Toxicological results in a fatal and two non-fatal cases of scopolamine-facilitated robberies.

The use of scopolamine as an incapacitating drug, in sexual crimes and robberies, has been known for many decades. However, blood concentrations and doses of scopolamine in those cases are largely unknown. Here we present the toxicological results of one fatal and two non-fatal cases in a series of scopolamine-facilitated robberies. In the fatal case, the concentration of scopolamine in heart blood was 0.30mg/L, about 3000 times higher than the average therapeutic level of 0.0001mg/L (for one dermal patch). In femoral blood, the concentration of scopolamine was much lower (0.0048mg/L), but still 50 times higher than therapeutic levels. The scopolamine concentration in the stomach was very high (20mg/kg) as compared to the heart blood and femoral blood, which explains the very high concentration in heart blood by postmortem leakage from the stomach. In the non-fatal case, the scopolamine concentration in serum, obtained 23h after the incident, was 0.00035mg/L. The estimated concentration of scopolamine at the time of the incident is 0.0035mg/L. In the other non-fatal case, scopolamine was detected in urine and in hair.

Hair as a biological specimen for therapeutic drug monitoring.

To study the potential of hair as a biological specimen in therapeutic drug monitoring (TDM), a review of the correlation between hair concentration, blood levels, dose and therapeutic effects of various drugs is presented. The results indicate there is a fair correlation between plasma and hair for several medicines. Moreover, hair samples have the advantage of providing information of more prolonged drug intake, thus allowing a better evaluation of patient compliance. Using segmental hair analysis, only a single sample is necessary. We conclude that hair has potential as a biological specimen in TDM--at least as far as compliance is concerned and possibly as a longer term record of drug concentrations--and that correlation between hair concentration, blood levels and clinical efficacy should be investigated for all drugs where TDM is indicated.

Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market.

1-Aryl-piperazine compounds are, depending on their substituents, selective for certain serotonin receptors and together with their easy availability and their so-called legal status, this group of psychoactive compounds are potential designer drugs-of-abuse. Internet in that respect is an important source of information and distribution facilities. Because this development may have consequences for the interpretation of future clinical and forensic toxicological case studies, some analytical aspects of 1-benzyl-piperazine (BZP), 1-[4-methoxyphenyl]-piperazine (pMeOPP) and 1-[3-trifluoromethylphenyl]-piperazine (TFMPP) were studied. BZP was not detected by the AxSYM FPIA technology designed to determine amphetamine-like compounds, but had showed some cross reactivity with EMIT d.a.u.. The cross reactivities at 300 and 12,000ng/ml (RS)-amphetamine equivalents were 0.4 and 1.3%, respectively. Although BZP was not identified directly by the REMEDi HS Drug Profiling System, it can be detected by this HPLC/UV scanning system. Using GC/NPD without derivatisation, BZP, pMeOPP and TFMPP can be analysed for and applying GC/MS without or with acetylation or trifluoroacetylation, these compounds can be identified unambiguously. The usefulness of GC/NPD and GC/MS in this respect was demonstrated by the quantitative and qualitative analysis of the content of a capsule with the synthetic stimulant A2, which proved to contain 86.4mg of BZP.

Heroin self-administration by means of 'chasing the dragon': pharmacodynamics and bioavailability of inhaled heroin.

In this controlled clinical study, the bioavailability and pharmacodynamics of inhaled heroin are evaluated and compared between 'chasing the dragon' and inhalation from a heating device, and at three dose levels, 25, 50 and 100 mg heroin, in two separate study phases. In study phase 1, no differences between the inhalation methods were detected on any of the physiological or behavioral measures, nor in bioavailability. Subjectively, the participants had a strong preference for the method of chasing, which was therefore used in study phase 2. In phase 2, heroin produced a dose-related increase in subjective drug-liking, body temperature and heart rate, and a clear, dose-related decline in reaction time. Linearly dose-related differences were found in the amount of total morphine in urine, amounting to an average of 45% of the parent heroin base received. Based on these findings, it is concluded that chasing is quite an effective route of heroin administration, producing rapid, dose-related subjective and objective effects and a sufficiently high and reproducible bioavailability.

Evaluation of a novel diffusion cell for in vitro transdermal permeation: effects of injection height, volume and temperature.

