Profiling of counterfeit medicines by vibrational spectroscopy

Counterfeit pharmaceutical products have become a widespread problem in the last decade. Various analytical techniques have been applied to discriminate between genuine and counterfeit products. Among these, Near-infrared (NIR) and Raman spectroscopy provided promising results. The present study offers a methodology allowing to provide more valuable information for organisations engaged in the fight against counterfeiting of medicines. A database was established by analyzing counterfeits of a particular pharmaceutical product using Near-infrared (NIR) and Raman spectroscopy. Unsupervised chemometric techniques (i.e. principal component analysis - PCA and hierarchical cluster analysis - HCA) were implemented to identify the classes within the datasets. Gas Chromatography coupled to Mass Spectrometry (GC-MS) and Fourier Transform Infrared Spectroscopy (FT-IR) were used to determine the number of different chemical profiles within the counterfeits. A comparison with the classes established by NIR and Raman spectroscopy allowed to evaluate the discriminating power provided by these techniques. Supervised classifiers (i.e. k-Nearest Neighbors, Partial Least Squares Discriminant Analysis, Probabilistic Neural Networks and Counterpropagation Artificial Neural Networks) were applied on the acquired NIR and Raman spectra and the results were compared to the ones provided by the unsupervised classifiers. The retained strategy for routine applications, founded on the classes identified by NIR and Raman spectroscopy, uses a classification algorithm based on distance measures and Receiver Operating Characteristics (ROC) curves. The model is able to compare the spectrum of a new counterfeit with that of previously analyzed products and to determine if a new specimen belongs to one of the existing classes, consequently allowing to establish a link with other counterfeits of the database.     

差示扫描量热法检验猎枪弹丸

目的对不同厂家的猎枪弹丸进行区分和鉴别。方法使用功率补偿型差示扫描量热仪(DSC)对4种不同品牌的猎枪弹丸进行分析。结果可测得每种弹丸的DSC曲线和熔点温度Tm,熔融峰温Tmp,熔化焓ΔHm等热学参数。结论利用差示扫描量热法可以对不同品牌的猎枪弹丸进行鉴别,该方法为办案过程中遇到同号数不同品牌的猎枪弹丸鉴别提供了一种有效技术手段。     

差示扫描量热法检验合成纤维

目的研究不同种类合成纤维以及不同厂家生产的同种类合成纤维的鉴别方法。方法应用功率补偿型差示扫描量热仪测定涤纶、腈纶、锦纶、丙纶、氨纶、氯纶等6种常见合成纤维和10个厂家生产的涤纶纤维的DSC曲线,并对热学参数进行计算和分析。结果涤纶、腈纶、锦纶、丙纶、氨纶、氯纶的DSC曲线明显不同,10个厂家生产的涤纶纤维的DSC曲线虽然非常相近,但对其熔融温度Tm、熔融峰顶温度Tmp、熔融焓变ΔHm、结晶温度Tc、结晶峰顶温度Tcp和结晶焓变ΔHc等热学参数的计算结果显示,10个涤纶纤维的参数并不完全相同。结论差示扫描量热法不但能对不同种类的合成纤维进行鉴别,也可区分不同厂家生产的同种类纤维,从而为案件侦破提供更为准确的方向、线索和证据。     

