Counterfeit drugs: analytical techniques for their identification

In recent years, the number of counterfeit drugs has increased dramatically, including not only “lifestyle” products but also vital medicines. Besides the threat to public health, the financial and reputational damage to pharmaceutical companies is substantial. The lack of robust information on the prevalence of fake drugs is an obstacle in the fight against drug counterfeiting. It is generally accepted that approximately 10% of drugs worldwide could be counterfeit, but it is also well known that this number covers very different situations depending on the country, the places where the drugs are purchased, and the definition of what constitutes a counterfeit drug. The chemical analysis of drugs suspected to be fake is a crucial step as counterfeiters are becoming increasingly sophisticated, rendering visual inspection insufficient to distinguish the genuine products from the counterfeit ones. This article critically reviews the recent analytical methods employed to control the quality of drug formulations, using as an example artemisinin derivatives, medicines particularly targeted by counterfeiters. Indeed, a broad panel of techniques have been reported for their analysis, ranging from simple and cheap in-field ones (colorimetry and thin-layer chromatography) to more advanced laboratory methods (mass spectrometry, nuclear magnetic resonance, and vibrational spectroscopies) through chromatographic methods, which remain the most widely used. The conclusion section of the article highlights the questions to be posed before selecting the most appropriate analytical approach.     

中药分析新思路及其质量控制

随着国家对中药现代化的重视,为了更好地诠释中药药性的本质,研究者从不同角度对中药进行研究。分析化学、药学、生物学等多学科的多种不同的技术在这里融合,一些新的思路和方法正在不断涌现,中药的分析与质量控制正沿着综合且全面的方向在不断地发展和前进。该文对当前中药分析新思路及其质量控制进行了简要评述,在此基础上,对中药质量控制的色谱指纹图谱进行了分类说明与研究,表明采用现代分析手段,可以实现对中药质量的有效控制。     

How to remove barriers to medicines trade in emerging economies: the role of medicines regulatory authority in Serbia

The primary role of European pharmaceutical legislation is to safeguard public health while encouraging the development of the pharmaceutical industry, creation of single market for pharmaceuticals with removed barriers to medicines trade. This article presents some important characteristics of pharmaceutical legislation in Serbia, the potential EU candidate country, and the latest improvements of existing national pharmaceutical legislation. Additional explanation is given for the Serbian negotiations with World Trade Organization and measures taken for the harmonisation with Agreements on Technical barriers to Trade (TBT), especially with Agreement on Trade-Related Intellectual Property Rights. Current status of Serbian pharmaceutical market is described, with the highlight of domestic manufacturers??capacity to comply with European Union requirements. National medicines agency is described in the framework of European medicines quality infrastructure. The role and responsibility of national medicines authority to assure access to quality, safe and efficacious medicines on Serbian market is described. The special emphasis is given to agency’s role in harmonisation process, in terms of removing unnecessary barriers to medicines trade in Serbia.     

Rapid identification of cervus antlers by species-specific PCR assay

Abstract

A rapid PCR technology was developed to differentiate Cervus antlers species and adulteration based on the difference in mitochondrial genome. Three specifically designed primer sets were confirmed to have high inter-species specificity and good intra-species stability. Limits of detection were estimated to be 1?ng of genomes for reindeer and 10?ng for the other species. Especially, when the mixture of Cervus antlers and reindeer or sambar was assayed, these primer sets still exhibited strong capability of differentiation but not the conventional COI barcoding. By using the newly developed approach, five batches out of fourteen commercial Cervus antler products were identified to be fake products made from reindeer antlers. It has shown its good potential to be extensively applied in the identification of counterfeits or adulterates of Cornu Chinese medicines for their pulverized and processed form, and even the traditional Chinese patent medicines composed of these species.     

Assessment of hand-held Raman instrumentation for in situ screening for potentially counterfeit artesunate antimalarial tablets by FT-Raman spectroscopy and direct ionization mass spectrometry

Pharmaceutical counterfeiting has become a significant public health problem worldwide and new, rapid, user-friendly, reliable and inexpensive methods for drug quality screening are needed. This work illustrates the chemical characterization of genuine and fake artesunate antimalarial tablets by portable Raman spectroscopy and validation by FT-Raman spectroscopy and ambient mass spectrometry. The applicability of a compact and robust portable Raman spectrometer (TruScan™) for the in situ chemical identification of counterfeit tablets is reported.     

