A retrospective review of methylamphetamine detected in child deaths reported to the Victorian Coroner, Australia.

This study investigated methylamphetamine (MA) exposures in the deaths of children (≤ 12 years old) reported to the Coroner in the state of Victoria, Australia, between 2011 and 2020. Demographics, autopsy findings including the cause of death, self-reported prenatal or caregiver drug use, child protection services information, and toxicological findings were summarized by descriptive statistics. Validated methods of liquid chromatography-tandem mass spectrometry were used in the analysis of drugs. There were 50 child deaths with MA detected in blood, urine, and/or hair with 64% (n = 32) identified in 2018-2020. Most children were 1-365 days old (66%, n = 33) and the cause of death was unascertained in 62% (n = 31) of cases. MA was toxicologically confirmed in hair (94%, n = 47) significantly more than blood (18%, n = 9). Prenatal or caregiver drug use was self-reported in 44% (n = 22) and 42% (n = 21) of cases, respectively. Moreover, only 54% (n = 27) of deceased children were a child protection client at their time of death. These findings suggest the number of deceased children exposed to MA has increased over the past 10 years, which is consistent with the greater supply of crystal MA in the Australian community. Hair analysis provided additional means to identify cases that were unknown to child protection services and may have implications for other children in the same drug exposure environment.

Quantitative analysis of tetrahydrocannabinol isomers and other toxicologically relevant drugs in blood.

A multi-analyte liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described, involving the separation of delta-9-tetrahydrocannabinol (delta-9-THC) and delta-8-THC in addition to other commonly encountered drugs and metabolites. Briefly, sample preparation involved an alkaline liquid-liquid extraction (methyl tert-butyl ether) of blood (100 µl). The solvent layer was transferred, evaporated to dryness, reconstituted, and samples then separated on an Agilent Poroshell 120 EC-C18 100 Å (50 mm × 3.0 mm, 2.7 µm) analytical column using a multi-step gradient elution of 50 mM ammonium formate in water (pH 3.5) and 0.1% formic acid in methanol over 14 min. A SCIEX Triple Quad 6500+ system operating in scheduled multiple reaction monitoring and positive electrospray ionization was used for detection. There were no interferences, and matrix effects were generally acceptable (±20% of neat response). Linearity was achieved within the calibration range, including methylamphetamine (MA) (10-1000 ng/ml), 3,4-methylenedioxy-N-methylamphetamine (MDMA) (10-1,000 ng/ml), cocaine (10-1000 ng/ml), and two THC isomers (1-100 ng/ml). Accuracies of MA, MDMA, cocaine, and two THC isomers were 3.6 to 8.9%, -1.2 to 4%, -5.3 to 5.8%, and -11 to 14%, respectively; while precision estimates of the same were 1.6 to 5.4%, 1.7 to 5.3%, 1.2 to 4.5%, and 2 to 10%, respectively. Autosampler stability and dilution integrity were within acceptable limits, and no carryover was detected at the limit of detection. This validated LC-MS/MS method made the routine identification of both delta-9-THC and delta-8-THC in blood possible.

Methylamphetamine toxicity and its involvement in death: A retrospective observational study of deaths reported to the Victorian Coroner, Australia.

