方法研究进展。     

Applications of Thermal Analysis and Coupled Techniques in Pharmaceutical Industry

Thermal analysis methods are well-established techniques in research laboratories of pharmaceutical industry. The robustness and sensitivity of instrumentation, the introduction of automation and of reliable software according to the industrial needs widened considerably the areas of applications in the last decade. Calibration of instruments and validation of results follow the state of the art of cGMP as for other analytical techniques. Thermal analysis techniques are especially useful for the study of the behavior of the poly-phasic systems drug substances and excipients and find a unique place for new delivery systems. Since change of temperature and moisture occur by processing and storage, changes of the solid state may have a considerable effect on activity, toxicity and stability of compounds. Current requirements of the International Conference of Harmonisation for the characterization and the quantitation of polymorphism in new entities re-enforce the position of thermal analysis techniques. This challenging task needs the use of complementary methods. Combined techniques and microcalorimetry demonstrate their advantages. This article reviews the current use of thermal analysis and combined techniques in research and development and in production. The advantage of commercially coupled techniques to thermogravimetry is emphasized with some examples. This revised version was published online in August 2006 with corrections to the Cover Date.     

Quantitative Determination of Copper: Combining Project-Based Laboratories with Single-Analyte Detection

A multiweek experiment is presented for use in undergraduate instrumental analysis courses. The experiment combines project-based laboratories and single-analyte detection to provide students with experience in method development and validation, and to give them a more realistic experience in the analytical laboratory. Working together as a team, students develop methods for the detection of an analyte (i.e., copper) in water samples using at least two spectroscopic instruments (e.g., ICP-AES, AA, UV-vis, fluorescence). Student teams are given only topical information about their projects, and must research and plan the analyses, learn the instrumental methods to be used, obtain figures of merit (e.g., detection limits) from Beers law plots, analyze commercial water samples, and produce a standard operating protocol for one of their methods, which will be validated by another team during a subsequent laboratory. Goals of this approach include promoting teamwork and building student confidence in approaching and operating unfamiliar instrumentation. Even more importantly, students are placed in the position of being scientists and having to make decisions and recommendations. Each step of the analytical process must be carefully considered, and its significance assessed as there are no recipes to follow as they develop their methods and make comparisons between different techniques for the determination of a single analyte.     

Chromatographic separation techniques and data handling methods for herbal fingerprints: a review

As herbal medicines have an important position in health care systems worldwide, their current assessment and quality control are a major bottleneck. Over the past decade, major steps were taken not only to improve the quality of the herbal products but also to develop analytical methods ensuring their quality. Nowadays, chromatographic fingerprinting is the generally accepted technique for the assessment and quality control of herbal products. This paper briefly considers the evolution of the regulations and guidelines on the quality control of herbal medicines, and reviews the established analytical techniques for herbal fingerprinting with an emphasis on the most recent developments, such as miniaturized techniques, new stationary phases, analysis at high temperatures and multi-dimensional chromatography. Accessory to the new analytical techniques, the chemometric data handling techniques applied are discussed. Chemometrics provide scientists with useful tools in understanding the huge amounts of data generated by the analytical advances and prove to be valuable for quality control, classification and modelling of, and discrimination between herbal fingerprints.     

Kinetic Methods of Analysis: How Do They Rate?

During the past few years there has been a resurgence of interest in kinetic aspects of analytical chemistry and in kinetic methods of analysis. The increased activity is a result of advances that have been made in instrumentation and in data processing techniques. Still, the kinetic approach is not widely applied by practicing analytical chemists. Why is this true? Why are kinetic methods not among the most common methods in use by analytical chemistry? This paper discusses the advantages and limitations of kinetic methods and addresses the probable reasons that they are not widely used. Several new principles have cmerged that are guiding the development of new kinetic-based determinations. These developments have made it possible to compensate for errors that result from changes in reaction conditions and to determine accurately multiple components in mixtures. With these advances kinetic methods are approaching the reliability of traditional equilibrium-based determinations and should be re-evaluated by analytical chemists.     

Structure analytical methods for quantitative reference applications

The analytical methods mass spectrometry, UV/Vis, IR, Raman, Fluorometry, XRD, Mössbauer, and NMR used to elucidate chemical structure are evaluated regarding their capabilities to be used as primary analytical techniques in quantitative measurements, considering the criteria in the CCQM definition of primary methods. This includes a review of the respective measurement equations, the evaluation of the measurement uncertainty, and a discussion of evidence for the “highest metrological level”, as obtained from intercomparisons in contest with other methods. It is shown that only few methods fulfill the CCQM criteria. Quantitative NMR spectroscopy is one of them and may be considered as a potential primary method as recommended by CCQM because of being free of empirical factors in the uncertainty budget.     

