[Detection of drugs of abuse].
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Gas Chromatography-Mass Spectrometry↗
Biomedical subjects
L von Meyer
Publications and source records attributed to L von Meyer.
Determination of lysergic acid diethylamide in body fluids by high-performance liquid chromatography and fluorescence detection--a more sensitive method suitable for routine use.
A new method for determination of lysergic acid diethylamide (LSD) in body fluids by high-performance liquid chromatography and fluorescence detection was developed based on previously published methods. The new method is suitable for confirmation of samples tested positive by immunoassay, avoiding loss of LSD by absorption to surfaces. The reduced loss of LSD results in improved sensitivity. This is achieved by adding ethylene glycol to the samples, which cover glass surfaces. This principle can similarly be used to improve analysis of other drugs. Body fluids for analysis included urine and whole blood. An internal standard was applied for quantification of LSD. The new method offers satisfying precision data and has a detection limit of less than 0.05 ng/nL.
Body Fluids↗
European multicentre evaluation of the analytical performance of the Abbott AxSYM Abused Drugs Assays.
In accordance with the guidelines of the European Committee for Clinical Laboratory Standards (ECCLS), the performance of the Abbott AxSYM Abused Drugs assays were evaluated and compared with the results provided by the following systems: Syva Emit d.a.u./Roche Cobas Mira S Plus, Abbott TDx and ADx, Syva Emit d.a.u./Syva ETS Plus, Syva Emit II/Hitachi 717 and Roche Abuscreen OnLine/Roche Cobas Mira S Plus. The test analytes, cannabinoids, cocaine metabolites, opiates, benzodiazepines and barbiturates, were each investigated in three laboratories on different systems. The imprecision of all systems in the series and from day to day was good, with CVs less than 5% or 10%, respectively. The AxSYM calibration curves were stable for 3-4 months and none of the systems displayed any shift in the results of the analyses within one day or any faults caused by sample contamination. Within the framework of this study, a total of 1860 urine samples were investigated; 741 results were positive. All results which remained discrepant between AxSYM and the comparison systems after repeated analysis (n = 17) were subjected to further investigation using a reference method, with the exception of one barbiturate and two benzodiazepine samples. An additional test criterion was the practicability of the systems investigated and the versatility of the software. During this evaluation, the results provided by the Abbott AxSYM were excellent and were fully in line with the manufacturer's claims. The reliability of the FPIA technology that has been the subject of frequent investigation was also convincing during this evaluation. The possibility of semi-quantitative determination, the stability of the calibration curves, the ability to process an emergency sample without delay and its high suitability to routine operations are the convincing benefits offered by this system.
Calibration↗
Nonoxidative ethanol and methanol changes in the heart and brain tissue of alcohol abusers.
Fatty acid ethylesters (FAEE) are synthesized from ethanol and fatty acids in the heart and brain. Similarly fatty acid methylesters (FAME) are synthesized from methanol and fatty acids. Whereas methanol reportedly indicates recent or chronic consumption of alcoholic beverages, an elevated serum methanol concentration (SMC) indicates mainly chronic alcohol intake. We compared levels of FAEE and FAME in cardiac and brain tissues with the blood ethanol concentration(BEC) and SMC in 18 alcohol abusers and 29 control subjects without history of alcohol abuse(control) to clarify the relationships between BEC and FAEE levels and that between SMC and FAME levels. We also assessed the possibilities of discriminating the alcohol abusers from the control group and of detecting FAEE and FAME accumulations in cardiac and brain tissues. Levels of FAEE and FAME were determined by gas chromatography (GC) in autopsied cardiac and brain tissues. Heart FAEE (HFAEE) levels correlated with BEC (r = 0.61) and it was possible to distinguish between alcohol abusers and controls using discriminant analysis. HFAEE levels in the alcohol abusing group were elevated even with low BEC. Therefore, HFAEE levels indicate ethanol accumulation in cardiac tissues of alcohol abusers. Brain FAEE (BFAEE) and heart and brain FAME (HFAME and BFAME) levels did not correlated closely with BEC and SMC, respectively. However, there are some possible means of discriminating between the two groups in terms of BEC and BFAEE, and SMC and FAME respectively, using discriminant analysis. Employing this analysis, the rate of misclassification was 17-25.5%. The mean levels of HFAEE, BFAEE, HFAME and BFAME were higher in the alcohol abusing group than in the control group, even when their BEC and SMC were quite low.
