Fatal intoxications in Denmark following intake of morphine from opium poppies

In Denmark it is legal to grow opium poppies for the production of poppy seeds and until 1986 for decoration purposes, too. Danish poppy capsules contain 0.3-5 mg morphine per capsule and the content of morphine in opium exuded from the capsules may amount to 24%. This has resulted in misuse as both fresh and dried poppy capsules have been used for the production of "opium tea". During the period 1982-1985, seven casualties occurred among drug addicts in Denmark which were solely or partly caused by these opium poppies.     

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.     

Tamper-evident packaging requirements for over-the-counter human drug products--FDA. Final rule

The Food and Drug Administration (FDA) is amending its regulations on tamper-resistant packaging to require that all over-the-counter (OTC) human drug products marketed in two-piece, hard gelatin capsules be sealed using a tamper-evident technology; to change the term "tamper-resistant" in the labeling of all OTC drug products to "tamper-evident;" and to specify that the required OTC drug product labeling statement must refer to all packaging features used to comply with the tamper-evident packaging requirements, including those on the secondary package, the immediate container or closure, and any capsule sealing technologies used. FDA is taking this action as a result of its continuing review of the potential public health threat posed by product tampering and to improve consumer protection by addressing specific vulnerabilities in the OTC drug market.     

Measurement of kinetic energy dissipation with gelatine fissure formation with special reference to gelatine validation

Various methods for calculating the amount of kinetic energy dissipated by a bullet into ballistic gelatine have been suggested in literature. These methods were compared using the results of thirteen 9 mmx19 mm pistol and five 7.62 mmx 39 mm rifle bullets shot into 10% ballistic gelatine. The Wound Profile Method gave the highest correlation, 0.89, with the measured amounts of dissipated kinetic energy. The Fissure surface area and total crack length method gained 0.51 and 0.52, respectively. The experimental results were also compared with those from pig tests with the same bullet types. Using the z-test at 95% level of confidence no difference between impact velocity normalized bullet decelerations could be determined for the 9 mm bullet used. The same test showed significant difference for 7.62 mm bullets. That, however, can be considered to be the result of the bullet's tendency to tumble in non-homogenous living tissue causing significant dispersion of observed deceleration values. The results add further evidence supporting the validity of 10% gelatine at +4 degrees C as wound ballistic tissue simulant. The study also introduces the use of an elastic "shroud" to hold the gelatine in place, to some extent reduce the effects of asymmetric expansion of the gelatine and to simulate the expansion suppression effect of surrounding tissues.     

The affect of tissue depth variation on craniofacial reconstructions

The consumption of synthetic drugs, generally known as designer drugs, has increased drastically in all parts of the world. Typical constituents of designer synthetic drugs are chemical substances derived from amphetamine but significant differences in effects caused and duration may result. In May, 2005, the civil state police of Sao Paulo seized thirty-one gelatinous capsules containing a very small quantity of a white powder inside (approximately 1.5 mg per capsule). This paper describes the analytical assays that were used to identify the seized material. Preliminary assays using colorimetric tests and high performance thin-layer chromatography indicated that the capsules content could be an amphetamine derivative. In the capillary zone electrophoresis assay, it was possible to observe that the analyzed material had basic characteristics. Mass spectrometry analysis revealed that the compound had the same molecular mass as 2,5-dimethoxy-4-bromoamphetamine (DOB) and its identity was confirmed through collision-induced dissociation (CID) experiments. Finally, the comparison of infrared sample spectrum with a spectra library provided further evidence of the DOB presence in the seized material. Although a reference standard material was not available, the information gathered from the different assays allowed the conclusion that the substance was, in fact, DOB, a substance with a powerful hallucinogenic action of proscribed use in the country and which was seized and identified for the first time in Brazil.     

