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Biomedical subjects

O H Drummer

Publications and source records attributed to O H Drummer.

At least 37 records · Page 2Linked to original sources
PubMed1996

Gas chromatographic-mass spectrometric determination of beta 2-agonists in postmortem blood: application in forensic medicine.

A solid-phase extraction procedure is described for the simultaneous determination of terbutaline, salbutamol and fenoterol in human postmortem whole blood, using gas chromatography-electron impact mass spectrometry. The limit of quantitation in 1 ml of blood was 1 ng/ml for all analytes. A linear response was observed over the concentration ranges tested, covering both low and high concentrations of each drug. The recoveries in postmortem blood were: terbutaline, 88%; salbutamol, 86%; fenoterol, 92%; orciprenaline (internal standard), 86%. Coefficients of variations for both intra-assay precision and inter-assay reproducibility ranged between 2.2 and 13.0% for all analytes. This method is sensitive and selective, and has been applied successfully to over 60 postmortem blood specimens.

Adrenergic beta-Agonists↗
PubMed1996

Solid phase extraction of morphine and its metabolites from postmortem blood.

A simple and rapid high-performance liquid chromatographic method is described for the determination of morphine-3-glucuronide, morphine-6-glucuronide, normorphine and morphine in postmortem blood. A solid phase extraction technique employing C18 Sep-Pak cartridges was used to recover morphine and its metabolites from 0.5 ml of blood. Reverse phase ion-pair chromatography was used to achieve separation with a C18 bonded column. The mobile phase consisted of acetonitrile, lauryl sulphate and sodium dihydrogen orthophosphate buffer at low pH. Electrochemical detection (ECD) in series with ultraviolet (UV) spectrophotometric detection (210 nm) was used for quantitation. The lower limit of detection using ECD was 10 ng/ml for all analytes and a linear response was observed to 5000 ng/ml. Coefficients of variation for all analytes ranged between 3-13% for both intra- and inter-assay. This method is reproducible, quick and easy to perform and allows morphine conjugates and morphine to be measured simultaneously in postmortem blood.

Adult↗
PubMed1996

Involvement of codeine in drug-related deaths.

The incidence and role of codeine in drug-related deaths in Victoria was investigated over a 5-year period. There were a total of 107 cases involving codeine, representing 8.8% of all drug-related deaths in this period in Victoria. There were only six fatalities in which codeine was considered the major poison. The mean (+/- SD) concentration of codeine in femoral blood was 4.0 +/- 2.3 mg/L (range, 2.1-8.0 mg/L). The mean concentration of free codeine was 1.3 +/- 0.9 mg/L (range, 0.4-2.8 mg/L). The remaining 101 cases involved a combination of codeine and other drugs. The mean total codeine blood concentration was 1.8 +/- 3.3 mg/L (range, 0.04-26 mg/L), which was significantly lower than in those cases where codeine was the major poison (p < 0.002). The mean concentration of free codeine was 0.82 +/- 4.9 mg/L (range, 0.02-9.0 mg/L), which was not significantly different (p > 0.05) from the six codeine-only cases. The most common drugs found in this group, other than codeine, were acetaminophen (62%), diazepam (46%), salicylate (20%), and ethanol (25%). The association of other psychoactive drugs in these deaths made the contribution of codeine difficult to assess. Free codeine concentrations > 0.4 mg/L and total codeine concentrations > 2.0 mg/L may be sufficient to cause death in the absence of any other contributing factors.

Acetaminophen↗
PubMed1996

Sudden death and benzodiazepines.

A study of 16 deaths associated with toxic concentrations of benzodiazepines during the period of 5 years leading up to July 1994 is presented. Cases where other drugs, including ethanol, had contributed to the death were excluded. All cases were subject to a full macroscopic and microscopic examination by pathologists, and all cases were subject to a full toxicological work-up. Preexisting natural disease was a feature of 11 cases. In the remaining five cases, death was caused solely by benzodiazepines. There were 14 suicides. Nitrazepam and temazepam were the most prevalent drugs detected, followed by oxazepam and flunitrazepam. Minimum toxic femoral blood concentrations of 7-aminonitrazepam, 7-aminoflunitrazepam, and oxazepam were estimated as 0.5, 0.2, and 2 mg/L, respectively. Relating these deaths to prescription rates in Victoria suggest that flunitrazepam may be inherently more toxic if misused than other benzodiazepines currently available on the Australian market.

Adult↗
PubMed1995

High-performance liquid chromatographic procedure for the measurement of nitrobenzodiazepines and their 7-amino metabolites in blood.