A retrospective observational study of Victorian deaths involving MA between 2010 and 2019 was conducted to determine the prevalence and contribution of methylamphetamine (MA) toxicity to death in the absence of other factors. Demographics, autopsy findings, toxicology, and the cause of death were reviewed. Coronial cases were categorized into five groups: deaths due to MA toxicity in the absence of other factors (Group A1); deaths due to MA toxicity in the setting of other potentially contributing factors (Group A2); deaths due to MA toxicity in the setting of significant natural disease (Group B); deaths primarily due to multiple-drug toxicity (Group C); and deaths primarily due to natural causes (Group D). There were 506 deaths involving MA categorized into Group A1 (n = 1, 0.6%), Group A2 (n = 8, 1.6%), Group B (n = 28, 5.5%), Group C (n = 229, 45%), and Group D (n = 240, 47%). Significant natural disease was prevalent among deaths involving MA and mainly concerned forms of cardiovascular disease (n = 277, 55%). The MA concentration in the one death included in Group A1 was 2.1 mg/L. The median MA concentrations of Group A2 (1.6 mg/L) and Group B (0.5 mg/L) were significantly higher than Group C (0.2 mg/L) and Group D (0.2 mg/L). Additionally, many other toxicologically significant drugs were detected and mostly comprised of central nervous system depressants. Deaths due to MA toxicity in the absence of other factors were rare despite the greater availability of crystal MA in the Australian community. The study highlights the interpretative challenges of MA blood concentrations and the continuing harms of this drug in Australia.

Changing trends and characteristics of one punch deaths in Australia (2012-2018).

One-punch assaults also known as 'coward punches', are characterised by a single severe blow to the head causing the victim to lose consciousness, resulting in a secondary impact between the head and surrounding environment. Such impacts may result in brain injury leading to fatality or permanent neurological impairment. In a previous publication, there were 90 one punch deaths around Australia between 2000 and 2012, mostly involving young men drinking alcohol at a licensed venue at the weekend. This prompted a surge of public education and awareness campaigns around Australia, in addition to regulatory and legislative changes aimed at curbing social violence. This retrospective descriptive study aimed to examine one punch deaths since 2012 in Australia to determine if there has been a decrease in deaths, and whether the demographics and circumstances of these deaths have changed. A search of the National Coronial Information System was undertaken for all closed coronial cases between 1 January 2012 and 31 December 2018. Additional information was collected from medicolegal reports including toxicology, pathology and coronial findings. There were 80 one punch fatalities in Australia, almost exclusively involving males. The median age was 43.5 (range 18-71) years and there was a decreasing trend in the number of deaths annually. Most fatal assaults occurred in the state of New South Wales (28.8%) followed by Queensland (23.8%), and in metropolitan locations (64.6%) rather than regional areas (35.4%). Alcohol was the most commonly detected drug, found in 47 cases of the 71 cases where toxicology results were available (66%), with a median concentration of 0.14 and 0.19 g/100 mL in antemortem and postmortem samples, respectively (range 0.005-0.32 g/100 mL). Five deaths reported methylamphetamine, with THC detected in 21.1% of cases. Assaults more commonly occurred on a footpath or roadside (41.3%), followed by a home or dwelling (32.5%). 8.8% of assaults occurred inside hotels, bars or other licenced venues. Most transpired on a weekday, which differed from the pre-2012 period when these assaults occurred mainly on the weekend. While some trends are positive, there has been a shift in the victim demographic as well as the typical environment for fatal one punch assaults, highlighting the importance of public health surveillance in providing a current evidence base to inform policy and practice.

False-Positive Amphetamines in Urine Drug Screens: A 6-Year Review.

Immunoassays are routinely used to provide rapid urine drug screening results in the clinical setting. These screening tests are prone to false-positive results and ideally require confirmation by mass spectrometry. In this study, we have examined a large number of urine specimens where drugs other than amphetamines may have caused a false-positive amphetamine immunoassay screening result. Urine drug screens (12,250) in a clinical laboratory that used the CEDIA amphetamine/ecstasy method were reviewed for false-positive results over a 6-year period (2015-2020). An additional 3,486 referred samples, for which confirmatory--mass spectrometry was requested, were also reviewed. About 86 in-house samples and 175 referral samples that were CEDIA false-positive screens were further analyzed by an LC-QTOF general unknown screen. Potential cross-reacting drugs were identified, and their molecular similarities to the CEDIA targets were determined. Commercial standards were also analyzed for cross-reactivity in the amphetamine/ecstasy CEDIA screen. Positive amphetamine results in 3.9% of in-house samples and 9.9% of referred tests for confirmatory analysis were false positive for amphetamines. Of these false-positive specimens, on average, 6.8 drugs were detected by the LC-QTOF screen. Several drugs were identified as possible cross-reacting drugs to the CEDIA amphetamine/ecstasy assay. Maximum common substructure scores for 70 potential cross-reacting compounds were calculated. This was not helpful in identifying cross-reacting drugs. False-positive amphetamine screens make up to 3.9-9.9% of positive amphetamine screens in the clinical laboratory. Knowledge of cross-reacting drugs may be helpful when mass spectrometry testing is unavailable.

