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Biomedical subjects

G Kauert

Publications and source records attributed to G Kauert.

At least 19 recordsLinked to original sources

Determination of amphetamine and methylenedioxy-amphetamine-derivatives in hair.

Two GC/MS-procedures for the detection of amphetamine and its methylenedioxy-derivatives (MDA, MDMA and MDE) in hair are presented. In these methods a methanol sonication extraction technique was applied. The extracted drugs were derivatized either with propionic acid anhydride (PSA) or trifluoroacetic acid anhydride (TFA). PSA-derivatives are more stable than TFA-derivatives, but the latter provide more specific mass-spectrometric information, and, therefore, seem to be preferably for amphetamine determination. The detection limit for all compounds was in a range of about 0.01 ng/mg, if at least 50-100 mg of hair were analyzed, independent of the derivatization used.

3,4-Methylenedioxyamphetamine

Concentrations of delta 9-tetrahydrocannabinol, cocaine and 6-monoacetylmorphine in hair of drug abusers.

Hair samples taken from 850 individuals with presumed drug abuse were tested simultaneously for delta 9-tetrahydrocannabinol (THC), cocaine, heroin, the primary heroin metabolite 6-monoacetylmorphine (6-MAM) and morphine. The drugs were extracted with methanol under sonication. Compared to other extraction procedures this solvent extraction technique provides high extraction yields and less experimental effort. The analyses were carried out using gas chromatography-mass spectrometry (GCMS) in selected ion monitoring (SIM) mode. This procedure allows the simultaneous detection of amphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA) and methylenedioxylamphetamine (MDE). THC was found in 104 (12.2%), cocaine in 230 (27%) and 6-MAM in 141 (16.6%) samples. In addition to 6-MAM, morphine was detected in 87 (10.2%) and heroin in 38 samples (4.5%). The concentrations found were in a range 0.009-16.7 ng/mg for THC, 0.037-129.68 ng/mg for cocaine, 0.028-79.82 ng/mg for 6-MAM, 0.045-53.14 ng/mg for heroin and 0.011-7.800 ng/mg for morphine. The statistical distribution of the drug concentrations compared with the self-reported consumption behaviour of the users may possibly lead to a better understanding of the relationship between drug dosage and corresponding concentrations in hair.

3,4-Methylenedioxyamphetamine

Quantification of dimethindene in plasma by gas chromatography-mass fragmentography using ammonia chemical ionization.

A gas chromatographic-mass fragmentographic method using ammonia chemical ionization for the determination of dimethindene in human plasma is described. The drug was isolated from plasma by liquid-liquid extraction with hexane-2-methylbutanol. Plasma components were separated on a capillary column coated with chemically bonded methyl silicone. For detection of dimethindene, its quasi-molecular ion (M + H+) was mass fragmentographically monitored after chemical ionization with ammonia as reagent gas. Dimethindene was quantified using methaqualone as the internal standard: the quantification limit in plasma was 0.2 ng/ml, the within-run precision was 8.0% and the inter-run precision 5.6%. The plasma concentration-time profile was established after a single dose of 4 mg of dimethindene with an average maximum concentration of 5.5 ng/ml, detectable up to 48 h post application.

Ammonia

[Legal medicine aspects of current abuse potential].

Abuse is defined as use of a thing, which deviates from the original use and its purpose resp. in qualitative as well as quantitative manner. The task of the forensic medicine is to evidence the abuse and the misused substance resp. in order to find a basis for the judgement of the ability of the offenders guilt. The potential of abuse of several psychotropic drugs and their proof with its possibilities and limitations are described.

Drug and Narcotic Control

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

Benzodiazepine dependence: detoxification under standardized conditions.

In an analysis of the withdrawal syndrome of 12 patients dependent on benzodiazepines (BZD), important factors such as underlying psychiatric disease, precipitating life events, complaints leading to BZD use, and also positive and negative psychological and social consequences, duration of intake, dose and type of BZD dependence are discussed. Withdrawal was completed under standardized inpatient conditions reducing the BZD dose to 50% of the previous dose once every 5 days and maintaining control through regular measurements of the BZD urine concentrations. The course of the somatic, psychological and perceptual withdrawal phenomena was documented according to Lader's BZD withdrawal symptom checklist (Lader, M. (1983) J. Clin. Psychiatry 44, 121-127). The reduction scheme proved to be safe and efficient; no major withdrawal syndromes developed. Abstinence phenomena largely disappeared within 10 days of discontinuation.

Adult

[Plasma and urine catecholamines in a 7-day survival of parathion poisoning].

