Quantitative Analysis of Sildenafil and Tadalafil in Various Fake Drugs Recently Distributed in Korea

Abstract: Illicit distribution of various illicit or counterfeit drugs containing sildenafil and tadalafil has increased and caused noticeable problems in Korea. This study has been performed to determine the content range of sildenafil and tadalafil in various fake drugs. Among the illicit or counterfeit drugs seized by Korean authorities, 105 exhibits were used for the quantification. HPLC–UV analysis of methanol extractions was used for separation and quantitation of the two target compounds. The most abundant type of fake drug was counterfeit Viagra^® tablets. Sildenafil was found in 73 exhibits, and tadalafil was found in seven exhibits. Twenty‐five exhibits out of the 105 contained both sildenafil and tadalafil. The contents of sildenafil ranged from 4.3 to 453.2 mg; for tadalafil, the range was 2.2–40.4 mg. The proportion of cases of having more than 100 mg of sildenafil was 50% and 78% had more than 20 mg of tadalafil.     

Detection of counterfeit antiviral drug Heptodin™ and classification of counterfeits using isotope amount ratio measurements by multicollector inductively coupled plasma mass spectrometry (MC-ICPMS) and isotope ratio mass spectrometry (IRMS)

Isotope ratio mass spectrometry (IRMS) and multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS) are highly important techniques that can provide forensic evidence that otherwise would not be available. MC-ICP-MS has proved to be a very powerful tool for measuring high precision and accuracy isotope amount ratios. In this work, the potential of combining isotope amount ratio measurements performed by MC-ICP-MS and IRMS for the detection of counterfeit pharmaceutical tablets has been investigated.An extensive study for the antiviral drug Heptodin™ has been performed for several isotopic ratios combining MC-ICP-MS and an elemental analyser EA-IRMS for stable isotope amount ratio measurements. The study has been carried out for 139 batches of the antiviral drug and analyses have been performed for C, S, N and Mg isotope ratios. Authenticity ranges have been obtained for each isotopic system and combined to generate a unique multi-isotopic pattern only present in the genuine tablets. Counterfeit tablets have then been identified as those tablets with an isotopic fingerprint outside the genuine isotopic range.The combination of those two techniques has therefore great potential for pharmaceutical counterfeit detection. A much greater power of discrimination is obtained when at least three isotopic systems are combined. The data from these studies could be presented as evidence in court and therefore methods need to be validated to support their credibility. It is also crucial to be able to produce uncertainty values associated to the isotope amount ratio measurements so that significant differences can be identified and the genuineness of a sample can be assessed.     

Objective ink color comparison through image processing and machine learning

Making changes or additions to written entries in a document can be profitable and illegal at the same time. A simple univariate approach is first used in this paper to quantify the evidential value in color measurements for inks on a document coming from a different or the same source. Graphic, qualitative discrimination is then obtained independently by applying color deconvolution image processing to document images, with parameters optionally optimized by support vector machines (SVM), a machine learning method. Discrimination based on qualitative results from image processing is finally compared to the quantitative results of the statistical approach. As color differences increase, optimized color deconvolution achieves qualitative discrimination when the statistical approach indicates evidence for the different source hypothesis.     

机制版假币票面上印刷疵点的检验

目的分析假币票样上的印刷疵点,为串并假币机制版印制点提供科学依据。方法通过图文扫描和图象处理技术,获取假币票面上的印刷疵点信息,研究梳理不同票面上一致的疵点组合,寻找其与印版的相关性,继而推导与印制者的相关性。结果找到可以表征相同胶片版或PS版的不同冠字号码假币票样上一致的印刷疵点。结论可以通过图文扫描和图象处理手段得到印刷疵点特征。     

Automated detection and classification of counterfeit banknotes using quantitative features captured by spectral-domain optical coherence tomography