Evaluation of the composition of street cocaine seized in two regions of Brazil

This work evaluates cocaine purity and the concentration ranges of adulterants and inorganic constituents for 31 street cocaine samples seized in two different regions of Brazil from July 2008 to May 2010. Cocaine and adulterants, such as caffeine, lidocaine and benzocaine, were quantified by Gas chromatography–mass spectrometry (GC–MS), and the inorganic constituents were determined by Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) and ion chromatography (IC). The cocaine concentrations in the samples seized in the Amazonas state (AM samples) ranged from 154 to 978 mg g^? 1, and these samples did not contain any of the adulterants studied. The cocaine concentrations in the samples seized in the Minas Gerais state (MG samples) ranged from 63.9 to 753 mg g^? 1. Caffeine was the main adulterant found in 76% of the MG samples, ranging in concentration from 5.5 to 645.3 mg g^? 1. Lidocaine was found in 66.7% of the MG samples, with concentrations ranging from 16.3 to 576.7 mg g^? 1. Benzocaine was found in only one MG sample, at a concentration of 84.8 mg g^? 1. Fourteen elements were identified by ICP-OES, and a wide variation was observed in the concentrations of Ca, Mg, Na, P, Al, Fe, Mn and Zn. Pearson Product–moment Correlations between the analytes allowed the constituents to be associated with the chemicals used in the manufacturing of cocaine and with some common diluents. The study of the purity of cocaine and the presence and concentration of adulterants and inorganic constituents is important because the latter can have deleterious effects on health.     

Detection and Classification of Ignitable Liquid Residues in the Presence of Matrix Interferences by Using Direct Analysis in Real Time Mass Spectrometry,

Conventional Gas Chromatography‐Mass Spectrometry (GC‐MS) methods for the analysis of ignitable liquids (ILs) are usually time‐consuming, and the data produced are difficult to interpret. A fast IL screening method using direct analysis in real time mass spectrometry (DART‐MS) is proposed in this study. GC‐MS, QuickStrip DART‐MS, and thermal desorption DART‐MS methods were used to analyze neat ILs and thermal desorption DART‐MS without extraction was used to analyze ILs on five substrates (e.g., carpet, wood, cloth, sand, and paper). Compared to GC‐MS, DART‐MS methods generated different spectral profiles for neat ILs with more peaks in the higher mass range and also provided better detection of less volatile compounds. ILs on substrates were successfully classified (98 ± 1%) using partial least squares discriminant analysis (PLS‐DA) models based on thermal desorption DART‐MS data. This study shows that DART‐MS has great potential for the high‐throughput screening of ILs on substrates.     

Characterization of an odor permeable membrane device for the storage of explosives and use as canine training aids

The storage and use of explosives is regulated at the state and federal level, with a particular focus on physical security and rigorous accounting of the explosive inventory. For those working with explosives for the training and testing of explosive-detecting canines, cross-contamination is an important concern. Hence, explosives intended for use with canine teams must be placed into secondary storage containers that are new, clean, and airtight. A variety of containers meet these requirements and include screw-top glass jars (e.g., mason jars). However, an additional need from the explosive-detecting canine community is secondary containers that can also be used as training aids whereby the volatiles emitted by explosives are emitted in a predictable and stable manner. Currently, a generally accepted method for the storage of explosives and controlled emission of explosive vapor for canine detection does not exist. Ideally, such containers should allow odor to escape from the training aid but block external contaminates such as particulates or other volatiles. One method in use places the explosive inside a permeable cotton bag when in use for training and then stores the cotton bag inside an impermeable nylon bag for long-term storage. This paper describes the testing of an odor permeable membrane device (OPMD) as a new way to store and deploy training aids. We measured the evaporation rate and flux of various liquid explosives and volatile compounds that have been identified in the headspace of actual explosives. OPMDs were used in addition to traditional storage containers to monitor the contamination and degradation of 14 explosives used as canine training aids. Explosives were stored individually using traditional storage bags or inside an OPMD at two locations, one of which actively used the training aids. Samples from each storage type at both locations were collected at 0, 3, 6, and 9 months and analyzed using Fourier Transform Infrared (FTIR) Spectroscopy and Gas Chromatography–Mass Spectrometry (GC–MS) with Solid-Phase Microextraction (SPME). FTIR analyses showed no signs of degradation. GC–MS identified cross-contamination from ethylene glycol dinitrate (EGDN) and/or 2,3-dimethyl-2,3-dinitrobutane (DMNB) across almost all samples regardless of storage condition. The contamination was found to be higher among training aids that were stored in traditional ways and that were in active use by canine teams.     