During the intensive medical treatment of a finally fatal parathion poisoning (survival time 7 days) with shock symptoms (lung and kidney) the kinetic profiles of both plasma and urinary catecholamines were taken up. In addition the parathion concentrations of the same plasma samples were measured. There could have been found plasma catecholamine profiles exhibiting peak concentrations in the initial phase, followed by a period of 4 days without any detectable plasma epinephrine and finally an extreme elevation of both catecholamines in the last period before death. The excretion patterns confirmed the plasma results. Imaginable pathophysiological mechanisms in consideration of the shock induced renal insufficiency are discussed. The question is raised whether the kinetics of plasma catecholamines may be a possible marker for the prognosis of organophosphate poisoning.

Aged

[The kinetics of plasma catecholamine in alkylphosphate poisoning and their therapy].

In connection with the "endogenous acetylcholine-poisoning" due to organophosphorous compounds beside the clinical important muscarinic and nicotinic symptoms an activation of the sympathetic nervous system (adrenal medulla, sympathetic ganglia) is expected. Therefore a kinetic profile of norepinephrine and epinephrine in the plasma of two patients with severe parathion-poisonings was taken up through the whole period of the intensive-medical treatment. The method used was HPLC with electrochemical detection. The parathion-concentration of the same plasma samples were measured, too. The result were individual different courses with periodically appearing, markedly increased plasma catecholamine values. A direct correlation of catecholamines with the parathion-concentration was not recognizable. A possible influence of the atropine-treatment as well as of stress-factors is discussed but estimated as not responsible for the observed peaks.

Adult

Longitudinal study on pharmacodynamics and pharmacokinetics of acute, steady-state and withdrawn quazepam.

To assess pharmacodynamic and pharmacokinetic properties of acute, subchronic and withdrawn quazepam, a single-blind, longitudinal study was run in eight male, healthy young volunteers. The design covered a 1-week placebo run-in period, a period with daily oral night-time administration of 15 mg quazepam until a pharmacokinetic steady-state was reached (3 weeks) and a 2-week placebo withdrawal period. Oculodynamic Test (ODT) (EOG-registration with simultaneous choice reaction task, CRT) and Adaptive Pursuit Tracking Test (APTT) were used for assessment of intradiurnal and long-term profiles of attention, perception, cognition, objective sedation, psychomotor and muscular (force-related) parameters and cardiorespiratory measures under workload. Visual analogue scales (VAS) of sedation, excitation and state anxiety were applied additionally. Plasma levels of quazepam and its metabolites (oxoquazepam and desalkyl-oxoquazepam) were intermittently analyzed by GC, within 24 h after actual blood sampling in the morning of assessment days, to check the attainment of the intended criterion for termination of medication (steady-state, "on-line kinetic procedure"). Adverse effects were recorded by subjects' written free recall and a symptom-checklist. Although a pharmacokinetic steady-state could be reached in sequence for the parent drug quazepam and its metabolites within 3 weeks, there was no pharmacodynamic steady-state at the end of this period, but a continuous impairment in oculomotor variables. Performance in the choice reaction task and the APTT showed a similar tendency, which was masked to a certain extend by learning effects. There were no signs for rebound effects within the 2 weeks after withdrawal. Relevant carry-over phenomena declined after 3 days of withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Detection of oxilofrine in plasma and urine by high-performance liquid chromatography with electrochemical detection and comparison with gas chromatography-mass spectrometry.

A high-performance liquid chromatographic (HPLC) method with electrochemical detection for the determination of oxilofrine [1-(4-hydroxyphenyl)-2-methylaminopropanol] in human plasma and urine (before and after cleavage of the metabolic conjugates) is described. Isolation from biological fluids is performed batchwise by weak acid cation exchange. Separation of plasma and urine components is achieved on a reversed-phase C18 column as an ion pair with heptanesulphonic acid. For amperometric detection the potential of the electrode was set at 0.95 V versus an Ag/AgCl reference electrode. The detection limit for oxilofrine in plasma is 1 ng/ml and in urine 12.5 ng/ml at a signal-to-noise ratio of 2.0 using 1.0 ml of plasma and 0.02 ml of urine. The method was compared with a gas chromatographic-mass spectrometric method and showed a good concordance for plasma (r = 0.996) and urine (r = 0.994). With the HPLC method it is also possible to determine related sympathomimetic drugs, e.g., etilefrine, norefenefrine or octopamine, after a slight modification of the mobile phase.

Chromatography, High Pressure Liquid

Clinical pharmacokinetics after a single oral dose of oxilofrine.