Counterfeiting of banknotes is still a severe crime problem in many countries. One of the most significant issue for solving the crime is to classify the counterfeit types and identify the sources. Most of the current methods to classify counterfeit banknotes rely on manual examination that is time-consuming and labor-intensive. Moreover, these methods only detect surface features which can be easily imitated through advanced printing technology. In this study, an automated method based on optical coherence tomography (OCT) and machine-learning algorithms was proposed to classify different types of banknotes based on the internal features. A spectral-domain OCT (SD-OCT) system was employed for sub-surface imaging and quantitative assessment of banknotes. A total of 29 Chinese 100-Yuan banknotes were collected, in which 4 of them were real and 25 of them were counterfeiting by three different printing processes. Each banknote was imaged 10 times in 3 distinct regions, which resulted in a dataset of 290 samples. Each sample was characterized by extracting 2 A-scan (OCT signal intensity along depth) based features and 14B-scan (cross-sectional OCT images) based features. Several machine-learning models, including logistic regression (LR), support vector machines (SVM), K-nearest neighbor (KNN) and random forest (RF), were built and optimized as the classifiers that were trained using 203 samples and applied to predict 87 testing samples. The best performance was achieved by SVM classifier in which the sensitivity of 96.55% and specificity of 98.85% were obtained in discriminating between authentic and counterfeit banknotes, and the sensitivity of 94.67% and specificity of 98.22% were obtained in predicting the types of counterfeit banknotes. These classifiers were also evaluated using the receiver operating characteristic (ROC) curves. To the best of our knowledge, this is the first study where A-scan and B-scan derived features from OCT images have been used for the detection and classification of different types of counterfeit banknotes.     

基层医疗机构假药劣药销售监管制度的法律剖析

本文从一起医疗机构销售假、劣药的案件谈起，通过焦点案情分析，引发对基层医疗机构假、劣药销售监管制度的深层次的法律剖析。文章首先采用现代法学理论的成因分析方法对基层医疗机构销售假、劣药品行为进行分析，研究其违法动机、违法方式和违法目的。而后在成因分析的基础上，运用比较法的方法，对中美相关制度进行比较。最后对基层医疗机构销售假、劣药的监管制度提出了一些合理化的建议。     

Identifying Counterfeit Cigarettes Using Environmental Pollen Analysis: An Improved Procedure*

Traditional pollen preparation techniques provide clear residues for pollen identification; however, such methods are time-consuming, requiring repeated centrifugation, heating, and digestion with high-concentration hazardous chemicals. Tobacco leaves can effectively trap environmental pollen due to hairy surface and terpene-rich exudates. A new tobacco sample processing method was developed by using different extraction chemistry with surfactant. Marlboro Gold cigarettes were employed as model samples for method development. Parameters critical for pollen extraction, which include number of cigarette sticks used, extraction solution, and extraction temperature, were optimized. By using 1% dishwashing detergent to treat three cigarettes at room temperature, the improved method was able to recover sufficient pollen for microscopic analysis in three repeated centrifuge-washing steps and omit hazardous chemicals involved in traditional methods. We focused on the pollen of common ragweed (Ambrosia artemisiifolia), a plant native to North America, as an indicator to differentiate genuine and counterfeit U.S. brand cigarettes. Results from analyzing randomly purchased genuine (authenticated by forensic examination) and known counterfeit Marlboro Gold provided by law enforcement revealed that a significant amount (39%) of Ambrosia were consistently present in all genuine samples, while counterfeit contained none or only trace count. Similar results were found in other counterfeit U.S. brand cigarettes (all seized in the U.S.) involved in this study as well. Lack of Ambrosia in cigarette strongly indicates the product was not originated in the United States.     

