Detection of counterfeit stevia products using a handheld Raman spectrometer

Stevia is a highly appreciated natural sweetener because it can be consumed by diabetic patients. Due to the increasing popularity of stevia during the last years, counterfeit products have been making their way into the market. Raman spectroscopy is a versatile analytical technique that can be used for control tasks and handheld modern devices expand its possible applications to instant in situ measurements. The Raman spectra of six commercial stevia products (five purchased in Bolivia and one in Germany) were recorded and compared to the spectra of standards of rebaudioside A and stevioside as well as the spectra of the artificial sweeteners sodium cyclamate and sodium saccharin. Based on the Raman spectroscopic data, it was verified that three of the Bolivian products were counterfeit products and another one was rich in maltodextrin. The Raman spectra of one Bolivian product and the German one revealed rebaudioside A and stevioside as major components. Raman spectroscopy was capable of detecting contents as low as 5% (w/w) of sodium cyclamate during measurements of stevia-sodium cyclamate mixtures. The results show that Raman spectroscopy can successfully be used to detect counterfeit stevia and underline its high potential for the detection of food adulteration.     

Innovative high-performance liquid chromatography method development for the screening of 19 antimalarial drugs based on a generic approach, using design of experiments, independent component analysis and design space

An innovative methodology based on design of experiments (DoE), independent component analysis (ICA) and design space (DS) was developed in previous works and was tested out with a mixture of 19 antimalarial drugs. This global LC method development methodology (i.e. DoE-ICA-DS) was used to optimize the separation of 19 antimalarial drugs to obtain a screening method. DoE-ICA-DS methodology is fully compliant with the current trend of quality by design. DoE was used to define the set of experiments to model the retention times at the beginning, the apex and the end of each peak. Furthermore, ICA was used to numerically separate coeluting peaks and estimate their unbiased retention times. Gradient time, temperature and pH were selected as the factors of a full factorial design. These retention times were modelled by stepwise multiple linear regressions. A recently introduced critical quality attribute, namely the separation criterion (S), was also used to assess the quality of separations rather than using the resolution. Furthermore, the resulting mathematical models were also studied from a chromatographic point of view to understand and investigate the chromatographic behaviour of each compound. Good adequacies were found between the mathematical models and the expected chromatographic behaviours predicted by chromatographic theory. Finally, focusing at quality risk management, the DS was computed as the multidimensional subspace where the probability for the separation criterion to lie in acceptance limits was higher than a defined quality level. The DS was computed propagating the prediction error from the modelled responses to the quality criterion using Monte Carlo simulations. DoE-ICA-DS allowed encountering optimal operating conditions to obtain a robust screening method for the 19 considered antimalarial drugs in the framework of the fight against counterfeit medicines. Moreover and only on the basis of the same data set, a dedicated method for the determination of three antimalarial compounds in a pharmaceutical formulation was optimized to demonstrate both the efficiency and flexibility of the methodology proposed in the present study.     

红外光谱技术的三文鱼肉假冒鉴别

国内三文鱼市场鱼龙混杂,假冒问题严重,但鉴别方法有限。采用红外光谱技术结合偏最小二乘判别分析法(PLS-DA)研究了黑龙江大马哈鱼、淡水虹鳟、智利太平洋鲑三种鱼肉对挪威三文鱼的冒充问题。采用FITR光谱仪和KBr压片法采集四种肉类的原始光谱,并对原始光谱分别进行多元散射校正(MSC)、Savitzky-Golay平滑、一阶导数(first derivative)、标准正则变换(SNV)、峰面积归一化(peak area normalization)五种预处理来消除噪声等干扰因素并确定最佳预处理方法。为建立PLS-DA鉴别模型,将四种鱼肉的光谱分别赋予-3,-1,1和3四个参考分值,建模后通过预测检测集鱼肉得分来检验模型准确性。结果表明：采用峰面积归一化法时,PLS-DA检测模型的效果最好,校正集和交叉验证集的决定系数分别为0.97和0.95。RMSEC和RMSECV分别为0.37和0.52。该模型能显著区分四种鱼肉、检测集的预测分值分别聚集在各自的参考分值附近,在阈值为±1的判别条件下预测准确度为96%。同时采用马氏距离法进一步对四种鱼肉的光谱进行分析,发现相互之间差异明显,其中挪威三文鱼与其品种差别最大的淡水虹鳟距离最大,与其比较接近的智利太平洋鲑的距离最小,红外光谱信息能够反映不同鱼肉的品种、生活环境等差异。因此,采用红外光谱技术结合PLS-DA法能够准确的鉴别出其他鱼肉对挪威三文鱼的冒充问题,同时对其他肉类检测有一定借鉴意义。     