Fatal Intoxications from a Combination of 4-Fluoroamphetamine and 25C-NBOMe.

Six fatalities have occurred from the ingestion of a combination of new psychoactive substances (NPSs), 4-fluoroamphetamine (4FA) and 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25C-NBOMe) over a 9-month period. Four of these fatalities (one older female and three young males) were from direct adverse effects of drugs, and one each from a fall while being intoxicated and during restraint. All cases were subject to full postmortem examinations that included collection of femoral blood. The four drug-caused fatalities had postmortem blood concentrations for 4FA and 25C-NBOMe of 330-682 ng/L (median 417) and 1.4-12 ng/mL (median 4.3), respectively. The other two cases (both young males) where death was considered to have been caused indirectly by drug intoxication had 4FA and 25C-NBOMe postmortem concentrations of 21 and 123 ng/mL, and 1.8 and 4.5 ng/mL, respectively. None of these cases showed concentrations of drugs that suggested use of high recreational doses. In one drug-caused death, capsules and a brown powder obtained from the scene were found to contain a mixture of these two NPSs. With the exception of one drug-caused death, other drugs were detected; however, the effects of the two NPSs together were regarded as the primary triggers for the deaths. There were no consistent symptoms or pathology in these cases; however, agitation/aggression was observed in two cases prior to their collapse, with seizures in possibly three cases. Pulmonary and/or cerebral edema was noted in three cases. Potentially significant natural disease (a mildly enlarged heart) was only observed in one drug-caused case. These cases illustrate a possible increased risk of sudden death with this combination of drugs, both of which can elevate serotonin concentrations as well as act as strong stimulants. These cases also illustrate the difficulty in detecting NPS in cases where no prior information is available that might suggest their use.

Stimulant use in suicides: A systematic review.

Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides attributable to substance use. This systematic review investigated any potential associations of stimulant use detected in post-mortem biological specimens and suicides. We conducted a systematic review and narrative synthesis (CRD42021237966). Medline, EMBASE, TOXLINE, and Scopus databases were searched for terms related to forensic toxicology, post-mortem toxicology, suicide and stimulants. The primary outcome was to estimate the prevalence of stimulant use in suicides. There were 26 studies whichcontributed to prevalence measures; in studies reporting at the individual compound level, suicides involved cocaine (0.1-23%), caffeine (3.2-22%), 3,4-methylenedioxymethamphetamine (0.1-17%), amphetamine (0.2-9.3%), methamphetamine (3.1-7%), and phentermine (0.9-1%). Overall, stimulant use in suicides was over-represented compared to estimates of stimulant use in the general population and has increased over time. Thirteen case reports used to contextualise suicides involving stimulants found no examples of cocaine or methamphetamine mono-intoxication of suicidal intent. This suggests mechanisms other than acute toxicity involved in stimulant-associated suicide. Future research by in-depth psychological autopsies of suicides involving stimulants, in combination with segmental hair analysis to determine the chronicity of stimulant exposure, may contribute to a better understanding of the burden of suicide attributable to stimulant use.

Fire/flames mortality in Australian children 1968-2016, trends and prevention.

