Evaluation of pre-analysis loss of dependent drugs in wastewater: stability and binding assessments.

Wastewater analysis has the potential to provide objective and timely data on population drug consumption, but some crucial factors such as pre-analysis drug loss during sample storage and filtration could affect the accuracy and reliability of the method, and these uncertainties have yet to be fully assessed. This study was designed to evaluate analyte stability in wastewater stored under different conditions with the aim of optimizing the sample storage procedures for future studies. It also investigated whether there is significant analyte loss during filtration before sample extraction and storage after that. The studied substances and metabolites were: cotinine, cocaine and its metabolite benzoylecgonine, phenethylamines amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), opioids including codeine, methadone, 6-monoacetylmorphine (MAM) and morphine. In most situations, storing samples at 4 °C is sufficient to stabilize analytes for at least 2 weeks, and refrigeration is unnecessary during sample transportation within 3 days. However, additional measures need to be taken if unstable analytes such as cocaine and MAM are to be analyzed. No significant analyte loss was observed in the filtration process or in reconstituted extract stored at 4 °C or -20 °C for 2 weeks. By choosing stable analytes and proper storage conditions, wastewater analysis has the potential to provide accurate data for estimation of community drug use.

Marked decline in 3,4-methylenedioxymethamphetamine (MDMA) based on wastewater analysis.

OBJECTIVE: Recent reports in Europe suggest a decline in 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) use, but quantifiable and objective measurement is unavailable. The global extent of changes in MDMA and related stimulant use is also unclear. This study aims to quantify changes in MDMA use in Australia and determine whether these changes have been accompanied by differing amounts of other stimulant use. METHOD: We acquired information on recent use of MDMA and related illicit stimulants in Australia using the method of wastewater analysis. Untreated wastewater samples collected from three metropolitan treatment plants in Adelaide from May to July 2009 and the same months in 2010 were analyzed. Concentrations of MDMA, methamphetamine, and benzoylecgonine (a metabolite of cocaine) were determined using solid phase extraction-liquid chromatography- tandem mass spectrometry. Weekly consumed doses of MDMA, methamphetamine, and cocaine per 1,000 people were estimated. RESULTS: From 2009 to 2010, weekly consumption of MDMA decreased from mean of 4.52 (SEM = 0.74) doses/week per 1,000 people to 0.08 (0.01) doses/week per 1,000 people (p < .001); weekly consumption of methamphetamine increased from a mean of 48.35 (6.13) doses/week per 1,000 people to 68.13 (5.33) doses/week per 1,000 people (p < .05); and weekly consumed doses of cocaine did not significantly change. Local roadside saliva testing data also showed that the MDMA-positive test rate decreased from 0.30% to 0.05% and the methamphetamine-positive test rate increased from 1.43% to 1.52% during the past 2 years. CONCLUSIONS: This study shows a 50-fold decrease in consumed doses of MDMA with a rise in methamphetamine use in Australia over a 1-year period.

Population drug use in Australia: a wastewater analysis.

Accurate information on drug use in communities is essential if health, social and economic harms associated with illicit drug use are to be addressed efficiently. In most countries population drug use is estimated indirectly via surveys, medical presentations and police and custom seizures. All of these methods have at least some problems due to bias, small samples and/or long time delays between collecting the information and analysing the results. Recently the direct quantification of drug residues in wastewater has shown promise as a means of monitoring drug use in defined geographical areas. In this study we measured 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine and benzoylecgonine in sewage inflows in metropolitan and regional areas of Australia and compared these data with published European data. Cocaine use was small compared to European cities (p<0.001) but was compensated for by much greater consumption of methamphetamine (p<0.001) and MDMA (p<0.05). MDMA was more popular in regional areas (p<0.05) whereas methamphetamine and cocaine were mainly consumed in the city (p<0.05). Greater than 5-fold increases in MDMA use were detected on weekends (p<0.001). This approach has the potential to improve our understanding of drug use in populations and should be further developed to improve prevention and treatment programs.

Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational 'ecstasy' users.

AIMS: To improve our understanding of the pharmacology of 'ecstasy' in recreational environments; in particular, to describe the composition of ecstasy pills, patterns of ecstasy use and the relationship between dose of 3,4-methylendioxymethamphetamine (MDMA) and resulting plasma concentrations. DESIGN, SETTING AND PARTICIPANTS: A naturalistic observational study of 56 experienced 'ecstasy' users in recreational settings in Australia. MEASUREMENTS: Drug use patterns (number of pills consumed, other drugs consumed). drug content of pills and resultant plasma concentrations of MDMA and related drugs were assessed by gas chromatography/mass spectrometry (GC/MS). FINDINGS: Ecstasy pills generally contained MDMA, but this was often combined with other drugs such as 3,4-ethylendioxyethylamphetamine (MDEA) and methamphetamine. The dose of MDMA per pill ranged from 0 to 245 mg and users consumed from one-half to five pills, with the total dose consumed ranging up to 280 mg. Plasma concentrations of MDMA increased with number of pills consumed and cumulative MDMA dose. Use of larger numbers of pills was associated with extended exposure to the drug. CONCLUSIONS: MDMA is the major active drug in ecstasy pills, but there is a high degree of variation in doses. Use of multiple pills over the course of one session is common and results in a sustained increase in MDMA plasma concentrations over a number of hours. This is likely to lead to a much greater exposure of the brain to MDMA than would be predicted from controlled single-dose pharmacokinetic studies.

