Postmortem redistribution of morphine and its metabolites

The postmortem redistribution of morphine, morphine-3-glucuronide, morphine-6-glucuronide and total morphine was assessed in 40 heroin-related deaths. In blood taken from subclavian, heart, and femoral regions, concentrations of morphine and its metabolites were similar. While there was a trend for higher concentrations in heart blood, when compared with femoral or subclavian blood, this was not significant. There was also no significant difference in concentrations between admission and autopsy blood in which the postmortem interval was on average 59 h. From our observations, significant postmortem redistribution of morphine and its metabolites seems unlikely.     

Review: Pharmacokinetics of illicit drugs in oral fluid

This article reviews studies that have measured drug concentrations in oral fluid following controlled dosing regimens. A total of 23 studies have been identified over the last 15 years. These show that the amphetamines including designer amphetamines, cocaine, cannabis and cocaine are quickly found in oral fluid following dosing and usually have similar time-courses to that in plasma. Following common doses peak oral fluid concentrations exceed 0.1 microg/mL and often even 1 microg/mL. The drug concentration will depend on whether a dilution step occurs with buffer as part of the sampling procedure. The uses of collectors that stimulate oral fluid usually reduce the drug concentration compared to a non-stimulated manner. This reduction will not disadvantage the recipient since it will potentially reduce the detectability of drug in oral fluid compared to non-stimulated collections. Only one recent study has been reported for a benzodiazepine. This showed nanogram per milliliter concentrations for flunitrazepam. More studies are required for benzodiazepines and indeed for other drugs, particularly in multiple drug situations and where disease may affect the pharmacokinetics of drugs.     

Demands on scientific studies in different fields of forensic medicine and forensic sciences. Traffic medicine--impaired driver: alcohol, drugs, diseases

Since human performance is a key factor in crash causation detailed knowledge of the involvement of alcohol, drugs and diseases is of fundamental interest for road safety. To better understand the effect of these influencing factors it is important to use a combination of witness observations and a range of experimental and epidemiological studies. Epidemiological approaches to research such as road-side-surveys, case-control-studies, culpability analysis, pharmaco-epidemiological studies are usually seen as being able to provide the best answers. This article discusses the relative merits of experimental and epidemiological approaches.     

Age estimation and the developing third molar tooth: an analysis of an Australian population using computed tomography

The third molar tooth is one of the few anatomical sites available for age estimation of unknown age individuals in the late adolescent years. Computed tomography (CT) images were assessed in an Australian population aged from 15 to 25 years for development trends, particularly concerning age estimation at the child/adult transition point of 18 years. The CT images were also compared to conventional radiographs to assess the developmental scoring agreement between the two and it was found that agreement of Demirjian scores between the two imaging modalities was excellent. The relatively wide age ranges (mean ± 2SD) indicate that the third molar is not a precise tool for age estimation (age ranges of 3-8 years) but is, however, a useful tool for discriminating the adult/child transition age of 18 years. In the current study 100% of females and 96% of males with completed roots were over 18 years of age.     

Carbon monoxide concentrations in the 2009 Victorian Bushfire disaster victims

Blood was available for the estimation of carboxyhemoglobin saturation (COHb) in 30 of the 173 persons who died in the Victorian bushfires in February 2009. The ages of these 30 deaths ranged from 3 to 80 years and there were 8 females. 13 cases (43%) were considered negative (less than 5% COHb), 12 (40%) were between 5 and 40% COHb, 2 (6.7%) between 40 and 50% and 3 (10%) were greater than 50% COHb. There were 6 persons either found within a building or a car and the COHb in these cases ranged up to 69% (mean 50%). There were 5 cases where the location was unable to be determined as either indoor or outdoor due to the extensive nature of the fire. The remaining 19 deceased persons were all located outside in the open and the concentration of COHb in these cases ranged up to 30% (mean 19%). Hydrogen cyanide was only detected in two deceased persons at concentrations of 0.5 and 2.7 mg/L, respectively. 13 deceased were found to have soot in the airways following necropsy but this did not correlate with the COHb levels.     