Simultaneous analysis of d-3-methoxy-17-methylmorphinan and l-3-methoxy-17-methylmorphinan by high pressure liquid chromatography equipped with PDA

d-3-Methoxy-17-methylmorphinan (Dextromethorphan, DXM), which is a structural analog of morphine and codeine, has been widely used as a non-narcotic antitussive agent. It is a safe drug in therapeutic dose and does not produce analgesic effects, while its enantiomer, l-3-methoxy-17-methylmorphinan called levomethorphan (LXM) is a potent narcotic analgesic. DXM has been widely abused in Korea due to its hallucinogenic effect in large doses; therefore, the health authorities have regulated its use as a psychotropic agent since 2003. As its abuse has been serious, a possibility that DXM would be smuggled into Korea has also increased. Moreover, it has been suspected that there was the possibility of the adulteration or substitution of DXM with LXM due to their chemical similarities. Therefore, it was necessary for us to establish the enantiomeric separation of DXM and LXM. In this study, a liquid chromatographic method using a chiral column capable of separating stereoisomers of DXM as well as analyzing the major metabolites of DXM, 3-methoxymorphinan, 3-hydroxymorphinan, and 17-hydroxymethylmorphinan was developed. The validation of a method was studied through repeatability of retention times. Using this method, 32 confiscated DXM samples were analyzed to identify the enantiomers of DXM. As a result, DXM was detected in all samples and there was no evidence of the adulteration or substitution of DXM with LXM. Nevertheless, the stereochemical analysis of DXM and LXM is important not only to identify starting materials for illegal drug manufacture but also to understand the trends of abused drugs.     

Preparing ballistic gelatine--review and proposal for a standard method

Meaningful assessment and comparisons on the injury potentials of various types of ammunition and credible forensic reconstruction require an agreement on standard tissue simulant. Gelatine blocks are relatively inexpensive and easy to produce and they meet most of the criteria for a good terminal ballistic simulant. This research looks into the variables of preparing ballistic gelatine and their effects on penetration resistance. It was found out that consistent quality gelatine blocks are easy to make and that the variables like water temperature have a far smaller effect than previously thought. Also water acidity variances allowed by European Council directive on drinking water do not have any measurable effect. A proposed standard method for gelatine preparation is presented together with penetration function for verification of gelatine quality.     

A comparison of penetration and damage caused by different types of arrowheads on loose and tight fit clothing

Bows and arrows are used more for recreation, sport and hunting in the Western world and tend not to be as popular a weapon as firearms or knives. Yet there are still injuries and fatalities caused by these low-velocity weapons due to their availability to the public and that a licence is not required to own them. This study aimed to highlight the penetration capabilities of aluminium arrows into soft tissue and bones in the presence of clothing. Further from that, how the type and fit of clothing as well as arrowhead type contribute to penetration capacity. In this study ballistic gelatine blocks (non-clothed and loose fit or tight fit clothed) were shot using a 24 lb weight draw recurve bow and aluminium arrows accompanied by four different arrowheads (bullet, judo, blunt and broadhead).The penetration capability of aluminium arrows was examined, and the depth of penetration was found to be dependent on the type of arrowhead used as well as by the type and fit or lack thereof of the clothing covering the block. Loose fit clothing reduced penetration with half of the samples, reducing penetration capacity by percentages between 0% and 98.33%, at a range of 10 m. While the remaining half of the samples covered with tight clothing led to reductions in penetration of between 14.06% and 94.12%.The damage to the clothing and the gelatine (puncturing, cutting and tearing) was affected by the shape of the arrowhead, with the least damaged caused by the blunt arrowheads and the most by the broadhead arrows. Clothing fibres were also at times found within the projectile tract within the gelatine showing potential for subsequent infection of an individual with an arrow wound.Ribs, femur bones and spinal columns encased in some of the gelatine blocks all showed varying levels of damage, with the most and obvious damage being exhibited by the ribs and spinal column.The information gleaned from the damage to clothing, gelatine blocks and bones could potentially be useful for forensic investigators, for example, when a body has been discovered with no weapons or gunshot residue present.     

