Rapid detection and speciation of illicit drugs via a thin-film microextraction approach for wastewater-based epidemiology study.

High detection frequency of illicit drugs in water samples urges the development of rapid detection method for wastewater-based epidemiology (WBE) study. Here, we first developed a fast, convenient, and cost-effective method by combining thin-film microextraction (TFME) with gas chromatography-mass spectrometry (GC-MS) for sensing illicit drugs in wastewater sample. A divinylbenzene particle-loaded membrane was prepared by dip coating on a copper mesh. The sampling conditions of three illicit drugs were optimized and the performance of the proposed method was evaluated. The limit of detection was 5.5 2.0, and 1.1 ng L-1 for methamphetamine (MAMP), ketamine (KET), and methaqualone (MEQA), respectively, with acceptable precision (< 6.1 % for membrane to membrane reproducibility) and recovery from influent water (95 % - 111 %). Then, the proposed method was applied to study the occurrence and distribution of the target compounds in a wastewater treatment plant. The presence of methamphetamine, ketamine, and methaqualone was confirmed and their concentrations in the influent sample were 57 ± 8, 40 ± 4, and 75 ± 2 ng L-1, respectively. The speciation of the target compounds in different ponds was also investigated. Results showed that the content of organic matter and the pH of the sample significantly affected the binding state of the compounds. This work provides an efficient and accurate analytical protocol for WBE investigation of illicit drugs.

Toxicología de las drogas de síntesis / Synthetic illicit drugs toxicology

Las drogas de síntesis o 'drogas de diseño' son sustancias psicoactivas de uso recreacional que se fabrican en laboratorios clandestinos. La producción, variedad y número de consumidores de estas drogas aumentan cada año en toda Europa, y con ellos los problemas sanitarios derivados de su uso. Estos problemas comprenden tanto sus efectos secundarios o la intoxicación aguda como sus aún no del todo conocidas repercusiones orgánicas a largo plazo, así como la toxicidad de las sustancias de corte, la de los productos residuales originados en la fabricación de la propia droga y su uso combinado con el de otras drogas. Dentro de la denominación de drogas de síntesis se diferencian principalmente cuatro grupos de sustancias muy diferentes: los derivados anfetamínicos, los opioides sintéticos, las arilhexilaminas y los derivados de la metacualona. Esta revisión aporta una descripción sistemática de dichos compuestos y de su efectos físicos y psíquicos. (AU)

Toxicological screening for drugs of abuse in samples adulterated with household chemicals.

OBJECTIVES: Urine samples that tested positive for two drugs of abuse, namely cannabis and methaqualone, were reassayed in the presence or absence of common household chemicals: Jik (sodium hypochlorite), Dettol (chloroxylenol), G-cide Plus (glutaraldehyde), Perle Hand Soap, ethanol, isopropanol and peroxide (20 volumes). These chemicals are frequently used for the adulteration of urine samples. SETTING: Department of Pharmacology, University of Stellenbosch. METHODS: Household chemicals, at three different concentrations, were added to urine samples that tested positive for methaqualone and cannabis. Samples were reanalysed on an ETS Plus Analyser (Syva Company, San Jose, Ca.) using Emit drugs-of-abuse urine test reagents. RESULTS: Most of the chemicals tested influenced the outcome of positive toxicological screening results for these drugs. G-cide (glutaraldehyde) and Perle Hand Soap had the largest effect (false-negative) on the methaqualone test. Dettol (chloroxylenol) and Perle Hand Soap had the largest effect on the cannabis test. Higher concentrations of the adulterant were not always an indication of the extent of modification of the test result. The addition of certain chemicals (ethanol, isopropanol and peroxide) to the urine samples tested for methaqualone interfered with the test to such an extent that it gave invalid test results.

Analysis of methaqualone in biological matrices by micellar electrokinetic capillary chromatography. Comparison with gas chromatography-mass spectrometry.