Inhalant deaths in South Australia: a 20-year retrospective autopsy study.

A 20-year retrospective study of inhalant deaths in South Australia, autopsied at Forensic Science SA, was undertaken from January 1983 to December 2002. Thirty-nine cases were identified from an autopsy pool of 18,880 cases, with a male to female ratio of 12:1. Sixty-four percent of the victims (N = 25) died during voluntary inhalation of volatile substances and 28% (N = 11) committed suicide utilizing a volatile substance or gas. The remaining 3 cases involved a workplace accident (N = 1) and 2 cases of autoerotic death where inhalants were being used to augment solitary sexual activity. The mean age of the 28 victims of accidental inhalant death of 21 years (range, 13-45 years) was considerably less than that of the 11 suicide victims of 31.5 years (range, 17-48 years). No homicides were found. Approximately one quarter of the victims were Aboriginal (N = 11), 10 of whom had died as a result of gasoline inhalation ("petrol sniffing"). Other common substances of abuse were aliphatic hydrocarbons such as butane. The study has shown that those most at risk for accidental or suicidal inhalant deaths were young males, with 92% of victims overall being male, and with 77% of victims being under 31 years of age. Gasoline inhalation remains a significant problem in Aboriginal communities in South Australia.

Plasma drug concentrations and physiological measures in 'dance party' participants.

The increasing use of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) in the setting of large dance parties ('raves') and clubs has been the source of some concern, because of potential acute adverse events, and because animal studies suggest that MDMA has the potential to damage brain serotonin (5-HT) neurons. However, it is not yet known whether MDMA, as used in the setting of dance parties, leads to plasma levels of MDMA that are associated with toxicity to 5-HT neurons in animals. The present study sought to address this question. Plasma MDMA concentrations, vital signs, and a variety of blood and urine measures were obtained prior to, and hours after, individuals attended a dance party. After the dance party, subjects were without clinical complaints, had measurable amounts of residual MDMA in plasma, and nearly half of the subjects also tested positive for methamphetamine, another amphetamine analog that has been shown to have 5-HT neurotoxic potential in animals. Plasma concentrations of MDMA did not correlate with self-reported use of 'ecstasy' and, in some subjects, overlapped with those that have been associated with 5-HT neurotoxicity in non-human primates. Additional subjects were likely to have had similar concentrations while at the dance party, when one considers the reported time of drug ingestion and the plasma half-life of MDMA in humans. Hematological and biochemical analyses were generally unremarkable. Moderate increases in blood pressure, heart rate and body temperature were observed in the subjects with the highest MDMA plasma concentrations. These findings are consistent with epidemiological findings that most people who use MDMA at dance parties do not develop serious clinical complications, and suggest that some of these individuals may be at risk for developing MDMA-induced toxicity to brain serotonin neurons.

Survival of massive gamma-hydroxybutyrate/1,4-butanediol overdose.

Gamma-hydroxybutyrate and its metabolic precursors gamma butyrolactone and 1,4-butanediol are widely used recreational drugs known to cause short periods of deep sedation with rapid recovery. We present a case of survival with good neurological outcome following massive ingestion in which the patient remained sedated for 14 h.

Fatalities associated with the use of gamma-hydroxybutyrate and its analogues in Australasia.

OBJECTIVE: To identify deaths in Australasia associated with overdose of gamma-hydroxybutyrate (GHB) and its precursors (gamma-butyrolactone and 1,4-butanediol). DESIGN: A retrospective search of medical and scientific information sources, as well as popular newsprint, for the period January 2000-August 2003, with formal clinical, toxicological and forensic evaluation of retrieved data. MAIN OUTCOME MEASURE: Death associated with forensic data implicating GHB or its analogues. RESULTS: Ten confirmed GHB-associated deaths were identified, with eight considered to be directly attributable to GHB. Only two of these eight cases were positive for ethanol toxicology. CONCLUSIONS: Our study supports the existing evidence that GHB overdose is associated with fatalities, and that fatal overdoses occur in the context of isolated use.

Gasoline exposure in motor vehicle accident fatalities.

Three cases are described in which deaths after motor vehicle accidents occurred as a result of positional asphyxia associated with exposure to gasoline. The deceased individuals were aged 16, 34, and 35 years, respectively (M:F = 1:2) and had all been in the back seat of motor vehicles involved in rollover accidents that had resulted in spilling of gasoline with contamination of the cabins. Major components of gasoline were detected in blood and tissues by headspace gas chromatography. Postmortem toxicologic investigations of such cases, which include analyses for volatile hydrocarbons, may therefore produce additional significant information.