Value of hair analysis in postmortem toxicology

It is generally accepted that chemical testing of biological fluids is the most objective means of diagnosis of drug use. The presence of a drug analyte in a biological specimen can be used to document exposure. The standard in postmortem drug testing is a general unknown screening, followed by the gas chromatographic/mass spectrometric confirmation conducted on a whole blood sample. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological specimens such as hair. The advantages of this sample over traditional media, like urine and blood, are obvious: collection is almost non-invasive, relatively easy to perform, and in forensic situations it may be achieved under close supervision of law enforcement officers to prevent adulteration or substitution. Moreover, the window of drug detection is dramatically extended to weeks, months or even years. The aim of this review is to document the current status of hair analysis in postmortem toxicology.     

Cause of death and drug use pattern in deceased drug addicts in Sweden, 2002-2003

Compared with their contemporaries, individuals abusing illicit drugs suffer a higher risk of premature death. In Sweden, a simple protocol for registration of fatalities among abusers of alcohol, pharmaceuticals, illicit drugs, or other substances, has been used by the forensic pathologists since 2001. This routine was introduced to allow for an evaluation of the cause and manner of death, and patterns of abuse among different groups of abusers. We explored the data on drug abusers (i.e. abusers of illicit drugs) subjected to a forensic autopsy 2002-2003. The Swedish forensic pathologists examined 10,273 dead victims during the study period and 7% (743/10,273) of the cases were classified as drug abusers. Toxicological analyses were carried out in 99% (736/743) and illicit drugs were detected in 70% (514/736) of these. On average, 3.8 substances (legal or illegal) were found per case. The most common substances were ethanol and morphine, detected in 43 and 35% of the cases, respectively. When exploring the importance of the different substances for the cause of death, we found that the detection of some substances, such as fentanyl and morphine, strongly indicated a poisoning, whereas certain other substances, such as benzodiazepines more often were incidental findings. In total, 50% (372/743) died of poisoning, whereas only 22% (161/743) died of natural causes. Death was considered to be directly or indirectly due to drug abuse in 47% (346/743), whereas evidence of drug abuse was an incidental finding in 21% (153/743) or based on case history alone in 33% (244/743). We believe that this strategy to prospectively categorize deaths among drug addicts constitutes a simple means of standardizing the surveillance of the death toll among drug addicts that could allow for comparisons over time and between countries.     

DNA on drugs

The use of illicit drugs is a continuing blight on society. Detecting DNA from individuals involved in the manufacturing and distribution of drugs can provide valuable investigative information or strategic intelligence which, in turn, can be used to disrupt the supply and distribution of illicit drugs. Our study details the transfer, persistence, prevalence, and recovery of human DNA on the exterior of tablets and capsules, as well as within drug powders. Various experiments were conducted to mimic stages in the creation and packaging of tablets and capsules. We showed that the act of brief contact (1–3 s) is sufficient to generate informative DNA profiles that can be uploaded and compared to databases internationally. This work complements chemical drug profiling data by linking seizures to each other and individuals via DNA profiles, providing information to prosecution or intelligence agencies. The generation of DNA information from illicit drug preparations is another tool that can be used in the fight against illicit drug manufacture and distribution.     

Spatially offset Raman spectroscopy (SORS) for the analysis and detection of packaged pharmaceuticals and concealed drugs

Spatially offset Raman spectroscopy (SORS) is a powerful new technique for the non-invasive detection and identification of concealed substances and drugs. Here, we demonstrate the SORS technique in several scenarios that are relevant to customs screening, postal screening, drug detection and forensics applications. The examples include analysis of a multi-layered postal package to identify a concealed substance; identification of an antibiotic capsule inside its plastic blister pack; analysis of an envelope containing a powder; and identification of a drug dissolved in a clear solvent, contained in a non-transparent plastic bottle. As well as providing practical examples of SORS, the results highlight several considerations regarding the use of SORS in the field, including the advantages of different analysis geometries and the ability to tailor instrument parameters and optics to suit different types of packages and samples. We also discuss the features and benefits of SORS in relation to existing Raman techniques, including confocal microscopy, wide area illumination and the conventional backscattered Raman spectroscopy. The results will contribute to the recognition of SORS as a promising method for the rapid, chemically specific analysis and detection of drugs and pharmaceuticals.     