Acyltransferases↗
Evaluation of a solid-phase extraction procedure for the simultaneous determination of morphine, 6-monoacetylmorphine, codeine and dihydrocodeine in plasma and whole blood by GC/MS.
Different procedures of solid-phase extraction were re-examined and a new solid-phase extraction procedure was developed using gas chromatography-mass spectrometry for the simultaneous detection and quantitation of morphine, 6-monoacetylmorphine, codeine and dihydrocodeine in plasma and whole blood. The effects of different types of sorbent and buffer solutions on the recoveries and purity of the extracts were also studied. Some preparation techniques on whole blood samples were also investigated. The method developed using Chromabond C18 (100) with spiked plasma samples had good recoveries for all opiates of interest: morphine 93.1% +/- 7.4%, 6-monoacetylmorphine 68.0% +/- 6.7%, codeine 77.0% +/- 8.3% and dihydrocodeine 67.9% +/- 8.4%. The detection limit of all compounds was less than 5 micrograms/L. The blank plasma showed no interfering peaks in the GC/MS-analysis.
Autopsy↗
Carboxyhemoglobin blood concentrations in suicides by fire.
A total of 21 suicides by fire (16 males and 5 females) were investigated. In at least 18 of the 21 cases, flammable liquids were used as accelerants leading to severe and extensive burns. The determination of carboxyhemoglobin concentrations revealed comparatively low levels of between 3 and 30 per cent in suicides committed in the open whereas four out of five deceased found dead in gutted cars showed carbon monoxide saturations ranging from 34 to 87 per cent. In 18 cases (86%) soot was detectable in the airways even in cases with slightly elevated carboxyhemoglobin concentrations, indicating the importance of a careful examination of the airways at autopsy for the detection of vital signs.
Adult↗
Influence of halothane on the effect of cAMP-dependent and cAMP-independent positive inotropic agents in human myocardium.
Volatile anaesthetics have a variety of effects on the myocardium, namely a negative inotropic effect and a catecholamine sensitizing effect. The present study was designed to see if the hydrocarbon anaesthetics interact specifically with subcellular targets of the myocardial cell, by examining the effects of halothane in the presence of positive inotropic agents with different mechanisms of action. Experiments were performed in isolated electrically driven left ventricular preparations (1 Hz, 37 degrees C, Ca2+ 1.8 mmol litre-1) from human hearts obtained at cardiac surgery. The concentration-response curves of noradrenaline, milrinone, BayK 8644 and Ca2+ were investigated in the absence and in the presence of halothane. Halothane enhanced the efficacy of noradrenaline and milrinone but not of Ca2+ or BayK 8644. The potency of milrinone was also increased by halothane, whereas the potency of BayK 8644 was decreased and those of noradrenaline and Ca2+ were unchanged. Halothane differentially influences the effects of agents with different positive inotropic mechanisms. This experimental approach can be taken as a functional method to localize the mechanisms of action of the inhalation anaesthetics in human myocardium, namely sensitization of cAMP formation and interaction with L-type Ca2+ channels.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease.
There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gallstone formation and mitigate biliary pain in gallstone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gallbladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 x 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05 +/- 0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94 +/- 0.27 versus 0.93 +/- 0.32 mg/ml) or total protein (5.8 +/- 0.9 versus 6.4 +/- 1.3 mg/ml), cholesterol saturation (1.3 +/- 0.2 versus 1.5 +/- 0.2), or nucleation time (2.0 +/- 3.0 versus 1.5 +/- 2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9 +/- 0.6 versus 5.6 +/- 1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Drug death autopsies at the Munich Institute of Forensic Medicine (1981-1992).