The analysis of methaqualone (MTQ) in biological matrices by capillary electrophoresis (CE) is described. This methods uses liquid-liquid extraction and micellar electrokinetic capillary chromatography (MECC), an operation mode of CE. Separations are made using a 25 cm long capillary and a borate/phosphate buffer at pH 8.2. Using gas chromatography with mass spectrometry detection (GC-MS) as reference method, MTQ has been analyzed in urine, blood, gastric content and hair. For hair analysis, supercritical fluid extraction was compared with liquid-liquid extraction. Linearity was established in urine and blood between 0.25 and 10.0 micrograms/ml. MTQ recovery from blood was estimated at 60%. The limit of detection of this method in urine is about 0.10 microgram/ml. Drawbacks and advantages of MECC over GC-MS are discussed.

Shift of the high-performance liquid chromatographic retention times of metabolites in relation to the original drug on an RP8 column with acidic mobile phase.

The effect of the structural change in the metabolization of drugs on the HPLC retention time with an RP8 column with an acetonitrile-phosphate buffer (pH 2.3) as the mobile phase was investigated at model compound pairs of 29 functionalization reactions. A more or less typical region for T(M)=log(k'M/k'D) was found for each of these reactions (with k'M and k'D being the capacity factors of the metabolite and the drug, respectively), which can be explained by an increase or a decrease of the hydrophilic properties caused by the structural change. This effect is superimposed by an essential influence of the unchanged part of the molecule and in some cases by special intramolecular interactions like the hydrogen bond. Despite the more complicated structure of real drugs the results obtained at the model compound pairs were confirmed for most of the 55 metabolite/drug pairs. The practical use of the T(M) values as a support to distinguish between different metabolites in the HPLC-DAD analysis of intoxications is demonstrated with cases of poisoning with diphenhydramine, propafenone and methaqualone.

A case of lethal intoxication after ingestion of toquilone compositum.

A case of acute intoxication of both methaqualone and diphenhydramine is reported. The analysis of these compounds was performed by liquid-liquid extraction (Toxi-Lab DPC procedure) followed by gas chromatography/mass spectrometry determination; both substances are contained in the pharmaceutical formulation called Toquilone Compositum (Medichemie, Switzerland).

Determination of methaqualone and its metabolites in urine and blood by UV, GC/FID and GC/MS.

A systematic procedure for the determination of methaqualone and its metabolites in blood and urine by UV spectrophotometry, GC and GC/MS was developed. Urine and blood samples were from a suicidal patient who ingested 18 tablets of methaqualone. Both solid phase and liquid-liquid extractions were used in the extraction and clean-up of the samples. The total amount of methaqualone and its metabolites was measured by UV spectrophotometry. The amount of parent methaqualone was quantitated by GC/FID. Methaqualone and its 10 metabolites including two acetyl metabolites were found in urine and blood. This procedure is useful for monitoring drugs in emergency treatment.

Simultaneous sequential determination of compounds of toxicological interest in mixtures by derivative spectroscopy.

An absorption spectroscopic method was developed for the sequential determination of mixture components. The proposed method is straightforward and convenient and provides optimal results that increase the potential of spectrophotometric techniques as applied to date. The method was applied to the sequential resolution of mixtures of pure components of toxicological interest yielding close UV absorption bands by using derivative spectroscopy.

An evaluation of the results of a drug sample analysis.

An analysis of drug samples received by the National Toxicology Institute at Madrid during the period from September 1985 to May 1987 was undertaken with a view to carrying out an epidemiological assessment of drug abuse. Of 414 street drug samples, 63.5 per cent contained heroin, 12.5 per cent cocaine, 8.5 per cent amphetamine and 15.4 per cent other substances. The concentration of heroin ranged from 21 to 60 per cent in most of the samples (91.8 per cent) that contained it. Similar concentrations of cocaine were found in the samples containing that substance. Adulterants were detected in 78.8 per cent of the samples containing heroin, 59.6 per cent of the samples containing cocaine and 56 per cent of the samples containing amphetamine. The most common adulterants in the samples containing heroin were caffeine (68.4 per cent), phenobarbital (19.7 per cent), methaqualone (13.4 per cent) and procaine (13.4 per cent), while lidocaine was the most common adulterant (52 per cent) in the samples containing cocaine.

[In vitro and in vivo photochemical reactivity of methaqualone-1-oxide]. / In-vitro- und in-vivo-Untersuchungen zur fotochemischen Reaktivität von Methaqualon-1-oxid.