The incidence of drugs of impairment in oral fluid from random roadside testing

Oral fluid (OF) has become a popular specimen to test for presence of drugs, particularly in regards to road safety. In Victoria, OF specimens from drivers have been used to test for the presence of methylamphetamine (MA) and Δ(9)-tetrahydrocannabinol (THC) since 2003 and 3,4-methylenedioxy-N-methylamphetamine (MDMA) since 2006. LC-MS/MS has been used to test the most recent 853 submitted OF specimens from Victoria Police for 31 drugs of abuse including those listed in the Australian Standard AS4760-2006. At least one proscribed drug was detected in 96% of drivers, of which MA was the most common (77%), followed by THC (42%), MDMA (17%) and the combination of all three (3.9%). Opioids were detected in 14% of drivers of which 4.8% were positive for 6-acetylmorphine and 3.3% for methadone. The incidence of the opioids tramadol (1.2%) and oxycodone (1.1%) were relatively low. Cocaine (8.0%) was as commonly detected as benzodiazepines (8.0%), and was almost always found in combination with MA (7.9%). Samples positive to benzodiazepines were largely due to diazepam (3.5%) and alprazolam (3.4%), with only 0.2% of drivers combining the two. Ketamine was also detected in 1.5% of cases. While the incidences of the proscribed drugs itself are concerning, it is clear that many drivers are also using other drugs capable of causing impairment.     

The prevalence of drugs in injured drivers

In mid 2009 Victoria introduced compulsory drug testing of blood taken from all injured drivers taken to hospital. Δ(9)-Tetrahydrocannabinol (THC), methylamphetamine (MA) and 3,4-methylenedioxy-methylamphetamine (MDMA) are prohibited and if drivers are positive to any amount an automatic penalty is enforced. Laboratory screens were conducted on preserved blood using ELISA testing for cannabis metabolite and methylamphetamines and a fully validated LC-MS/MS method for 105 drugs including THC, amphetamines, opioids, benzodiazepines, antidepressants and antipsychotics and a number of other psychoactive substances using a minimum of two transitions per drug. Conventional GC-testing for ethanol was used to screen and quantify the presence of alcohol. 1714 drivers were tested and showed alcohol in 29% (≥ 0.01 g/100mL) and drugs in 35%. The positive rate for the three drugs prohibited by legislation was 12.5%. The prevalence of THC, MA and MDMA was 9.8%, 3.1%, and 0.8%, respectively. The range of THC concentrations in blood was 2-42 ng/mL (median 7) of which 70% had a concentration of 10 ng/mL or higher. The range of concentrations for MA and MDMA was 0.02-0.4 and 0.03-0.3mg/L (median for both drugs was 0.05 mg/L). Drugs of any type were detected in 35% of cases. The other drugs were largely prescribed drugs such as the antidepressants (9.3%) and benzodiazepines (8.9%). Neither 6-acetylmorphine nor cocaine (or benzoylecgonine) was detected in these cases.     

Brain distribution of selected antipsychotics in schizophrenia

The brain distribution of phenothiazine antipsychotics in 22 confirmed schizophrenic and 11 control subjects were collected at autopsy. Specimens were homogenized, extracted with n-butyl chloride, and analyzed via liquid chromatography-mass spectrometry, using atmospheric pressure electrospray ionization operating in the positive mode. Drug concentrations normalized for those observed in cerebellum showed three distinct patterns of distribution corresponding to different structural features of each type of phenothiazine. Those drugs with high affinity for dopamine receptors were detected in the highest concentrations in regions with high concentrations of such receptors. However, those associated with relatively lower dopaminergic activity were found in the highest concentration in the occipital cortex, a region with a relatively low concentration of dopamine receptors. The regional brain distribution of thioridazine and its metabolites was concentration dependent. These results have implications for determining the role of these drugs in the sudden and unexpected deaths of schizophrenics.