Near Real-time Determination of the Prevalence of Cannabinoids, Cathinones, and Synthetic Opioids

Unregulated new psychoactive substances (NPS) in “pure” or “preparation” forms are designed to mimic the effects of controlled substances, and are introduced and reintroduced in the market as a cheap substitute of established regulated drugs in quick succession to loophole the law enforcement efforts on combating drugs. For example, carfentanil, a synthetic opioid activates the opioid receptors similar to morphine but it is astoundingly potent compared to a typical drug of abuse (100 times more potent than fentanyl and 10,000 times more powerful than morphine). Based on the cost- and time-intensive forensic analysis, National Drug Early Warning System reported the a total of 632 identifications of NPS including 502 opioids/analgesics, 74 synthetic cannabinoids, 24 cathinone identifications in the second quarter of 2018 in the USA. The UPLC-MS/MS based analytical technique was developed capable of determining trace level NPS in wastewater. The cost-effective, comprehensive, and near-real-time approach, wastewater-based epidemiology, was used for the first time in the U.S. to determine the prevalence of 43 NPS in four U.S. communities. Methcathinone, 5-IT, MAB-CHMINACA, 4-methylamphetamine, 1-(3-chlorophenyl) piperazine (mCPP), 4-methyl pentedrone, 2-methyl-4’(methylthio)-2-morpholinopropiophenone, alpha-ethylaminohexanophenone, carfentanil, methoxyacetyl fentanyl, and valerylfentanyl were the most abundant NPS

Determination of Cannabinoids, Cathinones, and Synthetic Fentanyls Using Wastewater-Based Epidemiology

Unregulated new psychoactive substances (NPS) in “pure” or “preparation” forms are designed to mimic the effects of controlled substances, and are introduced and reintroduced in the market as a cheap substitute for established regulated drugs in quick succession to loophole the law enforcement efforts on combating drugs. For example, carfentanil, a synthetic opioid activates the opioid receptors similar to morphine but it is astoundingly potent compared to a typical drug of abuse (100 times more potent than fentanyl and 10,000 times more powerful than morphine). Based on the cost- and time-intensive forensic analysis, National Drug Early Warning System reported the fentanyl (3099), synthetic cathinones (670), and synthetic cannabinoids (633) counts of drug seizures in 2017 in Illinois by the law enforcement. The UPLC-MS/MS based analytical technique was developed capable of determining trace level NPS in wastewater. The cost-effective, comprehensive, and near-real-time approach, wastewater-based epidemiology, was used for the first time in the U.S. to determine the prevalence of 43 NPS in four U.S. communities. Methcathinone, 5-IT, 4-methylamphetamine, 1-(3-chlorophenyl) piperazine (mCPP), 4-methyl pentedrone, methoxyacetyl fentanyl, carfentanil, MAB-CHIMINACA, and 2-methyl-4’(methylthio)-2-morpholinopropiophenone were the most abundant NPS

Occurrence and Mass Loading of Synthetic Opioids, Synthetic Cathinones, and Synthetic Cannabinoids in Wastewater Treatment Plants in Four U.S. Communities

A few new psychoactive substances (NPS) that mimic the effects of controlled neuropsychiatric and illicit drugs have been forensically identified in the U.S. Wastewater-based epidemiology (WBE) can provide a comprehensive and more cost- and time-effective method of determining the prevalence of NPSs in communities. In this study, an analytical method capable of simultaneous determination of trace-level 40 NPS residues (synthetic opioids, synthetic cannabinoids, synthetic cathinones, piperazines, indole, and amphetamine) in wastewater was developed and validated. The developed analytical method was utilized to determine the occurrence of NPSs in four rural communities in southern Illinois. Nine NPSs (carfentanil, furanyl fentanyl, methoxyacetyl fentanyl, MAB-CHMINACA, methcathinone, 4-methyl pentedrone, 2-methyl-4′-(methylthio)-2-morpholinopropiophenone (MMMP), 1-(3-chlorophenyl) piperazine (mCPP), and 5-(2-Aminopropyl) Indole (5IT) were quantified. Methcathinone was the most frequently detected NPS (detection frequency, df = 100%) followed closely by the MMMP and mCPP (df = 91%). The mass loading of methcathinone, mCPP, and 5-IT using ammoniacal nitrogen-based population were up to 21.1 ± 1.3 mg/d/1000 people, 15.0 ± 0.5 mg/d/1000 people, and 9.75 ± 2.72 mg/d/1000 people, respectively. This is the first study to determine the occurrence of NPSs including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and piperazines in the U.S. communities

Estimation of the consumption of illicit drugs during special events in two communities in Western Kentucky, USA using sewage epidemiology

Sewage epidemiology is a cost-effective, comprehensive, and non-invasive technique capable of determining semi-real-time community usage of drugs utilizing the concentration of drug residues in wastewater, wastewater inflow, and the population size served by a wastewater treatment plant. In this study, semi-real-time consumption rates of ten illicit drugs were determined using sewage epidemiology during special events including Independence Day, the 2017 solar eclipse, and the first week of an academic semester in the Midwestern United States. The average per-capita consumption rate of amphetamine, methamphetamine, cocaine, and THC were significantly different between two similar-sized communities during Independence Day observation week (p \u3c 0.046) and a typical week (p \u3c 0.001). Compared to a typical day, the consumption rate of amphetamine, methamphetamine, cocaine, morphine, and methadone was significantly higher on Independence Day (p \u3c 0.021) and during solar eclipse observation (p = 0.020). The estimated percentage of the population that consumed cocaine in a community is similar to the conventionally estimated consumption of cocaine; however, the combined estimated population that consumed amphetamine and methamphetamine based on sewage epidemiology was ~2 to 4 fold higher than the conventional estimates. This study is the first to compare community use of drugs during special events in the USA using sewage epidemiology

