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Biomedical subjects

A S Christophersen

Publications and source records attributed to A S Christophersen.

At least 37 records · Page 2Linked to original sources

[Driving under the influence of alcohol, drugs and narcotics].

The National Institute of Forensic Toxicology has registered a large increase in the number of samples from drivers suspected of driving under the influence of drugs other than alcohol. Illegal and prescribed drugs are detected in an increasing number of cases. In many of these cases, the drugs are combined with alcohol. The most frequent drugs detected in 1992 in addition to alcohol were tetrahydrocannabinol (the psychoactive compound in cannabis) and benzodiazepines, mostly detected at blood concentrations above therapeutic levels. Simultaneous use of different benzodiazepines and use of benzodiazepines in combination with illegal drugs are common. The number of samples containing amphetamine showed a significant increase in 1992 compared with 1991 (an increase of 80%).

Alcohol Drinking↗

Automated sample preparation by on-line dialysis and trace enrichment. Analysis of morphine, 6-monoacetylmorphine, codeine, ethylmorphine and pholcodine in plasma and whole blood by capillary gas chromatography and capillary gas chromatography-mass spectrometry.

A fully automated sample preparation method for the determination of five opiates in human plasma and whole blood is described. The technique combines dialysis and trace enrichment prior to gas chromatography and gas chromatography-mass spectrometry. Dialysis and trace enrichment on a polymer column was shown to be a highly reliable method for sample preparation. The method can be used, after minor modification, to determine other basic drugs in plasma and whole blood. The method demonstrates the potential of the automated sequential trace enrichment of dialysate (ASTED) system for automated sample preparation.

Automation↗

Ethylmorphine metabolism in isolated rat hepatocytes.

The metabolism of ethylmorphine has been studied in suspensions of isolated rat hepatocytes. Early during incubation, the two major metabolic intermediates detected were morphine and norethylmorphine following N- and O-dealkylation of ethylmorphine, respectively. During subsequent incubation the concentration of the second metabolic intermediate, normorphine increased, before the concentration peaked at approximately 20 microM (100 microM ethylmorphine). Both morphine and normorphine were glucuronidated to form morphine-3-glucuronide and normorphine-3-glucuronide, respectively, which appeared to be the major metabolic end products. The percentage of ethylmorphine metabolized to morphine-3-glucuronide was found to be dependent on the initial concentration of ethylmorphine. With increasing initial ethylmorphine concentration the relative formation of morphine-3-glucuronide was reduced (29 +/- 10% at 5 microM, 18 +/- 5% at 20 microM, and 15 +/- 4% at 100 microM mean +/- S.D., n = 10). The concentrations of ethylmorphine and its metabolites were found to be higher in liver cells than in medium. Thus the ratios between the intra-/extra-cellular concentrations of ethylmorphine increased somewhat from an initial value of 4 during the period for which ethylmorphine could be detected intracellularly. The drug metabolites all exhibited ratios above 10 for the initial 100 min. of incubation. With time these ratios showed a decline, but even for prolonged incubation the ratios were 5 or higher for the end products. Thus considerable drug concentration gradients existed across the cell membrane of isolated rat hepatocytes.

Animals↗

Relationship between drug plasma concentrations and psychomotor performance after single doses of ethanol and benzodiazepines.

In a placebo controlled, crossover study psychomotor effects of single doses of diazepam, 10 and 20 mg, flunitrazepam, 1 and 2 mg, as well as 0.9 g ethanol/kg body weight were investigated over a time period of 6 h in 12 healthy men. Blood samples were collected simultaneously with the test sessions to determine drug concentrations in plasma or blood. The ethanol dose caused the least performance impairment, followed by 10 mg diazepam. The most pronounced impairment was caused by 2 mg flunitrazepam, whereas 20 mg diazepam and 1 mg flunitrazepam caused intermediate impairment and were approximately equipotent on group level. Considerable interindividual differences with respect to maximal impairment following a particular drug treatment were observed, with poor correlation between individual maximal impairments and individual peak plasma concentrations of the drug. The maximal impairment in simple reaction time following the flunitrazepam treatments occurred earlier relative to the peak plasma concentration of the drug as compared to the diazepam treatments. This may indicate that acute tolerance develops differently for the two drugs.

Adult↗

Simultaneous determination of common benzodiazepines in blood using capillary gas chromatography.

Blood samples were extracted with n-butyl acetate, and the extracts analysed by capillary gas chromatography using DB-1 and DB-1701 capillary columns with electron-capture detection. The DB-1701 column was found to give better separation of different benzodiazepines (BZDs). Recoveries ranged from 79 to 98%. Detection limits ranged from 0.005 to 0.015 microM for triazolam and flunitrazepam, and from 0.02 to 0.1 microM for other BZDs. Data on accuracy and precision are given for diazepam, desmethyldiazepam, flunitrazepam and nitrazepam.

Anti-Anxiety Agents↗

[Substance abuse analysis of biological materials].

Requests are increasing for biomedical analyses of abused drugs in forensic toxicology, tests at work, testing of drug addicts during rehabilitation, and in therapeutic and other situations. Special guidelines have been prepared in forensic toxicology, with regard to the legal background, information on any sanctions in the event of positive test results, chains of custody for handling samples, analytical methods with known specificity and sensitivity, and interpretation of results based on information of legal drug use. These guidelines should also be recommended in other cases if the results might lead to negative sanctions for the individuals involved. False positive test results have been recorded from cases analysed at local laboratories which had not established the recommended guidelines. The most critical point appears to be the confirmation of positive screening results using specific methods.