Capillary ion electrophoresis of endogenous anions and anionic adulterants in human urine

Normal human urine contains many anions and cations. Ionic concentrations in urine have classically been determined by spectrophotometry of color reactions, flame emission spectrophotometry, atomic absorption spectrophotometry, high performance liquid chromatography, or potentiometry with ion-specific electrodes. Capillary ion electrophoresis (CIE) is a form of capillary electrophoresis which uses the differential electrophoretic mobility of ions to perform a separation of an ionic mixture. Various salts can be added to urine specimens to abnormally elevate ionic concentrations and interfere with either immunoassay urine drug screening procedures or gas chromatographic/mass spectrometric confirmation techniques. Application of CIE for the direct detection of endogenous anions and anionic adulterants in human urine specimens was the purpose of this investigation. CIE was performed using a Waters Quanta 4000 Capillary Electrophoresis System with either direct or indirect ultraviolet absorption detection at 254 nm. CIE of 30 random normal urine specimens and 21 urine specimens suspected of adulteration was performed. Duplicate aliquots were assayed by CIE and by colorimetric technique for nitrite. Sixteen specimens had elevated concentrations of nitrite and/or nitrate. The correlation coefficient between nitrite CIE and colorimetric results was 0.9895. Three specimens had detectable concentrations of chromate and were suspected of being adulterated with "Urine Luck," an adulterant found to contain chromate. Two specimens suspected of being adulterated with bleach were found to only contain chloride, sulfate, and phosphate. CIE is applicable to forensic analysis of urine anion concentrations. CIE can easily quantitate numerous endogenous anions and offers a method to detect and/or confirm anion adulteration of urine specimens.     

Analysis of illicit dietary supplements sold in the Italian market: Identification of a sildenafil thioderivative as adulterant using UPLC–TOF/MS and GC/MS

Identification of pharmaceutical active ingredients sildenafil and tadalafil and the characterization of a dimethylated thio-derivative of sildenafil, called thioaildenafil or thiodimethylsildenafil, in illicit dietary supplements were described.A multi-residual ultra-performance liquid chromatography–time of flight mass spectrometry (UPLC–TOF/MS) method was developed to screen for the presence of the phosphodiesterase-5 (PDE-5) inhibitors sildenafil, tadalafil, and vardenafil and their analogues thioaildenafil and thiohomosildenafil in powders and pharmaceutical dosage forms. The study was developed in connection with an operation supervised by the Italian Medicines Agency (A.I.F.A.), aimed to monitor dietary supplements in the Italian market. In two of the eleven specimens under investigation, high-resolution mass spectrometry (HR-MS) allowed the identification of the PDE-5 inhibitors sildenafil and tadalafil, while another specimen proved to contain a unapproved dimethylated thioderivative of sildenafil, thioaildenafil or thiodimethylsildenafil, identified for the first time in Italy as adulterant in food supplements.     

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.     

Creatinine analysis in single collection urine specimens.

Controlled and uncontrolled fluid intake studies were conducted on series of volunteers over the 6 or 12 h of the study periods. Urine specimens were obtained from each subject randomly or at specified times relative to fluid ingestion. Creatinine analysis performed by a modification of the Abbott TDx procedure demonstrates that the values obtained from single collection specimens fall almost in the same range as the values from 24 h pooled collection specimens. The creatinine concentration can be used to indicate possible adulteration of urine specimens by dilution as a means of avoiding detection of use of drugs of abuse. Between 4 and 7 h are required for a decrease in creatinine concentration to about 100 mg/dL from an initial mean of about 170 mg/dL. A minimum of 6 h is needed for any creatinine value to fall to 50 mg/dL or less. Thus, it appears that creatinine output is sensitive to the amount of fluid ingested, but the relationship is neither linear nor immediate. The absence of a significant creatinine concentration in a specimen can be used as an indication of direct or indirect adulteration of the urine specimen by dilution or replacement with water. At NDSL-Great Lakes, a decline of the creatinine concentration to 30 mg/dL is used as a cutoff for differentiating between urine specimens that might have been tampered with to avoid detection of drug use and those specimens that are dilute for other reasons. Values at 10 mg/dL or less are suggestive of replacement by water. The information is provided to local commands for investigation prior to initiation of punitive action by the command.     