INTRODUCTION: Mortality attributed to fire and flame for children (0-14 years) over a fifty-year period has not been previously analyzed in Australia. The literature has focused on these deaths over a shorter time period or disaggregated with other causes of burns or deaths in one burns center. However, mortality associated with fire/flames affects this age group the greatest. The aims of this study are to: (1) develop a trends analysis of fire and flames mortality between1968 to 2016, using the Australian Bureau of Statistics (ABS) mortality database and, (2) determine the association of interventions with fire and flames mortality using the Haddon's categorical intervention framework. METHODS: International Classification of Disease (ICD) codes were extracted and code equivalencies between ICD 8, 9, 10 and the Australian Bureau of Statistics for fire/flames data between 1968--2016 were assessed. To determine whether population changes affected the risks of mortality, the frequency and, rates per 100,000 were used. A literature review was conducted that summarized the current knowledge of interventions associated with the major decreases in the fire and flames mortality rate. RESULTS: In Australia, we found was a downward trend for the period although with significant variation from year to year when compared to external cause mortality. Additionally, there were multiple successful interventions associated with a sustained decrease in mortality. After 2016, child fire-related mortality remains a problem particularly in low socioeconomic groups and indigenous peoples. A combination of research, public awareness, engineering, legal enforcement, advancements in burns care and, evidence-based policy development all have a role to play in future injury prevention initiatives. Although direct causation to an individual is not possible, associations can be drawn from interventions on a population level to decreases in mortality. CONCLUSION: We found was a steady decline in both rates and frequency of childhood fire and flames mortality from 1968 to 2016 associated with multiple interventions.

Urine toxicology screening by liquid chromatography time-of-flight mass spectrometry in a quaternary hospital setting.

OBJECTIVE: Validation of a non-targeted method for urine drug screening (UDS) by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF), and comparison to an established GC-MS method in a hospital setting. METHODS: 217 UDS specimens sent to a quaternary hospital pathology department, were analysed by a CEDIA® immunoassay screen (six drug panels; amphetamines, barbiturates, benzodiazepines, cocaine metabolites, cannabinoids and opiates) on an Abbott Architect instrument. Specimens were subsequently analysed by an established non-targeted qualitative GC-MS method and results compared with a general unknown screening method by LC-QTOF that was under evaluation as a replacement method. RESULTS: 42 selected drugs were evaluated; limits of identification ranged from 2 to 100 µg/L and most drugs (n = 39) were stabile for 24 h after preparation. Matrix effects greater than 25% were observed in seven of the selected drugs. 87% of the specimens tested positive to 1 or more drug panels in a CEDIA® screen. A total of 537 positive drug findings were identified by GC-MS compared to 1,267 positive findings by LC-QTOF. On average, each GC-MS screen identified 2.5 ± 1.8 drugs and the LC-QTOF screen identified 5.8 ± 3.2 drugs. No drugs were identified in 11.3% of the GC-MS screens, whereas drugs were detected in 99% of these by the LC-QTOF. In almost all instances, the LC-QTOF screen could provide mass spectrometric confirmatory results of positive immunoassay screens and was able to identify a wider range of additional drugs and drug metabolites. CONCLUSIONS: The described general unknown screening (non-targeted, qualitative) LC-QTOF method can detect a larger range of drugs encountered in a hospital setting. The method has been shown to be suitable for comprehensive toxicology screening in a clinical toxicology laboratory.

The prevalence of alcohol and other drugs in fatal road crashes in Victoria, Australia.