A total of 638 drug death autopsy cases in southern Bavaria from 1981 to 1992 were analysed, including epidemiological and toxicological investigations. The rate of HIV infections decreased during the last few years. Cocaine does not (yet) play a major role. Suicide rates are high. Heroin intoxications are the most frequent cause of death, mostly in combination with other drugs and alcohol. In 1992 we observed a sharp increase of the number of deaths associated with dihydrocodeine abuse. This seems to be a local phenomenon and has to be explained by uncritical and uncontrolled prescription of large amounts of this opiate by individual physicians.
Academies and Institutes↗
[Isopropanol and acetone level in serum after preoperative surface disinfection with antiseptics containing isopropanol].
After preoperative skin disinfection in pediatric surgery, serum levels of isopropanol up to 12.2 mg/l (MW 5.0 mg/l +/- 3.37, n = 26) were found. They result from a rapid and prolonged but uncharacteristic percutaneous resorption of the isopropanol-containing disinfectant. In about 50% of the cases, serum levels of acetone showed an increase up to 82 mg/l already before skin disinfection, presumably caused by preoperative starvation. After skin disinfection, raised acetone levels were found in 19 of 26 cases. As increased isopropanol and acetone levels are discussed as alcoholism markers, a falsification of congener analysis after skin disinfection, e.g. in cases of adult victims of accidents, has to be taken into consideration. Endogenous serum levels of methanol (0.87 mg/l +/- 0.49), ethanol (0.32 mg/l +/- 0.09), acetaldehyde (0.31 mg/l +/- 0.10) and others remained unaffected. Some uncharacteristic elevations of propanol-1 levels are caused by contaminated rubber caps.
1-Propanol↗
[Statistical approach to forensic conversion values for alcoholics].
With collaboration of the study groups from Tübingen, Munich and Kiel and consideration of the results of Bonnichsen et al 1968, alcohol elimination curves of 98 alcoholics were subjected to a joint evaluation for determination of the beta 60 values. The average elimination rate was 0.21 g/kg/h (s = 0.05 g/kg/h). By analogy to average beta 60 values and back-conversion factors of nonalcoholics, the limit values for alcoholics were estimated as being between 0.12 g/kg/h (minimum value) and 0.29 g/kg/h (maximum value).
Adult↗
[Change in congener analysis caused by percutaneous absorption of propanol-containing antiseptics].
According to the forensic literature, an alteration of blood alcohol concentration through alcohol disinfection before venepuncture is unlikely, however, percutaneous resorption of alcohol containing antiseptics is well documented. There are no investigations available, elucidating to what extent this is also correct for congener alcohols, particularly propanol-1/-2, which have serum levels in range of mg/l. In experiments with surgical hand and local skin disinfection, carried out with and without oral alcohol, relevant levels of propanol-1/-2 between 0.2 and 2 mg/l were measured. We conclude, that the routine clinical use of antiseptics is able to alterate and to falsify congener levels and can lead to incorrect interpretation of congener analysis.
1-Propanol↗
Urinary excretion of acetylcyanamide in rat and human after oral and dermal application of hydrogen cyanamide (H2NCN).