Anti-Quorum Sensing Activity of Stevia Extract,Stevioside, Rebaudioside A and Their Aglycon Steviol

Governments are creating regulations for consumers to reduce their sugar intake, prompting companies to increase the ratio of artificial sweeteners in their products. However, there is evidence of some deleterious effects ascribed to the aforementioned synthetic agents and therefore consumers and food manufacturers have turned their attention to natural dietary sweeteners, such as stevia, to meet their sweetening needs. Stevia is generally considered safe; however, emerging scientific evidence has implicated the agent in gut microbial imbalance. In general, regulation of microbial behavior is known to depend highly on signaling molecules via quorum sensing (QS) pathways. This is also true for the gut microbial community. We, therefore, evaluated the possible role of these stevia-based natural sweeteners on this bacterial communication pathway. The use of a commercial stevia herbal supplement resulted in an inhibitory effect on bacterial communication, with no observable bactericidal effect. Purified stevia extracts, including stevioside, rebaudioside A (Reb A), and steviol revealed a molecular interaction, and possible interruption of Gram-negative bacterial communication, via either the LasR or RhlR receptor. Our in-silico analyses suggest a competitive-type inhibitory role for steviol, while Reb A and stevioside are likely to inhibit LasR-mediated QS in a non-competitive manner. These results suggest the need for further safety studies on the agents.     

A simple,rapid, and robust “on-the-go” identity testing of biotherapeutics using FTIR spectroscopy

The stunning rise of biotherapeutics as successful treatments of complex and hard-to-treat diseases, in particular cancer, has necessitated the development of a rapid analytical method capable of differentiating these otherwise significantly similar antibody-based products. The existing methods for product identification pose significant drawbacks in terms of the consumption of time and labor. Here, we present an FTIR spectroscopy-based simple, rapid, and robust method that is capable of differentiating between the biotherapeutics (both innovator products and biosimilars). The proposed approach uses partial least-squares-discriminant analysis to pinpoint subtle differences in the FTIR spectra of the samples, enabling us to not only identify the product but also calculate its concentration. This FTIR-based method can be used to fulfill the identity testing requirement of a pharmaceutical drug in its final packaged form set by the US Food and Drug Administration. Along with this, identity testing can also be deployed at multiple steps in the manufacturing process and can also be used by the appropriate regulatory or government agency for tackling counterfeits of biotherapeutic products.     

Liquid chromatography with tandem mass spectrometry for the simultaneous identification and quantification of cardiovascular drugs applied to the detection of substandard and falsified drugs