False Negative Reactions↗

Evaluation of a method for simultaneous quantification of codeine, ethylmorphine and morphine in blood.

Codeine, ethylmorphine and morphine are the most commonly detected opiates in forensic blood samples in Norway. A method for the simultaneous quantification of these opiates utilizing solid phase extraction and gas chromatography-mass spectrometry has been evaluated. The detection limits were 0.026 mumol/l for codeine, 0.025 mumol/l for ethylmorphine and 0.032 mumol/l for morphine (corresponding to 7.8, 7.8 and 9.1 micrograms/l, respectively). The analytical variations at concentrations of 1.0 mumol/l codeine, 1.0 mumol/l ethylmorphine and 0.5 mumol/l morphine were less than 5%.

Codeine↗

Metabolic study of pholcodine in urine using enzyme multiplied immunoassay technique (EMIT) and capillary gas chromatography.

A study of pholcodine metabolism in man is reported. Three subjects received a single therapeutic oral dose of 50 mg pholcodine and urine samples were collected as long as a positive opiate response could be detected by EMIT (16-26 days). Pholcodine was found to conjugate with glucuronic acid and 15% (13-17%) of the pholcodine dose was excreted in urine as the glucuronide, and 29% (24-35%) as unconjugated pholcodine. Morphine was detected to be a metabolite of pholcodine and 0.5-1% of the pholcodine dose was excreted as morphine glucuronide. The identity of morphine was confirmed by capillary gas chromatography-mass spectroscopy (GC-MS).

Adult↗

Determination of pholcodine and its metabolites in urine by capillary gas chromatography.

A sensitive and selective method for the determination of pholcodine and its metabolites in urine using capillary gas chromatography with nitrogen detection is described. The procedure includes enzymatic hydrolysis of urine by beta-glucuronidase and sample pretreatment on C2 solid-phase extraction columns. Validation of the method showed good sensitivity, precision and reproducibility. The method was useful for the study of pholcodine metabolism in man. Pholcodine was found to conjugate with glucuronic acid. Morphine was identified as a metabolite and another unidentified metabolite was also detected.

Chromatography, Gas↗

[The influence and use of drugs other than alcohol among drivers].

During the last few years, the National Institute of Forensic Toxicology has recorded an increasing number of cases of impaired driving due to drugs other than alcohol. Screening for drug use among drivers who are suspected of drunken driving only have also shown high frequencies of drug positive blood samples, indicating that a large number of drugged drivers are not discovered. Our results also show that the combined influence of both alcohol and drugs is common. Several new regulations were passed by the Norwegian Parliament in 1988 pursuant to the Norwegian Road Traffic Art. These new regulations include differentiation of sentences depending on blood alcohol concentration, introduction of evidential breath alcohol analysis and reduced use of clinical examination. The article discusses today's procedures for handling cases of suspected impairment by drugs. It is concluded that several problems will arise when dealing with cases of combined alcohol and drug impairment in accordance with the new Road Traffic Act, and that the introduction of evidential breath alcohol analysis and reduced use of clinical examination will make it more difficult to detect drugged drivers, particularly when they are also influenced by alcohol.

Alcohol Drinking↗

Screening for drug use among Norwegian drivers suspected of driving under influence of alcohol or drugs.

Two hundred and seventy blood samples selected at random from Norwegian drivers apprehended on the suspicion of drunken or drugged driving were screened for the presence of amphetamine, benzodiazepines, cannabinoids, tetrahydrocannabinol (THC) and cocaine. Of the samples tested, 223 were from drivers suspected of driving under the influence of alcohol only (A-cases). In the rest (n = 47) of the cases, the police also suspected drugs as a possible reason for driving impairment (D-cases). In the A-cases, benzodiazepines were found in 17%, cannabinoids in 26%, THC in 13% and amphetamine in 2% of the blood samples. One or more drugs besides ethanol were found in 38% of the A-samples. In the D-cases, benzodiazepines were found in 53%, cannabinoids in 43%, THC in 43%, amphetamine in 13% and 77% of these samples contained one or more drugs. Cocaine was not detected in any sample. Blood alcohol concentrations (BAC) above the legal limit of 0.05% were found in 80% of the drug positive A-cases and in 28% of the drug positive D-cases. The frequency of drug detection in A-samples was similar (40%) in samples with BAC above and below 0.05%, while this frequency was much higher (above 90%) in D-samples with BAC below 0.05% than in D-samples with BAC above 0.05% (53%). Benzodiazepines were most frequently found among drivers above 25 years of age, while cannabinoids were most frequently found among drivers below 35 years. For about 15-20% of the A-cases with BAC below 0.05%, other drugs were detected at concentrations which may cause driving impairment. It was concluded that analysis of alcohol only might often be insufficient in A-cases to reveal driving impairment.

Adolescent↗

Screening for drugs in forensic blood samples using EMIT urine assays.

A screening method for the detection of drugs in haemolysed whole blood has been evaluated. Methanolic extracts of 300 forensic blood samples known to be positive or negative for drugs were analysed with EMIT d.a.u. assay kits for amphetamine, cannabinoids, opiates and benzodiazepines (the latter to analyse for diazepam and the main metabolite N-desmethyldiazepam). There were very few false positive results, except for the amphetamine assay in postmortem blood samples, where 9% were false positive. For amphetamine and cannabinoids a few false negatives were found, these were from samples with very low drug concentrations. No false negatives were found for opiates and diazepam. The present modification of the EMIT d.a.u. method seems to be a good method for screening of drugs in forensic blood samples, except for amphetamine in postmortem samples. The method is simple and requires only 0.5 ml blood.

Amphetamine↗