A simple and sensitive HPLC method is described for the determination of the nitrobenzodiazepines, nitrazepam, flunitrazepam and clonazepam and their respective 7-amino metabolites in post-mortem blood. Using a single-step extraction the nitrobenzodiazepines were recovered from 0.5 ml of blood using butyl chloride. The solvent was evaporated to dryness and the reconstituted residue injected onto an HPLC system. Separation was achieved using a phenyl-bonded reversed-phase column with an acetonitrile-phosphate buffer mobile phase. Ultraviolet detection (240 nm) was used for quantitation. A linear response was observed between 0.01 and 0.60 mg/l. Assay precision between and within assays was less than 20% for all analytes. The limits of detection ranged from 0.001 to 0.008 mg/l with a limit of quantitation of 0.01 mg/l for all analytes.

Chromatography, High Pressure Liquid↗
PubMed1995

Death due to benzhexol toxicity.

A rare case of death due to benzhexol toxicity is reported in a 48-year-old schizophrenic male with a resolving empyema and underlying patchy, mild bronchopneumonia. Toxicological analysis revealed the benzhexol blood and liver concentrations to be 0.12 mg/l and 0.5 mg/kg, respectively. Gastric contents contained 0.4 mg of benzhexol. Other drugs were not detected. It is suggested that for fatalities to occur following benzhexol intoxication, secondary contributory factors, which probably further alter the patient's conscious state, are necessary.

Bronchopneumonia↗
PubMed1995

Postmortem drug metabolism by bacteria.

Studies were undertaken to determine the possible role of enteric bacteria in the postmortem bioconversion of the nitrobenzodiazepines flunitrazepam, clonazepam, and nitrazepam. Flunitrazepam, clonazepam, and nitrazepam were completely metabolized in blood in the presence of eight species of enteric bacteria to their respective 7-amino-metabolites. The rates of metabolism, at 37 degrees C, ranged from 0.1 ng/mL/min for Streptococcus faecalis to 8.8 ng/mL/min for Clostridium perfringens. The rate of conversion was reduced to 87% by a combination of 0.7% (w/v) sodium fluoride and potassium oxalate, and almost completely inhibited (96%) by 1% (w/v) sodium fluoride. pH had variable effects on the rate of metabolic bioconversion of nitrobenzodiazepines, while increasing temperatures were found to generally increase the rate of nitrobenzodiazepine bioconversion. These data support the proposal that bacteria may mediate postmortem bioconversion of the nitrobenzodiazepines.

Adult↗
PubMed1995

Extraction of psychotropic drugs from human scalp hair.

A comparison of techniques for the extraction of antidepressant and antipsychotic drugs in human scalp hair is described. Human scalp hair was obtained from cadavers known to be taking psychotropic drugs prior to their death. Following a washing step, hair was either solubilized in sodium hydroxide, or treated with dilute hydrochloric acid, methanol or subtilisin. Digests were treated with a solvent and the extracted drugs quantified by high performance liquid chromatography. The alkaline digestion procedure was found to be significantly more effective (P < 0.01) in recovering a range of antidepressant and antipsychotic drugs from hair than either the acidic, methanolic or enzymatic treatments.

Chromatography, High Pressure Liquid↗
PubMed1995

Detection of antidepressant and antipsychotic drugs in postmortem human scalp hair.

The presence of therapeutic drugs in postmortem human scalp hair was investigated. Hair samples from 21 cadavers known to have taken antidepressant and antipsychotic drugs were solubilized in 1 M sodium hydroxide. Drugs were extracted using solvent extraction procedures and analyzed by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). Antidepressant drugs detected were amitriptyline, dothiepin, doxepin, imipramine, trimipramine, and mianserin. Antipsychotic drugs detected were haloperidol, chlorpromazine and thioridazine. Concentrations of these drugs and their metabolites ranged from 1.3 to 242 ng/mg hair. Segmental analysis demonstrated that the drug concentrations detected were either consistent with the known dosing regime of the deceased, or were able to provide an indication of drug use within the last few months prior to death. This study reinforces the potential of hair as a useful tissue in forensic investigations, in establishing a history of past exposures to therapeutic drugs.

Antidepressive Agents↗
PubMed1994

A single-dose comparison of the bioavailability of aluminium from two formulations of sucralphate in normal volunteers.

The oral bioavailability of aluminium was compared after administration of 1 g sucralphate as either a tablet or a suspension (1 g/5 ml) in a crossover study in 16 healthy volunteers. Aluminium levels were detectable in all subjects pre-dose (21.4 +/- 8.8 micrograms l-1 before tablet; 21.4 +/- 7.4 micrograms l-1 before suspension) and there was a measurable increase in the plasma concentrations of aluminium in all subjects after administration of the suspension, and in 14 of the subjects after administration of the tablet formulation, with Cmax reached within the first 8 h in most subjects. Plasma levels were still elevated 72 h after dosing. The variability in plasma levels of aluminium was significantly higher after administration of the suspension (CV 39-53%) than after administration of the tablet (CV 29-44%), reflecting greater absorption of aluminium from the suspension formulation in three subjects. Similarly, the variance of the Cmax, AUC(0-72 h), and AUC(0-infinity) (for both the raw data and the baseline adjusted data) were all higher for the suspension than for the tablet. A point estimate of the difference of the pharmacokinetic parameters (determined from the median of the arithmetic Walsh averages) indicated little or no difference in Cmax, Tmax, or AUC(0-infinity) in the two formulations. In summary, the performance of the suspension formulation of sucralphate is more variable than the tablet formulation in vivo and some patients may therefore have higher circulating levels of aluminium on therapy with the suspension formulation.