天然化合物芦丁的治疗潜力

芦丁属于类黄酮化合物,广泛存在于人们日常食用的各种蔬菜、水果和中草药中。 芦丁是天然的抗氧化剂,有清除自由基的特性,可调节众多疾病有关的细胞内和细胞外信号通路,影响细胞的生长,分化及其功能,对人们的健康,防病治病起着重要作用。芦丁具有广泛的药理活性,抗氧化、抗炎、抗病毒、抗癌、预防和治疗心脑血管疾病。以芦丁为原料的药品有多种,使用芦丁毒副作用小,安全,成本低。由于芦丁的生物利用度低,在临床上应用受到一定的限制。克服芦丁溶解性差的问题已经有各种方法,例如使用环糊精的络合,磷脂等,改善水溶性,从而增加生物利用度。本文综述了芦丁的多种潜在用途和治疗作用的信息,与药物输送相关的问题,以及改善药物生物利用度的可能方法。重点介绍了芦丁的抗炎、抗癌、降糖、对心血管的保护作用,为天然化合物的开发和利用奠定基础。     

Liquid chromatographic separation of alkaloids in herbal medicines: Current status and perspectives

Alkaloids are a widespread group of basic compounds in herbal medicines and have attracted great interest due to various pharmaceutical activities and desirable druggability. Their distinctive structures make chromatographic separation fairly difficult. Peak tailing, poor resolution, and inferior column‐to‐column reproducibility are common obstacles to overcome. In order to provide a valuable reference, the methodologies and/or strategies on liquid chromatographic separation of alkaloids in herbal medicines proposed from 2012 to 2019 are thoroughly summarized.     

Field-induced wooden-tip electrospray ionization mass spectrometry for high-throughput analysis of herbal medicines

This study demonstrates the first application of field-induced wooden-tip electrospray ionization (ESI) mass spectrometry (MS) for high-throughput analysis of herbal medicines. By application of an opposite and sample-contactless high voltage on the MS inlet rather than wooden tips, a high-throughput analysis device is easily set up, and a relatively fast analysis speed of 6 s per sample was successfully achieved. In addition, fast polarity switching between positive and negative ion detection mode is readily accomplished, which provides more complete chemical information for quality assessment and control of herbal medicines. By using the proposed method, various active ingredients present in different herbal medicines were rapidly detected, and the obtained mass spectra were served as the samples' fingerprints for tracing the origins, establishing the authenticity, and assessing the quality consistency and stability of herbal medicines. Our experimental results demonstrated that field-induced wooden-tip ESI-MS is a desirable method for high-throughput analysis of herbal medicines, with promising prospects for rapidly differentiating the origin, determining the authenticity, and assessing the overall quality of pharmaceuticals.     

Daniel Sennert,The Philosophical Hen,and The Epistolary Quest for a (Nearly-)Universal Medicine

This article explores the Wittenberg Professor Daniel Sennert's (1572–1637) pursuit of nearly universal medicines made from noble metals, which he described in his published works and in private correspondence with his brother-in-law, Michael Döring. Of the medicaments that Sennert sought, one called the Philosophical Hen was especially interesting, and involved feeding a hen silver or gold during propitious astrological conjunctions. Sennert's support of this experiment was rooted in his obsession with experience and can be partially explained by looking to an extensive tradition of natural philosophy and natural history. Sennert explained such nearlyuniversal medicines according to the rational principles of academic medicine, arguing that they strengthened the body's innate heat or acted as universal purgatives. From Sennert's candid epistles, we receive a more historicised portrait of the collaborative experimental process by which chymical medicines were conceptualised and tested, and how the consequences of experimental failure and perceived credulity could be increased scepticism.     

Separation and identification of synthetic dysstuffs by thin-layer electrophoresis and its application in the forensic analysis of liquors

Summary The excessive demand for alcoholic drinks has resulted in the preparation of fakes and created a problem for their identification. Dyestuffs have been added to alcoholic liquors and the separation of these dyestuff mixtures into their various components has been the subject of study by thin-layer electrophoretic techniques on silica gel-G plantes. 10 dyestuffs commonly used in liquors and beverages have been resolved into their components. The migration distances of the separated coloured zones in five electrolytes, either basic or acidic, have been recorded. The technique was found to be particularly suitable for distinguishing fake samples from genuine ones.     

Chromatographic fingerprinting and metabolomics for quality control of TCM

Chromatographic fingerprinting technique of traditional Chinese medicine (TCM) has proved to be a comprehensive strategy for assessing the intact quality of herbal medicine. In general, one could use the chromatographic techniques to obtain a relatively complete picture of herbal medicines, which are in common called chromatographic fingerprints of herbal medicines to represent the so-called phytoequivalence. Based on this, the features of chromatographic fingerprints of herbal medicines have been discussed in some detail. The technique based on chromatographic fingerprinting is essentially a kind of high-throughput and integral tools to explore the complexity of herbal medicines. In order to further control the comprehensive quality of TCMs, some new strategies are proposed to trace the chemical changes of chromatographic fingerprints both in product processing and/or after their administration by modern chromatographic techniques and chemometrics. Combined with metabolomics, it seems possible for one to reveal the working mechanism of TCMs and to further control their intrinsic quality. Finally, the intensive study of chromatographic fingerprinting coupled with multivariate analysis tools developed in bioinformatics and chemometrics are emphasized in order to achieve the aim to reveal the working mechanisms of TCMs and to further control and strengthen TCMs' intrinsic quality in a comprehensive manner.     