BACKGROUND: Driving under the influence of drugs, including alcohol, is a globally recognised risk factor for road traffic crashes. While the prevalence of alcohol and other drugs in fatal road crashes has been examined in other countries, recent data investigating drug driving in fatal Australian crashes are limited. This study aimed to examine how the presence of alcohol and other drugs in fatal road trauma in Victoria has changed over time in different road users. METHODS: A population-based review of road trauma deaths was performed over the period of 01 July 2006 to 30 June 2016 in Victoria, Australia, using data from the National Coronial Information System (NCIS) and the Victorian State Trauma Registry (VSTR). Drugs were grouped according to type and analysed accordingly. Poisson regression models were used to determine change in incidence rates over the study period. RESULTS: There were 2287 road traffic fatalities with complete toxicology data (97% of all road traffic fatalities). Alcohol (blood alcohol concentration, BAC) was the most commonly detected drug (>0.001 g/100 mL: 21.1%; >0.05 g/100 mL: 18.4%), followed by opioids (17.3%), THC (13.1%), antidepressants (9.7%), benzodiazepines (8.8%), amphetamine-type stimulants (7.1%), ketamine (3.4%), antipsychotics (0.9%) and cocaine (0.2%). Trends demonstrated changing use over time with specific drugs. Alcohol positive road fatalities declined 9% per year in passenger car/4WD drivers (IRR = 0.91, 95% CI: 0.88-0.95). The incidence of strong opioids (oxycodone, fentanyl, morphine, and methadone) increased 6% per year (IRR = 1.06; 95% CI: 1.02-1.10). Methylamphetamine was detected in 6.6% of cases and showed a yearly increase of 7% (IRR = 1.07; 95% CI: 1.01-1.13). The incidence of THC remained unchanged over the period, observed in 13.1% of cases. Stronger opioids were more commonly detected among pedal cyclists (19.0%) and pedestrians (20.9%) while THC was more commonly detected among motorcyclists (19.8%) and other light vehicle drivers (17.6%). CONCLUSIONS: A decline in the prevalence of alcohol in fatalities suggests that law enforcement and public health strategies in Australia to address road fatalities and drink-driving may have had a positive effect. However, increases were observed in the incidence of other potentially impairing drugs including opioids and amphetamines, specifically methylamphetamine, indicating a concerning trend in road safety in Victoria that warrants further monitoring.

Pharmacokinetic study of midazolam and α-hydroxymidazolam in guinea pig blood and hair roots after a single dose of midazolam.

The appearance of midazolam (M) and its metabolites into the hair root following a single administration was examined by following the time course of M and α-hydroxymidazolam (αHM) in hair roots and blood from guinea pigs. The back hair of guinea pigs was shaved before drug administration and before each sampling, and hair roots (3-5 mm) were plucked at 5, 15, and 30 min, 1, 2, 4, 6, 10, 24, 48, 72, 96, 120, 144 h, and 7, 14, 21, and 28 days. The kinetic parameters of M and αHM in guinea pig blood and hair roots were determined for three doses (5, 10, and 25 mg/kg). Comparisons of drug time course between hair roots and blood indicated an association between drug concentrations in the hair root and the blood. M and αHM entered the hair root within 5 min after a single exposure. The detection windows were also longer for the hair root than for the blood. Consequently, the hair root can be a valuable specimen in acute poisonings or drug-facilitated crime (DFC) cases, if other matrices are unavailable, or if blood and urine results are negative. Hair shafts (with hair roots) were plucked at 28 days and segmented. The concentrations of M and αHM were lower in the hair shafts than in the hair roots. The concentrations of the metabolite αHM in hair shafts were barely detectable. The concentrations of M and αHM in the hair root showed a moderate correlation with dose. Comparison of drug levels in hair roots between the washed group and the unwashed group indicated a generally stable percentage between the washed and unwashed groups of 40-60 % during the entire time course. This indicates that drugs are likely to be immobilized in the hair root at the beginning of the incorporation process.

Postmortem Drug Redistribution: A Compilation of Postmortem/Antemortem Drug Concentration Ratios.