Classification algorithm using halftone features of counterfeit bills and CNN

With recent advancements in image processing and printing technology, home printers have improved in performance and grown more widespread. As such, they have been increasingly used in counterfeiting and forgery. Most counterfeit bills in Korea have been created using home scanners and printers. The identification of printer model is thus necessary to rapidly track down criminals and solve crimes. Household printers can be largely divided into inkjet and laser printers. These two types of printers print halftone textures instead of continuous images. This study proposed a technique of printer classification based on halftone textures that can be observed in printed documents. Since halftone textures are expressed as periodic lattices, the images were transformed via FFT, which is highly effective at expressing periodicity. ResNet, known for its superior gradient flow, was used for training. The experiment was conducted on 12 color laser jets and 2 inkjets. Scans of bills printed by each printer were used, and halftone texture analysis was performed on these images for printer model classification. Each image was cropped into several parts; one of the cropped parts was analyzed. The analysis showed that laser printers could be 100% distinguished from inkjet printers. An accuracy of 98.44% was achieved in make classification. When 50 cropped images were used instead of a single image, the technique achieved 100% accuracy in model classification. The proposed technique is non-destructive; it offers high accessibility and efficiency as it can be performed using a scanner alone, without requiring additional optical equipment.     

伪造2005版100元人民币水印特征初探

目的建立伪造2005版100元人民币水印检验方法。方法利用紫外光源、透光光源对伪造人民币上水印进行显现和检验。结果伪造黑水印、伪造白水印在印刷方式、印刷工艺及图文形态等特征上存在不同。结论本方法的建立,可为识别假币制作地点提供线索。     

Development of a real-time PCR assay to control the illegal trade of meat from protected capercaillie species (Tetrao urogallus)

A rapid and highly species-specific real-time polymerase chain reaction (PCR) assay has been developed for the detection of capercaillie DNA (Tetrao urogallus) in meat and meat mixtures. The method combines the use of capercaillie-specific primers, that amplify a 142bp fragment of the mitochondrial 12S rRNA gene, and a positive control primer pair that amplifies a 141bp fragment of the nuclear 18S rRNA gene from eukaryotic DNA. SYBR(?) Green dye or TaqMan(?) fluorogenic probes were used to monitor the amplification of the target genes. Results obtained with the use of TaqMan(?) probes as detection platform increased the specificity of the real-time PCR assay in comparison with the results obtained using SYBR(?) Green. The proposed real-time PCR assay represents a rapid and straightforward method for the accurate identification of capercaillie that could be used by law enforcement agencies as a tool for the control of poaching and illegal trade of meat from this protected species.     

Classification of prepaid cards based on multivariate treatment of data obtained by X-ray fluorescence analysis

Two hundred prepaid cards, which had been used in Nagoya-city's subway in Japan, and another 32 prepaid cards (11 were real turnpike cards, 20 were counterfeit cards and 1 was a white card) were evaluated by X-ray fluorescence (XRF) without any pre-treatment. A preliminary investigation was performed on 200 prepaid cards in order to find an identification method for the turnpike cards. By plotting the relative intensity of titanium versus that of iron obtained by XRF, the cards were clearly classified into seven groups. On the other hand, the cards could be divided into four groups by a multivariate analysis using the relative intensities of five elements such as chlorine, calcium or tin, titanium, iron and barium. Using these results to classify the Japanese turnpike cards, they were divided into three groups or two groups. One of three groups or two groups was the counterfeit card group.     

Analyzing Brazilian vehicle documents for authenticity by easy ambient sonic-spray ionization mass spectrometry

Using desorption/ionization techniques such as easy ambient sonic-spray ionization mass spectrometry (EASI-MS), it is possible to analyze documents of Brazilian vehicles for authenticity, providing a chemical profile directly from the surface of each document. A method for the detection of counterfeit documents is described, and the falsification procedure is elucidated. Forty authentic and counterfeit documents were analyzed by both positive and negative ion modes, EASI(±)-MS. EASI(+)-MS results identified the presence of (bis(2-ethylhexyl)phthalate plasticizer and of dihexadecyldimethylammonium biocide in both types of documents. For EASI(-)-MS results, the 4-octyloxybenzoic acid additive ([M + H](+): m/z 249) is present only in counterfeit documents. It was also found that counterfeit vehicle documents are produced via Laserjet printers. Desorption/ionization techniques, such as EASI-MS, offer therefore, an intelligent way to characterize the counterfeiting method.     