Chemometrics and food chemistry: data validation

Chemometrics has often been applied in food chemistry to cluster and classify samples or to produce models for food quality. In recent years, data on food composition have become important for public health protection and food trades. The quality of the available chemical information on foods is a problem; data obtained with the newer analytical methods is scarce and general knowledge about food composition is poor, judged by published tables on food composition. Moreover, agreement between results obtained by different analytical methods is very poor. To overcome this critical problem, several countries have decided to create data banks on food composition. The analytical results to be stored must be validated. Chemometric modelling is useful for this purpose. Interlaboratory studies allow standardization of methods and the preparation of food reference materials. The classical computation of repeatability and reproducibility does not extract all the available information so that a multivariate approach is necessary to improve the quality of a data bank on food composition.     

能量色散-X射线荧光光谱测定中草药痕量镉、铅、铜

为寻求一种能够直接对中草药中重金属进行快速检测的方法,采用压片法对样品进行前处理,建立了能量色散-X射线荧光光谱法快速检测中草药中痕量重金属镉、铅、铜元素的方法。在20 min即可完成检测,镉、铅、铜检出限分别为0.072、0.207、0.340 mg/kg,测试结果表明与原子吸收和ICP-MS相比,本方法数据稳定性和准确度良好,具有快速、准确、简单的优点,能够满足药典中对重金属元素的限量要求,适用于现场快速检测与质量控制检测。     

Understanding the traditional aspect of Chinese medicine in order to achieve meaningful quality control of Chinese materia medica

Although sophisticated and technologically advanced, current quality control methods for Chinese medicines (syn. Chinese materia medica or CMM) lack comprehensiveness and practicability. They are more suited for analyzing single-chemical drugs or specific, known chemical components that have already been isolated. While these methods can fully satisfy the modern scientific requirements for identity, purity and quality in the assessment of chemical drugs, they are not suitable for handling the complex chemical nature of traditional CMM whose multifunctional components along with their inherent holistic activities are frequently unknown and thus are not adequately analyzed by these methods. In order to assess properly and meaningfully the identity and quality of complex CMM (also known as Chinese herbs and Chinese herbal medicines), additional measures that can retain the traditional aspect of CMM need to be included. This requires a basic understanding of traditional Chinese medicine (TCM).     

分子生物色谱用于中药活性成分筛选及质量控制方法的研究

报道了近期工作进展,首先阐述了分子生物色谱的基本原理及特点,然后介绍了分子生物色谱对多种中药、不同产地的同种中药活性成分谱图模式的比较,结合已有的工作对活性成分筛选方法、相互作用研究、质量控制方法发展做了细致的说明,并讨论了其发展方向及前景。     

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.     

Separation of anticancer medicines carmustine,lomustine, semustine and melphalan by PAMAM dendrimer: a theoretical study

Much progress has been made in the treatment of cancer. However, it remains a significant challenge to treat as toxic chemotherapeutic drugs are often poorly tolerated when administered together, limiting the patient’s treatment options. A possible solution to this problem is anchoring drugs on the surface of nanoparticles. These systems have a variety of structures with sizes, shapes and materials which determine loading capacity, cellular targeting and stability. Dendrimers are a class of nanoparticles which have been investigated in this context. In this study, we investigated the functionalization of polyamidoamine (PAMAM) dendrimers with some anticancer medications that suppresses the growth of cancer cells (carmustine, lomustine, semustine and melphalan; 1–4). The possibility of drug release, drug delivery and drug separation by PAMAM was theoretically investigated and discussed. The predicted theoretical method will be interesting to remove the pollutants from the medical solutions by PAMAM dendrimer nanoclusters. The results of the modeling were obtained by MMFF94 and RHF/PM6 methods for all form of the PAMAM–medicines complexes. The obtained results by these two methods were shown same trend of the relative energy surfaces of the complexes of PAMAM–medicines 1–4.     

气相色谱-质谱指纹图谱在甄别真假卷烟上的应用

运用固相微萃取／气相色谱-质谱法建立卷烟挥发性和半挥发性物质的指纹图谱。通过指纹图谱相似度评价软件,对12批正品卷烟和1个假冒品卷烟的指纹图谱进行了相似度计算,结果表明：12批样品间相似度很好,而假冒品卷烟与正品卷烟的相似度很低,该方法为探讨卷烟质量稳定和甄别真假卷烟提供了一种简便易行的方法模式。     

Editorial: Current Issues on Future Researches and Applications of Natural Product Medicines

The use of natural product medicine has emerged from traditional to modern therapy in order to increase the quality of health worldwide. To prove pharmacological effects of medicinal plants and to further develop the rational use of herbal medicines, scientific approaches are essential. The development of sciences and technologies have highly supported the research on natural product medicines in all aspects. Recent findings from research in natural product medicines were a major focus in the International Seminar on Natural Product Medicines 2012 which was held in Bandung and organized by School of Pharmacy, Bandung Institute of Technology (ITB) and Indonesian Society on Natural Product Researchers (PERHIPBA). Furthermore, there was an interesting sharing of experiences and knowledge on how to develop and practice some well-known traditional medicines such as Traditional Chinese Medicine (TCM), ayurveda and jamu