GC/MS/AMDIS法检测火场常见基质中的汽油目标成分残留

目的考察研究15种汽油目标化合物,在不同火场情况下的不同燃烧残留基质中残留特点和存在规律。方法通过模拟混凝土、土壤和木材三种常见火场残留基质的不同燃烧情况和受灭火用水的影响,结合汽油水洗试验,利用气质联用/自动质谱去卷积分及鉴别系统（GC/MS/AMDIS）进行检测分析。结果混凝土、土壤和木材三种基质点燃至自然熄灭并未受外界因素影响下,能够全部检出15种目标化合物;在燃烧过程中并用水扑灭的情况下,混凝土和土壤中未检出2-甲基萘,而木材中未检出1,3-二甲基萘;在自然熄灭并用水冲洗情况下,混凝土和土壤中均未检出1,3,5-三甲苯、十二烷和1,3-二甲基萘,同时土壤中也未检出2-甲基萘,而木材中未检出十二烷和2,3-二甲基萘。此外,水洗实验表明汽油中1,3,5-三甲苯等9种目标化合物易受水洗损失。结论根据所考察的汽油目标化合物残留特点,可以在目标成分不完全检出的信息缺损条件下,为判定火场中汽油存在提供一定的依据。     

基于GC-MS的血液气味识别模型

目的阐明人体血液与动物血液气味的差异性,并建立对两者进行分辨的仪器分析方法。方法采用气相色谱-质谱技术联合固相微萃取前处理方法测定了血液气味的化学组成;以血液气味色谱数据为基础,利用逐步判别分析法,以Matlab为计算工具,编写了血液气味识别模型的代码。结果分析鉴定了9种在人体血液与动物血液之间有显著差异性的化学成分,基于这些化合物建立了血液气味识别模型。结论人体血液与动物血液气味有显著差别;建立的血液气味识别模型能够正确区分人体血液与动物血液。     

The analysis of tire rubber traces collected after braking incidents using Pyrolysis-GasChromatography/Mass Spectrometry

Automobile tire marks can routinely be found at the scenes of crime, particularly hit-and-run accidents and are left on road surfaces because of sudden braking or the wheels spinning. The tire marks are left due to the friction between the tire rubber and the solid road surface, and do not always demonstrate the tire tread pattern. However, the tire mark will contain traces of the tire. In this study, Pyrolysis Gas Chromatography/Mass Spectrometry was used to analyze 12 tires from different manufacturer's and their traces collected after braking incidents. Tire marks were left on a conglomerate road surface with sudden braking. The samples were pyrolysed without removal of contaminant in a micro-furnace type pyrolyser. Quantitative and qualitative analysis were performed on all the samples. All 12 samples were distinguished from each other. Each of the tire traces were identified as coming from there original source.     

Capillary gas chromatographic analysis of illicit diamorphine preparations

An improved capillary gas chromatographic method for the analysis of illicit diamorphine preparation is reported. The method was able to resolve the impurities and more frequent adulterants and contaminants present in street heroin preparations with a diamorphine detection limit of 0.2 ng in split-less mode.     

Identification of Different Forms of Cocaine and Substances Used in Adulteration Using Near‐infrared Raman Spectroscopy and Infrared Absorption Spectroscopy

Identification of cocaine and subsequent quantification immediately after seizure are problems for the police in developing countries such as Brazil. This work proposes a comparison between the Raman and FT‐IR techniques as methods to identify cocaine, the adulterants used to increase volume, and possible degradation products in samples seized by the police. Near‐infrared Raman spectra (785 nm excitation, 10 sec exposure time) and FT‐IR‐ATR spectra were obtained from different samples of street cocaine and some substances commonly used as adulterants. Freebase powder, hydrochloride powder, and crack rock can be distinguished by both Raman and FT‐IR spectroscopies, revealing differences in their chemical structure. Most of the samples showed characteristic peaks of degradation products such as benzoylecgonine and benzoic acid, and some presented evidence of adulteration with aluminum sulfate and sodium carbonate. Raman spectroscopy is better than FT‐IR for identifying benzoic acid and inorganic adulterants in cocaine.     