Computation of likelihood ratios in fingerprint identification for configurations of three minutiae

Recent challenges to fingerprint evidence have brought forward the need for peer-reviewed scientific publications to support the evidential value assessment of fingerprint. This paper proposes some research directions to gather statistical knowledge of the within-source and between-sources variability of configurations of three minutiae on fingermarks and fingerprints. This paper proposes the use of the likelihood ratio (LR) approach to assess the value of fingerprint evidence. The model explores the statistical contribution of configurations of three minutiae using Tippett plots and related measures to assess the quality of the system. Features vectors used for statistical analysis have been obtained following a preprocessing step based on Gabor filtering and image processing to extract minutia position, type, and direction. Spatial relationships have been coded using Delaunay triangulation. The metric, used to assess similarity between two feature vectors is based on an Euclidean distance measure. The within-source variability has been estimated using a sample of 216 fingerprints from four fingers (two donors). Between-sources variability takes advantage of a database of 818 ulnar loops from randomly selected males. The results show that the data-driven approach adopted here is robust. The magnitude of LRs obtained under the prosecution and defense propositions stresses upon the major evidential contribution that small portions of fingermark, containing three minutiae, can provide regardless of its position on the general pattern.     

Characterization of allegedly musk-containing medicinal products in Taiwan

As a highly valued ingredient of Chinese medicinal remedies, musk is used as a detoxification agent and for treating fever, inflammation and swelling, and pain. Muscone (3-methylcyclopentadecanone-1), an odoriferous secretion from the ventral glands of male musk deer, is believed to be the active ingredient. A small amount of muscopyridine is also found in the secretion from the ventral glands of male musk deer. Common counterfeit ingredients are musk xylene, musk ambrette, musk ketone, and diphenhydramine. An extraction/GC-MS protocol/data evaluation scheme was developed and applied to study allegedly musk-containing Musk-Tiger Bone Plaster preparations and musk pods (or grains) from Chinese medicine stores and an airport customs. The content of muscone in a specific sample was estimated based on the percentage of the amount recovered from the first extraction. No muscone or counterfeit ingredients were found in all musk pod (or grain) samples from the customs and in the majority of Musk-Tiger Bone Plaster preparations, while muscone (alone or with counterfeit ingredients) was found in most of the musk pod (or grain) collected from Chinese medicine stores.     

X‐ray Powder Diffraction for Characterization of Raw Materials in Banknotes

We report about the X‐ray powder diffraction characterization of crystalline materials used to produce genuine and counterfeit banknotes, performed with a single‐crystal diffractometer that permits fast and nondestructive measurements in different 0.5‐mm sized areas; 20‐euro denomination genuine banknotes were analyzed, and results were compared with counterfeit banknotes. The analysis shows that the papers used to print real banknotes are composed, as expected, of cotton‐based cellulose and titanium dioxide as crystalline additive, but different polymorphs of TiO₂ for different emission countries are evidenced. The counterfeit banknotes are composed of cellulose based on wood pulp; moreover, an unexpected significant quantity of TiO₂ was found to be mixed with calcite, indicating that the paper employed by forgers is not simply a common low‐cost type. The crystalline index and intensity ratios between the peaks attributable to cellulose and fillers can provide additional information to trace back paper suppliers for forensic purposes.     

