Biomedical subjects

Olaf H Drummer

Publications and source records attributed to Olaf H Drummer.

24 records · Page 2Linked to original sources

PubMed2002

Methadone dose and post-mortem blood concentration.

The relationship of methadone dose with post-mortem blood concentration was investigated using data collected from 1994 coronial cases in the Australian state of New South Wales. Data on 31 subjects were summarized using linear regression. The weight-adjusted methadone dose, gender, methadone maintenance treatment status and its interaction with adjusted-dose were all significant predictors of post-mortem blood methadone concentration. Data on the death of a young man from the toxic effects of three daily doses of 30 mg methadone are used to give an example of a pair of observed (0.74 mg/l) and predicted (0.48 mg/l) post-mortem blood concentrations. The estimated post-mortem blood concentration for male maintenance patients is at least twice the trough plasma levels estimated from previously published studies of living maintenance patients. The estimated post-mortem blood concentration for female maintenance patients is at least three times the estimated trough level of living subjects. We conclude that post-mortem methadone redistribution is probably the principal cause of the observed differences between males and females in post-mortem blood concentrations and the differences between estimated concentrations for living and deceased subjects.

Drug Overdose↗

PubMed2002

Postmortem drug analysis: analytical and toxicological aspects.

Publications focusing on the analysis of postmortem specimens for the presence of drugs were reviewed with particular reference to systematic toxicological analysis. Specimens included blood, liver, other solid specimens, and fly larvae. Extraction techniques published during the past 10 years most commonly used traditional solvent extraction techniques. High-performance liquid chromatography coupled to multichannel wavelength detection was most commonly used, which would easily lend itself to liquid chromatography-mass spectrometry. There were few practical differences in the assays validated for a range of postmortem specimens to those in other forms of forensic toxicology, unless substantially decomposed tissue was used. When putrefied specimens were analyzed, a back-extraction or other form of specimen cleanup was recommended to reduce interfering substances. Many immunoassays designed for urine have been adapted for use in blood and tissue homogenates. Immunoassays designed for blood analysis, however, are likely to have more useful cutoff values than immunoassays optimized for urine testing. Postmortem specimens provide less stability for a number of drugs than other types of specimens. This is particularly a problem for cocaine, heroin, and some antidepressants, antipsychotics, and benzodiazepines. A number of artifacts occur postmortem, which affects the concentration of drug in specimens. This includes postmortem redistribution for drugs with a high tissue concentration relative to blood. Consequently, the likely extent of any change in concentration is relevant to the interpretation of doses and drug effects.

Animals↗

PubMed2002

Fatal methadone toxicity: signs and circumstances, and the role of benzodiazepines.

OBJECTIVE: To describe the signs and symptoms and circumstances of fatal methadone toxicity and investigate the role of benzodiazepines in these deaths. METHODS: Data were extracted from 1994 New South Wales (NSW) coronial files and cause of death established independently. Cases were grouped according to the likely source of methadone. Data describing the clinical history and circumstances of death were extracted from witnesses' and police statements. RESULTS: Methadone contributed to the deaths of 57 of the 87 adult coronial cases in which it was detected in NSW in 1994. The most commonly reported early signs of severe methadone toxicity were ataxia, slurred speech and evident euphoria. The late signs were unconsciousness, loud snoring and brown pulmonary oedema fluid coming from the mouth or nose. Death occurred an average 5.1 and 6.0 hours after oral ingestion and intravenous injection of methadone, respectively. Benzodiazepines were significantly more likely to have contributed to deaths from methadone toxicity among maintenance patients and people taking methadone tablets for pain relief than deaths involving diverted methadone syrup and deaths to which methadone did not contribute (OR 4.8, 95% 1.7 to 14.4). CONCLUSIONS AND IMPLICATIONS: Benzodiazepines may contribute to deaths from methadone toxicity by increasing upper airways obstruction. Victims would have had a greater chance of survival if they had either been placed in the coma position or given mouth-to-mouth ventilation and an ambulance had been called. Benzodiazepines are more likely to contribute to fatal methadone toxicity in newly admitted maintenance patients and those taking methadone tablets for pain relief.

Adult↗

PubMed2002

Postmortem concentrations of citalopram.

The postmortem concentrations of citalopram in blood, bile, liver, and vitreous humour were investigated in 14 cases using a specially developed high performance liquid chromatography assay. Concentrations from drug and non-drug related deaths were categorized to determine a postmortem therapeutic and toxic range. Therapeutic citalopram concentrations for blood, bile, liver, and vitreous humour ranged to 0.4 mg/L, 2.1 mg/l, 6.6 mg/kg, and 0.2 mg/L, respectively. In one potentially fatal response to citalopram, concentrations were 0.8 mg/L, 6.0 mg/L, 0.3 mg/L for blood, bile and vitreous humour, respectively.

Adult↗

PubMedDate not supplied

Determination of delta9-THC in whole blood using gas chromatography-mass spectrometry.

A simple and reliable liquid-liquid extraction method for the determination of delta9-tetrahydrocannabinol (THC) in whole blood utilizing gas chromatography-mass spectrometry in electron impact mode is described. The substance is derivatized with pentafluoropropionic anhydride in pentafluropropanol. The limit of detection is 0.5 ng/mL for a 1-mL specimen, with recovery greater than 70%. The intra-assay coefficient of variation (CV) is 3.1% to 5.2%, and the interassay CV is 6.4% to 9.5%, calculated at THC concentrations of 1, 5, and 25 ng/mL. The accuracy is between 95 and 97%. The optimization of extraction and derivatization conditions is detailed.

Buffers↗

PubMedDate not supplied

LC-MS analysis of serotonergic drugs.

Separating drugs which are both polar and basic has long been difficult because of the limited operating pH range of conventional HPLC columns. This paper describes a liquid chromatographic method capable of being used with either diode-array or mass spectrometric detection for the identification and quantitation of 10 antidepressant and 2 antipsychotic drugs, all of which have serotonergic activity. In developing the method, the effects of varying buffers and mobile phase pH and of adding modifying agents on resolution and capacity factors were investigated. The organic buffers ammonia, glycine, and triethylamine were each used in a mobile phase made up of 32.5% buffer/67.5% methanol (v/v) at a pH of 10.0. Additionally, four different concentrations each of tetrahydrofuran and acetonitrile were added to investigate the effect of a modifying agent on resolution and retention. In general, decreasing mobile phase pH reduced retention times and decreased resolution. Adding tetrahydrofuran in place of the same amount of methanol tended to decrease retention times, and adding acetonitrile tended to slightly increase retention times. However, addition of both marginally improved resolution. This method has been used to satisfactorily analyze brain, blood, liver, urine, vitreous fluid, and stomach contents in subjects known to have used these drugs.

Antidepressive Agents↗