Administration, Oral↗
PubMed1994

Responsibility analysis: a methodology to study the effects of drugs in driving.

In order to study the role of drugs in driving, a responsibility analysis was developed to allow an assessment to be made of the driver's culpability or responsibility in an accident. Factors possibly mitigating drivers' responsibility in each accident were identified and scored. Factors considered were: condition of road, condition of vehicle, driving conditions, accident type, witness observations, road law obedience, difficulty of task, and level of fatigue. If a sufficient number of mitigating factors were identified a driver would be found to be either partly or totally exonerated from blameworthiness and scored either as a contributory or nonculpable driver. If drugs present in a driver contributed to accident causation, it would be expected that they would be overrepresented in culpable drivers, i.e. those drivers not exonerated from blame. A total of 341 driver fatalities occurring in Victoria were analysed for blood alcohol content (BAC). Twenty-nine percent had a BAC over .05% (the legal limit in Victoria). Alcohol-positive drivers were statistically overrepresented in the culpable group (p < .001), in single-vehicle accidents (p < .05) and those accidents in which vehicles left the road for no apparent reason (p < .001). Odds-ratio estimation of relative risk of culpable and nonculpable drivers showed that the relative risk rose disproportionately to BAC.

Accidents, Traffic↗
PubMed1994

Delayed death following carbon monoxide poisoning. A case report.

The body of a deceased woman was found in a car. The circumstances were typical for suicidal carbon monoxide (CO) poisoning by inhalation of exhaust gases, except that the vacuum cleaner hose had become detached from the exhaust. Autopsy revealed only decompositional changes. No CO or other drugs were detected. Hypoxic changes were present in the cortex and hippocampus, with an age of 2-3 days. It is consistent that this woman inhaled sufficient CO to cause coma, at which stage the hose became detached, and that she then exhaled CO over the next 2-3 days before finally dying. Delayed death following CO poisoning is an uncommon occurrence. This case is reported because of its unusual nature.

Adult↗
PubMed1994

A fatality due to flurazepam.

A fatality attributed to suicidal ingestion of up to 2.2 grams of flurazepam is described. The deceased was a 52-year old female with a history of depression and suicidal attempts. No significant pathology was found at autopsy. Full toxicological analyses detected only flurazepam and metabolites in her tissues. The concentrations of flurazepam in femoral blood, liver, bile, vitreous humor and urine were 5.5 mg/L, 130 mg/kg, 33 mg/L, 1.3 mg/L and 3.3 mg/L, respectively. Analysis of gastric contents showed 600 mg of flurazepam. Desalkylflurazepam was also detected in blood, liver, bile and vitreous, but at much lower concentrations than the parent compound.

Chromatography, Gas↗
PubMed1994

A study of deaths involving oxycodone.

Nine deaths involving oxycodone were investigated to assess the contribution of this opiate to these fatalities. All except one of the bodies were subjected to a full autopsy by specialist pathologists with a subsequent thorough toxicological examination. No significant anatomical pathology was found at autopsy. All deaths gave concentrations of oxycodone in femoral blood higher than expected following normal therapeutic use. In three cases no other drug in toxic concentrations was detected. Two cases involved the presence of a high concentration of a benzodiazepine and in a further two cases a high concentration of alcohol in addition to other drugs in therapeutic concentrations were present. One case involved methamphetamine in significant concentrations and another involved high concentrations of oxazepam in combination with pethidine. In all cases the presence of oxycodone was given as a factor contributing to the death. In only one case were there circumstances clearly indicating suicide. Our observations suggest that oxycodone is at least as toxic as other opiates and will cause deaths if misused.

Adult↗
PubMed1994

Death following colchicine poisoning.

A 45-year-old male was admitted to hospital after 2 to 3 days of vomiting, nausea, and diarrhea following an apparent overdose of colchicine tables. During hospitalization his white blood cell count fell dramatically. At death, 33 h following initial hospitalization, pleural effusion with bilateral bronchopneumonia was evident, together with numerous bacterial colonies and marked hypocellularity of bone marrow and reduced megakaryocytes, erythroid, and myeloid cells. The most striking histological findings were numerous metaphasic mitotic figures in gastric and small bowel epithelia. Colchicine was detected, confirmed by high pressure liquid chromatography with photodiode array detection, and quantitated in antemortem plasma collected 3.3 h following hospitalization and in postmortem blood and bile. Colchicine was not detected in liver, vitreous humor, or stomach contents.

Bile↗