Background survey of polyethylene in the Australian Capital Territory – A demonstration of variability in isotopic abundance values and their application to forensic casework

Plastics including adhesive tapes, cable ties, and packaging are common evidence types encountered in forensic investigations and casework. Traditional examination techniques such as Fourier Transform Infrared (FTIR) spectroscopy lack specificity and are unable to discern differences within the same polymer structures leaving the analyst with a generic identification. High quality manufacturing methods further amplify the limitations in detecting variability between samples. Isotope Ratio Mass Spectrometry (IRMS) has been shown to be a valuable technique in further discriminating plastics. Discrimination is achieved by analysing the relative abundances of stable isotopes within a sample, with differences detected in isotope ratios possibly attributed to the source of raw materials and fractionation during the manufacturing process. A survey of cling wraps and re-sealable zipper storage bags collected in the Australian Capital Territory was undertaken to assess the variability in carbon and hydrogen isotope ratios of different brands and samples. The results of this research are discussed, particularly with respect to within and between brand trends, and a case study is presented as an example of the value of including IRMS in a casework context.     

Determination of impurities in illicit methamphetamine samples seized in Iran

In this study fifty samples of crystalline methamphetamine obtained from antinarcotics police of Iran seized during the year 2010 were analyzed. In order to determine the chemical characteristics of these samples, anion test, Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were carried out on the samples. All of the samples containing methamphetamine tested positive for chloride anion. The range of methamphetamine hydrochloride content in these samples was 33-95%. One sample out of 50 contained no methamphetamine. The fact that 1,2-dimethyl-3-phenylaziridine was the most frequently found impurity in the analyzed samples, indicates that most of the methamphetamine samples seized in Iran have been synthesized from pseudoephedrine as starting material.     

Drugged drivers in Norway with benzodiazepine detections

Norwegian drugged drivers with benzodiazepine (BZD) detections have been studied with regard to drug use pattern and rearrest rate. During 1995, 3343 drivers were apprehended by the police in Norway due to the suspicion of influence by drugs. Blood samples from all drivers were sent to the National Institute of Forensic Toxicology (NIFT). The samples were analysed using a standard program covering the most commonly abused drugs on the marked in Norway. BZDs, representing some of the most frequently detected drugs, were found in approximately 30% (n = 1051) of the cases, represented by 14% (n = 150) female and 86% (n = 901) male drivers. In 8% of the cases, one BZD only was detected, half of these cases with one BZD could reflect therapeutic use. One or more BZDs were combined with illegal drug(s) (73%), other prescribed drugs (10%), and/or alcohol (24%). 62% of the drivers with BZD detections, had earlier been arrested for the same offence, or six cases per rearrested driver. The frequency of earlier arrests were lower for female (34%) than for male (67%) drivers. Alcohol was most frequently found for those arrested for the first time before 1992, while BZD or illegal drugs were most frequently found for those with their first arrest during 1992-1995. Our study shows that apprehended drivers using BZD are mainly represented by drug abusers due to frequent multi-drug use, blood concentrations representing doses above therapeutic levels and high rearrest rate for the same offence. A treatment program or other reactions, are thus necessary in addition to fines, prison penalty and suspension of driving licence.     

GC／MS检验“敌杀死”和“赛丹”

目的利用色谱/质谱联用技术对“敌杀死”和“赛丹”两种农药原药进行分析。方法采用GC/MS联用方法。结果在“敌杀死”农药中检出了2种溴氰菊酯有效成分和2种杂质成分,在“赛丹”农药中也检出了2种硫丹有效成分,另外还检出了5种杂质成分。结论通过提出“敌杀死”和“赛丹”农药中其它成分来分析和确定农药种类,可为鉴定农药来源提供依据。     

Headspace/solid-phase microextraction/gas chromatography-mass spectrometry: a screening technique for the recovery and identification of volatile organic compounds (VOC's) in postmortem blood and viscera samples.