Postmortem drug redistribution (PMR) is a well-known phenomenon in forensic toxicology with implications for medico-legal death investigations. Paired antemortem (AM) specimen and postmortem (PM) mortuary admission femoral blood drug concentrations from 811 coronial cases were used to construct a retrospective compilation of PM/AM drug concentration ratios for 42 parent drugs and metabolites. The median PM/AM ratios for all antidepressants were > 1 and consistent with PMR In contrast, the median PM/AM ratios of most benzodiazepines were < 1. The antipsychotics were varied (0.63-3.3) and suggest the mixed effects of PMR and drug instability. Amphetamines exhibited no trends (0.90-0.95) and are likely confounded by many factors. The PM/AM ratios of cardiovascular drugs, opioids and other drugs are also reported. This research represents an expansive retrospective compilation of paired AM and PM drug concentrations for many toxicologically relevant drugs. While the median PM/AM ratios demonstrate some drug-dependent trends, there was no obvious relationship between AM specimens and PM femoral blood taken at mortuary admission.

High Throughput Detection of 327 Drugs in Blood by LC-MS-MS with Automated Data Processing.

The described procedure provides a rapid technique for the detection and semi-quantitation of a large number of drugs in blood. This procedure uses a minimal sample volume and employs a one-step liquid extraction and automated data processing to yield rapid turnaround times. A total of 327 of the most commonly used medicinal and illicit drugs in Australia were selected including various amphetamines, anesthetics, antidepressants, antipsychotics, anticonvulsants, benzodiazepines, beta blockers, opioid and nonopioid analgesics, stimulants, THC and a large number of synthetic cannabinoids and other novel psychoactive substances. The extracts were subject to 5-minute chromatography using a Kinetex C18 50 × 4.6 mm 2.6 µm solid-core analytical column and analyzed using a Sciex 3200 Q-TRAP MS-MS (+ ESI, MRM mode, two transitions per analyte). The method was fully validated in accordance with international guidelines. Matrix effects and extraction efficiencies were acceptable with most analytes showing > 80% response and low variation (within 25%RSD). Cannabinoids were most affected by the matrix and yielded poorest recovery values but were still detectable. Precision, accuracy, repeatability and multipoint linearity were assessed for all analytes. The method has been used in routine practice in the forensic toxicology service at the Victorian Institute of Forensic Medicine in over 6000 coronial investigations using both postmortem and clinical blood specimens. This technique has greatly increased throughput, reduced turnaround times and allowed for rapid same-day analysis of results when needed. The method is routinely used in routine overnight testing with results reported to pathologists within 4 h of data acquisition. This rapid toxicological technique is used in conjunction with other investigative processes such as full-body CT imaging, review of case circumstances and medical histories to provide an efficient death investigation process.

Time-Dependent Changes in THC Concentrations in Deceased Persons.

Changes in the concentrations of Δ9-tetrahydrocannabinol (THC) in the postmortem period were investigated in a series of cases by comparing concentrations in blood taken on receipt of the body in the mortuary (admission specimen, AD) with the concentrations obtained in blood taken at autopsy some time later and also from blood specimens taken antemortem. Overall, the median THC concentration in AD blood was 13.7 ng/mL (n = 239, range LOQ-220), while the median concentration at autopsy was 13.8 ng/mL (n = 106, range LOQ-810) and 1.9 ng/mL (n = 147, range LOQ-48) antemortem. Fourteen cases had all three specimens taken from the same decedent. The corresponding AM, AD and PM median concentrations were 4.0 (range LOQ-48), 15.5 (range 4.0-176) and 4.4 ng/mL (LOQ-56), respectively. The median elapsed times from AM to AD and AD to PM were 33 and 97.5 h, respectively. In contrast, acetaminophen showed no change in blood concentration from AM to AD (6.8 and 6.0 mg/L, respectively). These data show large increases in THC concentration in the early postmortem period, followed by a decline, although the median blood concentrations at autopsy were similar to that obtained antemortem. In contrast, when blood was taken from the femoral region, subclavian and heart ventricles sites, in the same case, the THC concentrations, while variable, showed overall no significant difference. These dynamic changes reflect complex phenomenon occurring in deceased persons and will further serve to increase the uncertainty over any interpretation of postmortem THC concentrations.