Recovery of Latent Fingerprints and DNA on Human Skin*

Abstract: The project “Latent Fingerprints and DNA on Human Skin” was the first systematic research in Europe dealing with detection of fingerprints and DNA left by offenders on the skin of corpses. One thousand samples gave results that allow general statements on the materials and methods used. The tests were carried out according to a uniform trial structure. Fingerprints were deposited by natural donors on corpses. The latent fingerprints were treated with magnetic powder or black fingerprint powder. Afterward, they were lifted with silicone casting material (Isomark^®) or gelatine foil. All lifts were swabbed to recover DNA. It was possible to visualize comparable and identifiable fingerprints on the skin of corpses (16%). In the same categories, magnetic powder (18.4%) yielded better results than black fingerprint powder (13.6%). The number of comparable and identifiable fingerprints decreased on the lifts (12.7%). Isomark^® (14.9%) was the better lifting material in comparison with gelatine foil (10.1%). In one‐third of the samples, DNA could be extracted from the powdered and lifted latents. Black fingerprint powder delivered the better result with a rate of 2.2% for full DNA profiles and profiles useful for exclusion in comparison with 1.8% for the magnetic powder traces. Isomark^® (3.1%) yielded better results than gelatine foil (0.6%).     

Prodrugs of New Psychoactive Substances (NPS): A New Challenge

The concept of a substance acting as a prodrug for an intended drug is not new and has been known and utilized with particular benefits within medicine for efficacy and patient safety. Prodrugs of psychoactive substances are also not particularly new but this has also extended to considerations of prodrugs of new psychoactive substances (NPS). The continuing evolution of NPS has been a constant forensic challenge. In some countries, this constant evolution has led to the introduction of various alternative methods of drug control. Whether for this reason or in the pursuit of user experimentation, prodrugs of NPS have been discussed, developed, and exploited, posing some distinct forensic challenges. This is especially the case within toxicological analysis of biological fluids and for some substances, also forensic chemical analysis, through inherent instability of the prodrug or metabolism in the body. Particular examples of NPS prodrugs include 1-propanoyl-LSD, 1-butanoyl-LSD, 1-acetyl-LSD, and 2C-B-AN. This is in addition to associated substances and medicines that may be used for an intended pharmacological effect. Various prodrugs for stimulant and hallucinogenic substances in particular have appeared in the literature and have been discussed within drug user forums and made available for purchase online. Presently, drug monitoring data from national and international systems indicate that prodrugs are not widely available or problematic. Nevertheless, it is important that there is sufficient awareness of the prodrug concept and potential impact and associated forensic implications, not just for chemical analysis but also for toxicological considerations when a substance has been used.     

Morphometric diagnostics of the age of encapsulated subdural hematomas

The present morphometric investigation was carried out using dura matter preparations, capsules, and contents of 94 encapsulated subdural hematomas obtained from the corpses of subjects with a non-penetrating craniocerebral injury and the duration of the post-traumatic period ranging from 8 days to 2.5 years. The correlation analysis confirmed the necessity of differentiation between resorbed and unresorbed encapsulated subdural hematomas. The data obtained were used to construct 5 regression models for the estimation of the age of unresorbed encapsulated subdural hematomas and 1 regression model for the identification of the age of resorbed encapsulated subdural hematomas. The regression models included different combinations of three morphometric characteristics of the hematoma capsule as the independent variables, viz. maximum thickness, relative extent of hemosiderosis, and relative amount of macrophages in the cellular infiltrate. The amount of variability in the age of encapsulated subdural hematomas accounted for by the regression models is 62%. It is concluded that the results of the study can be used in the practical work of forensic medical experts.