The counterfeiting of pharmaceuticals has been detected since about 1990 and has alarmingly continued to pick up steam. We have been recently involved in an evaluation program of some of the most commonly prescribed cardiovascular drugs in Africa, for analysing an important number of tablets or capsules obtained from different places in seven African countries. A reversed‐phase high‐performance liquid chromatography with tandem mass spectrometry method was developed and validated to simultaneously control the identity and the quantity of acenocoumarol, amlodipine, atenolol, captopril, furosemide, hydrochlorothiazide and simvastatin in tablets. Their separation was performed on a Kinetex® C₁₈ (100 mm × 2.1 mm inside diameter, 2.6 μm) column using a gradient elution of 20 mM ammonium formate buffer and acetonitrile (90:10 10:90 v/v) at a flow rate of 0.5 mL/min. The analytes were detected using electrospray ionisation tandem mass spectrometry in both positive and negative modes with multiple reaction monitoring. Tandem mass spectrometry fragmentation patterns of captopril, furosemide and acenocoumarol, up to now not detailed in the literature, were also studied to assist in the selection of the most relevant transitions towards the objectives. The developed method was validated as per International Conference on Harmonisation guidelines with respect to specificity, linearity, trueness, precision, limits of detection and quantification. It has been successfully applied to the control of oral forms of seven cardiovascular drugs collected in African countries.     

Rapid discrimination of slimming capsules based on illegal additives by electronic nose and flash gas chromatography

The discrimination of counterfeit and/or illegally manufactured medicines is an important task in the pharmaceutical industry for pharmaceutical safety. In this study, 22 slimming capsule samples with illegally added sibutramine and phenolphthalein were analyzed by electronic nose and flash gas chromatography. To reveal the difference among the different classes of samples, principal component analysis and linear discriminant analysis were employed to analyze the data acquired from electronic nose and flash gas chromatography, respectively. The samples without illegal additives can be discriminated from the ones with illegal additives by using electronic nose or flash gas chromatography data individually. To improve the performance of classification, a data fusion strategy was applied to integrate the data from electronic nose and flash gas chromatography data into a single model. The results show that the samples with phenolphthalein, sibutramine and both can be classified well by using fused data.     

搜索两个不同坏硬币的最优化方法

设n个外观相同的硬币的集合X中含有两个坏硬币，这两个坏硬币的重量彼此不同，但都比好硬币重，而假定好硬币有相同的重量．以g2（n）表示用天平从X中找出两个坏硬币的最少测试次数．本文证明了对任意的n成立［log3（n2）］≤g2（n）≤［log3（n2）］＋1．且对无穷多个n，文中所给的测试过程是最优的．     

Forensic applications of ambient ionization mass spectrometry

This review highlights and critically assesses forensic applications in the developing field of ambient ionization mass spectrometry. Ambient ionization methods permit the ionization of samples outside the mass spectrometer in the ordinary atmosphere, with minimal sample preparation. Several ambient ionization methods have been created since 2004 and they utilize different mechanisms to create ions for mass-spectrometric analysis. Forensic applications of these techniques—to the analysis of toxic industrial compounds, chemical warfare agents, illicit drugs and formulations, explosives, foodstuff, inks, fingerprints, and skin—are reviewed. The minimal sample pretreatment needed is illustrated with examples of analysis from complex matrices (e.g., food) on various substrates (e.g., paper). The low limits of detection achieved by most of the ambient ionization methods for compounds of forensic interest readily offer qualitative confirmation of chemical identity; in some cases quantitative data are also available. The forensic applications of ambient ionization methods are a growing research field and there are still many types of applications which remain to be explored, particularly those involving on-site analysis. Aspects of ambient ionization currently undergoing rapid development include molecular imaging and increased detection specificity through simultaneous chemical reaction and ionization by addition of appropriate chemical reagents.     

基于THz光谱成像的纸币真伪鉴别研究

根据纸币防伪特征区域载体材料与制作工艺的不同,利用透射式太赫兹脉冲成像技术对2005版真伪百元人民币的白水印和安全线两处防伪特征区域进行逐点扫描获取相应的太赫兹时域信号,然后对太赫兹波形进行数据处理获得时域显示模式成像及频域显示模式成像。将真钞和假钞的成像结果进行对比,发现白水印、安全线部位的真假钞成像结果区别明显,证实太赫兹脉冲成像技术能够真实、有效地对真假人民币进行多区域、多维度的准确鉴定。