The main urinary metabolite of hydrogen cyanamide (syn.: cyanamide) in rat and man is acetylcyanamide (syn.: N-acetylcyanamide). An analytical method was developed to determine acetylcyanamide in the urine with a limit of quantification of less than 10 micrograms/l (mean recovery 96.1% using spikes of 20 micrograms/l; relative standard deviation less than 4%). This methodology is based upon ion chromatography using column-switch techniques and UV detection. It could be demonstrated that in rats an average of 45.6% of oral applied cyanamide (10 mg/kg) was excreted in the urine as acetylcyanamide. In male human volunteers a mean of 40% of oral administered cyanamide (mean dose 0.25 mg/kg body weight) was excreted via the urine as acetylcyanamide. The same group of volunteers participated in a skin absorption study with dermal application of the above cyanamide dose onto a skin surface area of 32 cm2. Within an application period of 6 h an average cyanamide quantity of 2.3 mg was available for skin absorption. A mean portion of 7.7% of this quantity was found as acetylcyanamide in the urine of the participants. Findings from literature state that cyanamide is metabolized in vitro to cyanide. According to examinations performed in vivo, however, such a metabolic pathway seems to be irrelevant for man. In comparison with the control values there was no significant increase of both the cyanide concentrations in the blood and the thiocyanate concentrations in the urine of the above volunteers after the described oral cyanamide administration.
Administration, Oral↗
Reduced binocular depth inversion as an indicator of cannabis-induced censorship impairment.
Measurements of binocular depth inversion using a stereoscopic slide projection with polarized light were performed in healthy volunteers before and after cannabis intake. Since binocular depth inversion represents an illusion occurring in the perception of semantically meaningful objects projected in a 3-D inverted fashion, the hypothesis can be tested that cannabis-induced "psychedelic states" represent a condition in which the human CNS is unable to correct implausible perceptual hypotheses. The data demonstrate a strong cannabis-induced impairment of binocular depth inversion.
Adult↗
[Methanol metabolism in chronic alcoholism].
Serum methanol concentrations (SMC) exceeding 10 mg/l are highly suggestive of long-term alcohol intoxication and can be considered as marker for chronic alcohol abuse. Endogenously formed or consumed methanol is almost exclusively metabolized by alcohol dehydrogenase. As long as blood alcohol concentrations exceed 0.2-0.5 g/l methanol cannot be metabolized and accumulates. In a prospective study on 78 patients admitted for alcohol detoxification, elevated SMC up to 78 mg/l were found, with a mean SMC of 29.4 mg/l. No correlation was demonstrated between SMC and severity of the alcohol withdrawal syndrome. Further clinical, forensic and biochemical aspects of methanol metabolism are discussed.
Adult↗
Leber's hereditary optic atrophy: further evidence for a defect of cyanide metabolism?
We studied one patient with Leber's optic atrophy (LOA) in the acute stage and 12 at the chronic stage of the disease, and measured the activity of rhodanese in white blood cells and the level of cyanide in whole blood. In the patient with acute disease the blood cyanide level was significantly increased at first. Treatment of this patient with cyanide antagonists reduced his cyanide level, but this was not accompanied by improvement in visual function. Rhodanese activity was normal in all patients, as were the blood cyanide levels in each of the 12 patients at the chronic stage of the disease. These findings suggest a temporary disturbance of cyanide metabolism during the acute phase of the disease in this family. The abnormal metabolic mechanism was not identified.
Acute Disease↗
Reducing the amount of monomers in intraocular lenses through sterilization by gamma radiation.
Sterile inflammatory reactions of varying degrees are a rare, but not uncommon, complication after intraocular lens implantation. At present we still do not know the cause of these processes, but we consider two chemical substances contained in the lens at least as risk factors for them: monomeric methyl methacrylate, which is present in any lens made from polymethyl methacrylate (Perspex), and ethylene oxide, an extremely toxic agent, which is absorbed by the lens during sterilization with this gas. Gas chromatographic investigations show that under sterilization of intraocular lenses by 60Co radiation the amount of monomeric methyl methacrylate in the lens can be reduced drastically. Also, any contamination of the lens by ethylene oxide is avoided. Therefore, at least two important arguments speak in favor of this alternative sterilization technique.
Chromatography, Gas↗
[Comparison of benzodiazepine screening using the fluorescence polarization immunoassay (Abbott TDX) and thin layer chromatography in the area of low concentrations].
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Benzodiazepines↗