Methaqualone-1-oxide (1) exhibits photochemical reactivity. By irradiation of 1 with solar light the oxaziridin 3 is formed at first, which reacts in vitro (human proteins) and in vivo (rats) with macromolecules. As result of the photochemical in vitro and in vivo reactions of 1 the photoproduct 2-acetamidobenzoic acid-2'-methylanilide (6), involved in oxidation of protic compounds, was detected and after hydrolysis of proteins it appears that the short-lived 3 was adding to proteins.

[Use of spectral methods in the study of poisoning]. / Príspevek k pouzití nekterých spektrálních metod pri výsetrování intoxikací.

The authors demonstrate on selected cases from routine practice the possibility of rational and effective use of spectral methods in the examination of intoxications. They discuss the use of ultraviolet and infrared spectroscopy, in particular their combination with chromatographic methods (chromatography on a thin layer, gas chromatography).

Analysis of drug involvement in traffic fatalities in Alabama.

Toxicology studies were performed on a subset of highway fatalities in Alabama. Results of those tests were analyzed for the years 1980 through 1984. It was found that 63% of driver fatalities tested had some level of blood alcohol concentration. From a smaller subset of the fatalities, it was found that almost 17% tested positively for marijuana. More than 5% of fatalities had some level of drugs (either illicit or prescription) in their blood stream. A statistical significant association was found between diazepam (tranquilizer) and low alcohol blood concentration. Another important finding is that for Alabama, marijuana is a problem drug of young drivers.

[Photochemical reactivity of methaqualone-1-oxide]. / Fotochemische Reaktivität von Methaqualon-1-oxid.

The photoreactivity of methaqualone-1-oxide a main metabolite of the hypnotic methaqualone has been studied in polar and apolar solvents using UV- and daylight. Five photoproducts were isolated and identified by their analytical behaviour (TLC, UV, IR, high-resolution MS). The structure of the compounds 4, 6, 7, and 8 refer to unstable, reactive intermediates (oxaziridine, biradical) during the photolysis.

Performance characteristics of methods of analysis used for regulatory purposes. I. Drug dosage forms. B. Gas chromatographic methods.

Gas chromatographic methods for the analysis of drug dosage forms consist of a simple extraction, dilution with an internal standard solution, and injection, or, even simpler, dilution with the internal standard solution and injection. These methods were used in 7 collaborative studies of the determination of 12 pharmaceuticals, published in the Journal of the AOAC during 1973-1983. A total of 43 individual materials consisting of various dosage forms were each analyzed, usually in duplicate, by an average of 8 laboratories, with a total of 582 reported determinations. The average within-laboratory coefficient of variation (CVo) was 1.25% and the average among-laboratories coefficient of variation (CVx) was 2.41%, for a CVo/CVx ratio of 0.52, at an average outlier rate of 1.4% of the reported values. The line of best fit for CVx plotted against concentration increases with decreasing concentration, extending from a CVx of approximately 1.8% at 100% concentration to a CVx of approximately 3.2% at 1% concentration. The change in CVx for a 10-fold decrease in concentration is approximately 0.7% CVx, independent of analyte and matrix.

Gas chromatographic screening for drugs and metabolites in plasma and urine.

There is an increasing need for sensitive and specific methods for toxicological screening. Development of a dual-column gas chromatography system for the screening of drugs and metabolites in the plasma of poisoned patients is described. The system has been evaluated using plasma from a well-documented series of patients presenting with overdose, and results obtained have been compared with results of specific assays for the groups of drugs encountered. The method has been found to be of value in the treatment of poisoned patients despite its apparent insensitivity to certain more polar drug metabolites such as nortriptyline and desmethyldiazepam.

Monitoring saliva concentrations of methaqualone, codeine, secobarbital, diphenhydramine and diazepam after single oral doses.

A preliminary investigation was undertaken to determine the feasibility of monitoring saliva levels of drugs for forensic purposes. Single oral doses of the title compounds were administered to healthy volunteers. Plasma and saliva levels were measured and ratios calculated for all drugs except diazepam. Saliva/plasma ratios for methaqualone, diphenhydramine and secobarbital were all less than one and reasonably consistent between collection times and subjects. The saliva/plasma ratios for codeine were more variable, but always greater than one. Although more detailed investigation is necessary, saliva may be a useful medium for forensic monitoring of drug ingestion.