A review of recent advances in impurity profiling of illicit MDMA samples

Profiling illicit ecstasy tablets has the potential to become an invaluable tool in the crackdown on drug trafficking, but that potential has yet to be fully realized. The impurity profile of an ecstasy tablet can be used to determine the method employed to synthesize the actual controlled substance, which in most cases, is 3,4-methylenedioxymethamphetamine (MDMA). Tablets can then be linked to a common synthetic route, potentially to a common manufacturer, and possibly even to a common manufacturing batch, based on the impurities present. Current methods for profiling MDMA tablets typically involve extracting the organic impurities for analysis by gas chromatography-mass spectrometry. The potential of profiling the trace metals present in tablets has begun to be investigated while more robust statistical and chemometric procedures are being applied to compare and link tablets. This article reviews the recent advances in MDMA impurity profiling from 2002 up to the end of 2006.     

发光光谱成像检验人民币真伪研究

目的建立鉴别人民币真伪和假币来源同一的检验方法。方法运用发光光谱成像技术对1999版和2005版真币人民币各50张、1999版和2005版假币各12张进行检验。结果真假人民币之间和不同来源的假币之间均能较好的区分开,区分效果明显。结论发光光谱成像技术可以有效鉴别真假人民币和假币来源是否同一。     

Passport examination by a confocal-type laser profile microscope

The author proposes a nondestructive and highly precise method of measuring the thickness of a film pasted on a passport using a confocal-type laser profile microscope. The effectiveness of this method in passport examination is demonstrated. A confocal-type laser profile microscope is used to create profiles of the film surface and film–paper interface; these profiles are used to calculate the film thickness by employing an algorithm developed by the author. The film thicknesses of the passport samples—35 genuine and 80 counterfeit Japanese passports—are measured nondestructively. The intra-sample standard deviation of the film thicknesses of the genuine and counterfeit Japanese passports was of the order of 1 μm The intersample standard deviations of the film thicknesses of passports forged using the same tools and techniques are expected to be of the order of 1 μm. The thickness values of the films on the machine-readable genuine passports ranged between 31.95 μm and 36.95 μm. The likelihood ratio of this method in the authentication of machine-readable Japanese genuine passports is 11.7. Therefore, this method is effective for the authentification of genuine passports. Since the distribution of the film thickness of all forged passports was considerably larger than the accuracy of this method, this method is considered effective also for revealing the relation among the forged passports and acquiring proof of the crime.     

Automated shape annotation for illicit tablet preparations: A contour angle based classification from digital images

In order to facilitate forensic intelligence efforts in managing large collections of physical feature data pertaining to illicit tablets, we have developed an automated shape classification method. This approach performs categorical shape annotation for the domain of illicit tablets. It is invariant to scale, rotation and translation and operates on digital images of seized tablets. The approach employs two processing levels. The first (coarse) level is being based on comparing the contour curvature space of tablet pairs. The second (fine) level is a rule based approach, implemented as a classification tree, that exploits characteristic similarities of shape categories. Annotation is demonstrated over a collection of 169 tablets selected for their diverse shapes with an accuracy of 97.6% when 19 shape categories are defined.     

Development of a Library Search‐Based Screening System for 3,4‐Methylenedioxymethamphetamine in Ecstasy Tablets Using a Portable Near‐Infrared Spectrometer

This is the first report on development of a library search‐based screening system for 3,4‐methylenedioxymethamphetamine (MDMA) in ecstasy tablets using a portable near‐infrared (NIR) spectrometer. The spectrum library consisted of spectra originating from standard substances as well as mixtures of MDMA hydrochloride (MDMA‐HCl) and diluents. The raw NIR spectra were mathematically pretreated, and then, a library search was performed using correlation coefficient. To enhance the discrimination ability, the wavelength used for the library search was limited. Mixtures of MDMA‐HCl and diluents were used to decide criteria to judge MDMA‐positive or MDMA‐negative. Confiscated MDMA tablets and medicinal tablets were used for performance check of the criteria. Twenty‐two of 27 MDMA tablets were truly judged as MDMA‐positive. Five false‐negative results may be caused by compounds not included in the library. No false‐positive results were obtained for medicinal tablets. This system will be a useful tool for on‐site screening of MDMA tablets.