Detection of a New Tert-Leucinate Synthetic Cannabinoid 5F-MDMB-PICA and Its Metabolites in Human Hair: Application to Authentic Cases.

Methyl 2 -[ [ 1- (5- fluoropentyl) indole - 3- carbonyl] amino] -3, 3- dimethyl - butanoate (5F-MDMB-PICA) is a new synthetic cannabinoid characterized by valinate or tert-leucinate moieties. In recent years, 5F-MDMB-PICA has been abused in the form of "spice-like" herbal incenses or electronic cigarette oil. A UHPLC-MS/MS method was developed to detect 5F-MDMB-PICA and its metabolites in human hair. Approximately 20 mg of hair was weighed and pulverized with methanol below 4°C. After ultrasonication, centrifugation and filtration, 200 µL of supernatant was placed into an autosampler vial and analyzed on a Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm particle size) using an acetonitrile-20 mmol/L ammonium acetate (0.1% formic acid, 5% acetonitrile) gradient with a run time of 8 min. The limit of detection (LOD) ranged from 0.5 to 5 pg/mg, and the lower limit of quantitation (LLOQ) ranged from 1 to 5 pg/mg. The method was shown to be linear over a concentration range of 1-200 pg/mg. The linear correlation (R 2) of the calibration curves for all analytes was >0.999. The accuracy varied from 95.4 to 107.4%, while the intra- and inter-day precision RSD values were 0.7-10.6% and 1.7-12.2%, respectively. Recoveries were within the range of 61.1-93.3%, and matrix effects were in the range of 19.1-102.6%. The validated method was successfully applied to the identification and quantification of 5F-MDMB-PICA and its metabolites in hair from authentic forensic cases.

UHPLC-MS/MS method for simultaneously detecting 16 tryptamines and their metabolites in human hair and applications to real forensics cases.

Tryptamines are hallucinogenic substances many of which have appeared recently as novel psychoactive substances (NPS). Herein, we describe the establishment of a rapid UHPLC-MS/MS quantitative method for the targeted screening of 16 tryptamines of abuse in hair. Twenty milligram pieces of hair were pulverized below 4 °C in 0.5 mL of deionized water containing 0.1% formic acid and an internal standard (2 ng/mL psilocin-d10 and psilocybin-d4). After subsequent centrifugation, 5 µL of the supernatant was injected into a LC-MS/MS system fitted with a Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm). The column was gradient eluted at 0.3 mL/min with mobile phases composed of 20 mmol/L ammonium acetate, 5% acetonitrile, and 0.1% formic acid in water (solvent A) and acetonitrile (solvent B). Limits of detection ranged between 0.1 and 20 pg/mg, with limits of quantitation ranging from 3 to 50 pg/mg. The calibration curves for all analytes were linear (r > 0.992). Accuracies varied between 91% and 114%, with intraday precision RSDs < 14% and interday precision RSDs of between 1.3% and 14%. The recoveries of all tryptamines were in the 85-115% range, with the matrix effect ranging from 95% to 112%. The validated method was successfully used to analyse 191 hair samples from suspected tryptamine users, 77 of which were 5-MeO-DiPT-positive, while the 16 tryptamines and their metabolites were not detected in the remaining 114 hair samples. 5-MeO-DiPT and its 5-MeO-NiPT, 5-OH-DiPT, and 4-OH-DiPT metabolites were concurrently detected in 34 hair samples. 5-MeO-DiPT, as the parent drug, was the parent substance found in the hair samples.

Odds of culpability associated with use of impairing drugs in injured drivers in Victoria, Australia.