This paper describes the application of Headspace/Solid-Phase Microextraction/Gas Chromatography-Mass Spectrometry (HS/SPME/GC-MS) to the recovery and identification of volatile organic compounds in blood and viscera samples from deceased persons. The technique is used as a screening procedure to rapidly obtain information relating to toxicological investigations. The technique is suitable for the detection of volatiles (of wide boiling range) including butane, halothane, toluene, xylenes, and petrol residues in blood and viscera (lung, brain, and body fat).     

裂解气相色谱法检验静电复印墨粉

静电复印墨粉是复印文件检验的重要组成部分。本文通过电熨斗加热提取纸张上的墨粉,排除了纸张的平扰,用裂解气相色谱法对9个厂家共23个型号的墨粉进行检验。研究表明。该方法灵敏度高,分辨能力强,区分率可达到90.3％,是一种有效的检验方法。     

Separation of overlapping fingermarks by Matrix Assisted Laser Desorption Ionisation Mass Spectrometry Imaging

Latent fingermarks are impressions of the skin ridge pattern that are transferred by the accidental contact of fingertips with a deposition surface. The ability to enhance, lift and produce an image of a latent fingermark, for comparison and suspect match against a central fingerprint database, provides forensic investigators with what is still considered one of the most powerful means of biometric identification to date. Identification relies on the recovery, visualisation, extraction and comparison of local characteristics of the ridge pattern (minutiae) that are unique to individuals. Therefore, both for manual inspection of the minutiae and using automated ridge extraction algorithms, the clearer the ridge details, the more reliable and successful the match. Overlapping fingermarks pose a remarkable challenge in this context and are often encountered when developing marks from crime scenes. Here we propose the use of Matrix Assisted Laser Desorption Ionisation Mass Spectrometry Imaging (MALDI MSI) to separate overlapping fingermarks using ion signals that are characteristic of each fingermark and that may be endogenous or exogenous in nature. In this work we show that the methodology works in a number of different scenarios both using manual inspection of the spectrum profile or a much quicker multivariate statistical analysis.     

A validated method for the analysis of cannabinoids in post-mortem blood using liquid-liquid extraction and two-dimensional gas chromatography-mass spectrometry

Phenazepam is a long-acting benzodiazepine that, unlike other benzodiazepines, is currently not scheduled as a narcotic in Finland, most other European countries or the USA. It is used as an anxiolytic, sedative-hypnotic and anti-epileptic, mainly in Russia. In Finland, as well as in some other countries, an increase in the unauthorized use of phenazepam has been observed in recent years. In the one year period between July 1, 2010 and June 30, 2011 the prevalence of phenazepam in Finland was assessed among drivers apprehended for driving under the influence of drugs (DUID), in medico-legal autopsy cases and in police confiscations of illicit drugs. In DUID cases an LC-MS/MS method preceded by solid phase extraction was used for the determination of phenazepam. In the post-mortem investigations the sample preparation consisted of liquid-liquid extraction followed by derivatization and the determination was carried out by GC-MS. The police confiscations were analysed by GC-MS. There were 141 positive phenazepam cases among apprehended drivers, representing approximately 3.5% of all confirmed drug cases (n=4007) in this time period. The median (range) phenazepam blood concentration in DUID cases was 0.061 mg/L (0.004-3.600 mg/L). The median phenazepam concentration in cases with no concomitant stimulant use was significantly higher than the overall median concentration. Phenazepam was found in 17 medico-legal autopsy cases and the median (range) blood concentration was 0.048 mg/L (0.007-1.600 mg/L). Phenazepam was not considered by the medico-legal team to be the sole cause of death in any of the cases, the majority of them being accidental opiod overdoses. There were 26 seizures of phenazepam by the Police in the time period studied, some of the batches consisted of a mixture of phenazepam and stimulant designer drugs. The data show that phenazepam abuse is a widespread phenomenon in Finland. A typical user was a male multi-drug user in his 30s. The concentration range of phenazepam among apprehended drivers and medico-legal autopsy cases was wide and the drug was usually found along with other psychoactive drugs. Therefore, although it seems likely that phenazepam contributed to impairment of driving in some DUID cases, the extent of its effect remains unclear and further studies are needed to define the concentrations causing impairment and toxicity.