The objective of this study was to evaluate the performance of a new, compact, dynamic diffusion cell for in vitro transdermal permeation. These so-called Kelder-cells were developed as an automated alternative to the static Franz diffusion cells. The new cells were used in combination with the ASPEC-system (automatic sample preparation with extraction columns) which was initially designed for the automation of solid-phase extractions. Three variables were tested to optimize the performance of the new cell system: injection height into the inlet compartment, volume flowing through the receptor compartment and temperature. Experiments were performed using the tritium labelled anticholinergic [3H]dexetimide permeating through an artificial membrane (Silastic). The injection height of the needle into the inlet compartment of the cell should be programmed at -34 mm to ensure complete air tightness, thus forcing the buffer to flow through the cell. The volume of buffer flow through the receptor compartment is important in maintaining sink conditions: a volume of 117 microliters was chosen to replace the total content of the cell (84 microliters) every 2 min. The temperature was precisely controlled in a thermostatic cabinet to minimize variations in experimental conditions. For [3H]dexetimide, an increase in temperature of 20 degrees C reduced the lag time by a factor of approximately two, however the influence on the flux was negligible. The data for the Kelder-cells were comparable with static Franz diffusion cells at a pseudo-steady state, however Kelder-cells have the advantage of automatic sampling, continuous replacement of the receptor solution, and unattended operation over at least 24 h.

Novel diffusion cell for in vitro transdermal permeation, compatible with automated dynamic sampling.

The development of a new diffusion cell for in vitro transdermal permeation is described. The so-called Kelder cells were used in combination with the ASPEC system (Automatic Sample Preparation with Extraction Columns), which is designed for the automation of solid-extractions (SPE). Instead of SPE columns, 20 Kelder cells were placed in the racks. This allowed automatic sampling of up to 20 cells for 24 h in a dynamic mode. The cells consist of an inlet compartment, a donor compartment and a receptor compartment. The size and the depth of the inlet compartment were important to avoid entrapment of air bubbles in the receptor compartment. The Kelder cells mimic blood flow beneath the skin by replacement of the permeating drug every 2 min. Hence sink condition are more easily maintained than with the static Franz diffusion cell. The performance of the cells was tested with permeation experiments using atropine as a model drug permeating through an artificial membrane (Silastic). The use of this skin model minimized the variability in permeation of atropine as compared with human skin.

Application of radioreceptor assays for systematic toxicological analysis--1. Procedures for radioreceptor assays for antihistaminics, anticholinergics and benzodiazepines.

Radioreceptor assays can be a useful tool for systematic toxicological analysis in that they can be applied for the detection of an entire pharmacological class of drugs. In the present paper procedures for radioreceptor assays for benzodiazepines, anticholinergics and antihistaminics have been described in detail. The development of the assay for antihistaminics in urine is given in order to illustrate the prerequisites for these types of assays with regard to the incubation conditions. In part 2 the applicability of the three assays for systematic toxicological analysis will be evaluated on the basis of testing a large number of urine samples after administration of a selected number of drugs to healthy volunteers and patients.

Application of radioreceptor assays for systematic toxicological analysis--2. Theoretical considerations and evaluation.

In this paper the applicability of radioreceptor assays for systematic toxicological analysis will be evaluated on a theoretical basis as well as on the basis of the outcomes of the analysis of a large number of urine samples collected after administration of a selected number of drugs to healthy volunteers and patients. Many drugs and other substances of toxicological relevance exert their action through an interaction with one or more receptor (sub)types. Whether the number of persons are using particular drugs intentionally or unintentionally, radioreceptor assays can be a useful tool for systematic toxicological analysis in that they can be applied to the identification of entire pharmacological classes of substances as well as pharmacologically active metabolites. In part 1 of this paper detailed procedures for radioreceptor assays for benzodiazepines, anticholinergics and antihistaminics have been described in detail in order to illustrate not only the potentials but also the limitations of assay conditions. Fifteen drugs were administered to patients and volunteers and urine samples were collected and determined with the three radioreceptor assays. The results of this study underline the theoretical applicability of receptor assays in systematic toxicological analysis though sample pretreatment procedures may contribute to an improvement in sensitivity and applicability to other biofluids.