In a combined pharmacokinetic and clinical trial the correlation was investigated between plasma levels of oxilofrine and the haemodynamic effects on eight healthy volunteers after an oral dose of 120 mg oxilofrine. Plasma levels of free oxilofrine were measured by capillary gas chromatography mass fragmentography. Cardiovascular as well as echocardiographic parameters (left ventrical extent and velocity of fractional shortening) have been measured. The results pharmacokinetically showed a marked enterohepatic reabsorption profile with a second oxilofrine plasma peak occurring in between the second and third hours. The heart rate and mean arterial blood pressure remained unchanged. The total peripheral resistance was deceased on average. Systolic blood pressure increased by a maximum of 13.8%, the diastolic decreased by 8.8%. Increasing of the extent of left ventrical fractional shortening by 20.9% and the velocity by 29.5% indicated a positive inotropic effect, which was long lasting and not accompanied by chronotropic effects. There is a direct positive correlation between oxilofrine plasma levels and the extent of fractional shortening of left ventrical diameter (r = 0.981).

Administration, Oral

Dose linearity and relative bioavailability testing of oxilofrine, a sympathicomimetic drug, in healthy volunteers.

Single oral doses of 16, 32 and 64 mg oxilofrine as dragées as well as 16mg as drops were given to 12 healthy male volunteers in an open Latin-square design with one week interval between dosing days. Concentrations of unchanged drug were monitored in plasma over 24 hours, in urine concentrations of free and total oxilofrine were monitored over 36 hours. Drug concentrations were measured by a specific high pressure liquid chromatography method with electrochemical detection. Medians of maximum plasma concentrations (Cmax) of oxilofrine were 9.1 ng/ml, 11.4 ng/ml, 31.4 ng/ml and 122.9 ng/ml for 16 mg drops, 16, 32, and 64 mg dragées, respectively. The times to maximum plasma concentration (tmax) were between 0.7 and 1.7 h, respectively. The values for areas under the plasma concentration-time curve (AUC0-24) were 12.8, 17.7, 61.0 and 268.2 ng/ml.h for the four treatments. The results show that both Cmax- and AUC0-24-values increase faster with increasing dosing than a linear first-pass would suggest and give evidence for a saturable first-pass metabolism. There is also evidence for an enterohepatic circulation. About 50% of the administered dose is found in the urine, urinary recovery shows a dose-linear dependency. General tolerability was good; no side-effects were reported.

Adult

Concentrations of mustard gas [bis(2-chloroethyl)sulfide] in the tissues of a victim of a vesicant exposure.

An Iranian soldier died at a toxicological intensive care unit at Munich seven days after a vesicant exposure. At the autopsy the typical symptoms of mustard gas intoxication were found. The vesicant was detected qualitatively by gas chromatography-mass spectrometry (GC-MS) in the abdominal fat and quantified in the tissues and in the body fluids by the following method: (1) extraction by dichloromethane, (2) cleanup of the extracts by thin-layer chromatography (TLC) on silica plates, (3) extractive derivatization with gold-chloride, and (4) quantitative determination by electrothermal atomic absorption spectrometry (ET-AAS). The equal extracts, after heating, served for blanks. The following concentrations were found (milligrams of mustard gas/kilograms of tissue wet weight): brain 10.7, cerebrospinal fluid 1.9, liver 2.4, kidney 5.6; spleen 1.5, lung 0.8, muscle 3.9, fat 15.1, skin 8.4, skin with subcutaneous fatty tissue 11.8, liquid from a skin blister: below detection limit, blood 1.1, and urine: below detection limit.

Adult

Cadmium body burden of an occupationally non burdened population in southern Bavaria (FRG).

The cadmium body burden of the occupationally non-burdened population in the southern Bavarian area was estimated from the cadmium concentrations in liver and renal cortex, determined by ET-AAS of 263 autopsy cases. A mean value of 17.9 mg cadmium was calculated for all cases and 21.9 mg cadmium for all adults. The body burdens found do not depend on sex but greatly on smoking habits. Mean values for non-smokers are 13.5 mg, for moderate smokers 22.5 mg and for heavy smokers 33.2 mg. The dependence on age is similar to that of the cadmium concentration in the kidney cortex: an increase up to an age of approximately 50 years and a decrease at higher ages. Between the average value we found and the critical body burden calculated by Roels et al. (1983) is a safety factor of 8 to 10, but in some of our cases of middle-aged, heavy smokers this safety factor drops to a value lower than 1. It is concluded that it seems to be imperative to control the further trend of the cadmium body burden in occupationally non-burdened populations.

Adolescent