Multisyringe Flow Injection Potentialities for Hyphenation with Different Types of Separation Techniques

The advantages of combining flow techniques with separation techniques are noteworthy. Flow-based methods are excellent tools for automating analytical procedures owing to their speed of analysis, reagent and sample saving ability, versatility, and inexpensive equipment. However, flow-based methods alone do not allow the separation of several analytes in a mixture. On the other hand, separation techniques (viz., chromatographic separations, capillary electrophoresis), widely used in analytical research due to high selectivity, require more expensive instrumentation. Thus, the combination of both techniques achieved the required selectivity with a more versatile, automated and, in some cases, low-cost methodology.

Multisyringe flow injection evidences interesting features with the utilization of the aforementioned combination of methods. Its potential for hyphenation with different separation techniques have been recently explored and are depicted in the present paper.     

Calibration by orthogonal and common least squares — Theoretical and practical aspects

Consequences resulting from a three-dimensional calibration model introduced in [5] are investigated. Accordingly, there exists a different statistical background for the calibration, the analytical evaluation and the validation step. If the errors of the concentration values are not negligible compared with the errors of the measured values, orthogonal calibration models have to be used instead of the common Gaussian least squares (GLS). Four different approximation models of orthogonal least squares, Wald's approximation (WA), Mandel's approximation (MA), Geometrical mean (GM), and Principal component estimation (PC) are investigated and compared with each other and with GLS by simulations and by real analytical applications. From the simulations it can be seen that GLS is affected by bias in the estimates of both slope and intercept in the case of increasing concentration error. On the other hand, the orthogonal models estimate the calibration parameter better. The best fit is obtained by Wald's approximation. It is shown by simulations and real analytical calibration problems that orthogonal calibration has to be used in all cases in which the concentration errors cannot be neglected compared to the errors of the measured values. This is in particular relevant in recovery experiments for validation by means of comparison of methods. In such cases orthogonal least squares methods have always to be applied where the use of WA is recommended. The situation is different in the case of ordinary calibration experiments. The examples considered show small existing differences between the classical GLS and the orthogonal procedures. In doubtful cases both GLS and WA should be computed where the latter should be used if significant differences appear.     

催化剂上积炭结构和组成的分析研究方法

对常用分析研究催化剂上积炭结构和组成的方法,如核磁共振、X射线衍射、红外、拉曼光谱、热分析方法以及紫外可见光谱等现代分析方法的特征和性能进行了综述。指出现代仪器分析方法在考察催化剂积炭行为方面发挥了重要作用,不同方法各具特色,在具体的催化剂表面积炭分析应用中应综合考虑各种方法的优缺点,从而确定最佳表征手段。随着分析仪器的不断发展和完善,仪器分析方法必将在催化剂积炭研究与分析中发挥越来越大的作用。     

Advances in methodology for the validation of methods according to the International Organization for Standardization. Application to the determination of benzoic and sorbic acids in soft drinks by high-performance liquid chromatography

Robust chemometric techniques such as least median of squares regression, H15 Huber estimator and Lenth's method are fundamental tools in the validation of analytical methods since they contribute the strategies needed to estimate efficiently parameters such as robustness, linear range, selectivity, accuracy (trueness and precision) and the capability of detection. In addition, the capability of discrimination defined as a generalisation of the capability of detection for any nominal concentration is evaluated. The new strategy proposed is applied to the validation of a chromatographic method for use in systematic analysis.     

Analysis of recent pharmaceutical regulatory documents on analytical method validation

All analysts face the same situations as method validation is the process of proving that an analytical method is acceptable for its intended purpose. In order to resolve this problem, the analyst refers to regulatory or guidance documents, and therefore the validity of the analytical methods is dependent on the guidance, terminology and methodology, proposed in these documents. It is therefore of prime importance to have clear definitions of the different validation criteria used to assess this validity. It is also necessary to have methodologies in accordance with these definitions and consequently to use statistical methods which are relevant with these definitions, the objective of the validation and the objective of the analytical method. The main purpose of this paper is to outline the inconsistencies between some definitions of the criteria and the experimental procedures proposed to evaluate those criteria in recent documents dedicated to the validation of analytical methods in the pharmaceutical field, together with the risks and problems when trying to cope with contradictory, and sometimes scientifically irrelevant, requirements and definitions.