Culpability analysis was conducted on 5000 drivers injured as a result of a vehicular collision and in whom comprehensive toxicology testing in blood was conducted. The sample included 1000 drivers for each of 5 years from approximately 5000-6000 drivers injured and taken to hospital in the State of Victoria. Logistic regression was used to investigate differences in the odds of culpability associated with alcohol and drug use and other selected crash attributes using the drug-free driver as the reference group. Adjusted odds ratios were obtained from multivariable logistic regression models in which other potentially explanatory driver and crash attributes were included. Drivers with alcohol present showed large increases in the odds of culpability similar to that seen in other studies investigating associations between blood alcohol concentration and crash risk. Methylamphetamine also showed a large increase in the odds of culpability (OR 19) compared to the reference group at both below and above 0.1 mg/L, whereas those drivers with Δ9-tetrahydrocannabinol (THC) present showed only modest increase in odds when all concentrations were assessed (OR 1.9, 95 %CI 1.2-3.1). Benzodiazepines in drivers also gave an increase in odds (3.2, 95 %CI 1.6-6.1), but not other medicinal drugs such as antidepressants, antipsychotics and opioids. Drivers that had combinations of impairing drugs generally gave a large increase in odds, particularly combinations of alcohol with THC or benzodiazepines, and those drivers using both THC and methamphetamine.

Fatalities caused by novel opioids: a review.

Drugs related to morphine represent not only large range of important therapeutic applications for the relief of moderate to severe pain but also give rise to a relatively large series of novel opioids that mimic the action of this naturally occurring analgesic. Most of these are based on fentanyl structures that are much more potent, and dangerous, than fentanyl itself. This publication reviews reports of fatalities attributed to 15 novel opioids with the view to assessing mortality associated with their misuse as well as reviewing published analytical procedures that would be able to detect these and other novel opioids. These drugs include reports of deaths to acetylfentanyl, acrylfentanyl, butr(yl)fentanyl, carfentanil, 2- and 4-fluorofentanyls, 4-fluorobutyrfentanyl, 4-fluoroisobutyrfentanyl, furanylfentanyl, α- and 3-methylfentanyls, 4-methoxyfentanyl, ocfentanil, as well as AH-7921, U-47700 and MT-45. Most of these cases reporting a drug-caused death involved other drugs in addition to the opioid. No obvious minimum fatal concentration was discerned for any of the opioids for which details were provided, however, the more potent members required detection limits well under 1 ng/mL and often even well below 0.1 ng/mL requiring use of the most sensitive mass spectral detection procedures, particularly when screening specimens using a non-targeted mode. Four other novel opioids have been reported in admissions to hospitals include 4-chloroisobutryfentanyl, cyclopentylfentanyl and tetrahydrofuranfentanyl, all of which are likely to have the potential to cause death. It is also likely that other analogues will appear with time.

Cannabis as a cause of death: A review.

Synthetic cannabinoids have caused a large number of emergency presentations to hospitals for adverse cardiovascular events including numerous deaths, particularly for the more potent analogs acting on the CB1 receptor. While smoked cannabis use is often associated with significant changes in heart rate and cardiac output, amongst other physiological changes, it has been rarely considered in the forensic literature as a significant contributory or causal factor in sudden unexpected death. A review of case reports of admissions to hospitals for cardiovascular events was undertaken together with a review of epidemiological studies, and case reports of sudden death attributed, at least in part, to use of this drug. These publications show that use of cannabis is not without its risks of occasional serious medical emergencies and sudden death, with reports of at least 35 persons presenting with significant cardiovascular emergencies who had recently smoked a cannabis preparation. At least 13 deaths from a cardiovascular mechanism have been reported from use of this drug which is very likely to be an under-estimate of the true incidence of its contribution to sudden death. In addition, many cases of stroke and vascular arteritis have also been reported with the latter often involving a limb amputation. While it is a drug with widespread usage among the community with relatively few deaths when faced with a circumstance of very recent use (within a few hours), a positive blood concentration of THC and a possible cardiac-related or cerebrovascular cause of death this drug should be considered, at least, a contributory cause of death in cases of sudden or unexpected death.