Phthalate and non-phthalate plasticizers in indoor dust from childcare facilities, salons, and homes across the USA

The quality of indoor environment has received considerable attention owing to the declining outdoor human activities and the associated public health issues. The prolonged exposure of children in childcare facilities or the occupational exposure of adults to indoor environmental triggers can be a culprit of the pathophysiology of several commonly observed idiopathic syndromes. In this study, concentrations of potentially toxic plasticizers (phthalates as well as non-phthalates) were investigated in 28 dust samples collected from three different indoor environments across the USA. The mean concentrations of non-phthalate plasticizers [acetyl tri-n-butyl citrate (ATBC), di-(2-ethylhexyl) adipate (DEHA), and diisobutyl adipate (DIBA)] were found at 0.51e880 mg/g for the first time in indoor dust samples from childcare facilities, homes, and salons across the USA. The observed concentrations of these replacement non-phthalate plasticizer were as high as di-(2-ethylhexyl) phthalate, the most frequently detected phthalate plasticizer at highest concentration worldwide, in most of the indoor dust samples. The estimated daily intakes of total phthalates (n = 7) by children and toddlers through indoor dust in childcare facilities were 1.6 times higher than the non-phthalate plasticizers (n = 3), whereas estimated daily intake of total non-phthalates for all age groups at homes were 1.9 times higher than the phthalate plasticizers. This study reveals, for the first time, a more elevated (~3 folds) occupational intake of phthalate and non-phthalate plasticizers through the indoor dust at salons (214 and 285 ng/kg-bw/day, respectively) than at homes in the USA

Basketball and drugs: Wastewater-based epidemiological estimation of discharged drugs during basketball games in Kentucky

High school sports gather a significantly larger number of fans than college and professional sports in the U.S. Adolescent and adult students in high schools and colleges (aged 12–25) are among the most vulnerable population to substance use. Event planners, risk managers, and emergency medical service personnel can extrapolate the mass loads of drugs in wastewater in this study to evaluate the spectator behavior in relatively larger basketball gatherings. Thirty-three illicit and prescribed psychotic drug residues (out of target 36) and five new psychoactive substances (NPS, out of target 40) were quantified in wastewater, using ultra-performance liquid chromatography and tandem mass spectrometry, discharged during a college and a high school basketball games that were played in the same stadium in Kentucky. The wastewater concentrations of amphetamine, methylphenidate, hydromorphone were significantly higher (p ≤ 0.040) during a high school basketball game whereas cocaine, hydrocodone, and gabapentin was significantly higher (p ≤ 0.006) in a college basketball game. Higher cocaine to its metabolite ratio suggested that a significant amount of cocaine may have directly discharged down the drain during the college basketball game. Two synthetic cathinones (methcathinone and 4-methyl pentedrone) and three other NPSs (4-ANPP, mCPP, and 4-methylamphetamine) were also quantified in wastewater indicate the prevalence of NPSs in Kentucky. This is the first report of quantified substances of potential abuses at basketball games

Prevalence of illicit and prescribed neuropsychiatric drugs in three communities in Kentucky using wastewater-based epidemiology and Monte Carlo simulation for the estimation of associated uncertainties

A cost-effective alternative approach capable of determining the prevalence of substance use in communities can complement the existing efforts of combating drug abuse and addiction. In this study, the prevalence of 10 illicit and 19 prescribed psychoactive drugs of potential abuse was determined utilizing wastewater-based epidemiology, and compared in two adjoined urban communities and a rural community. This is the first application of the Monte Carlo simulation method to account multiple uncertainties and propagation of errors associated with the individual parameter of wastewater based epidemiological estimations in the U.S. A significantly higher prevalence of cocaine [3830 (mean difference, MD: 2960) mg/d/1000 people] was found in the central business district while the per-capita consumption rates of amphetamine [738 (MD: 338) mg/d/1000 people] and methamphetamine [1660 (MD: 629) mg/d/1000 people] were higher in a rural community. Among narcotics, the per-capita consumption rate of fentanyl and morphine was significantly higher in urban communities while codeine, hydrocodone, hydromorphone, and buprenorphine were dominant in a rural community. The significantly higher prevalence of buprenorphine (˜20-30 folds), oxycodone (˜2-3 folds), and alprazolam (˜2-3 folds) determined in these communities compared to the conventional estimates based on the electronically reported prescriptions and drug-related inpatient hospitalizations suggest the abuse of these drugs

Uncertainties Treatment for Wastewater-Based Epidemiological Estimation of the Consumption of Illicit and Prescribed Neuropsychiatric Drugs in Two Urban Communities in Kentucky Using Ammonium Normalized Population and Monte Carlo Simulation

The conventional estimation of the prevalence of substance use in a community based on self-reported surveys typically underestimates the actual consumption. Drug’s residues in raw wastewater collected from the centralized wastewater treatment plants were utilized – Wastewater-Based Epidemiology (WBE) – to determine the consumption rate of illicit and prescribed neuropsychiatric residues in two urban communities in eastern Kentucky and two rural communities in western Kentucky. The ammonical nitrogen content in raw wastewater samples was used to minimize the uncertainty associated with the population dynamicity. Uncertainties associated with the several WBE parameters to back-calculate the consumption rate of drugs such as flow rate measurement, pharmacokinetic data, population, and stability of drug residues in wastewater were evaluated using Monte Carlo simulation. Communities investigated in eastern Kentucky had ~10-fold larger population and ~2-fold higher per-capita income than in western Kentucky. Cocaine was the dominant illicit drug consumed in the eastern communities (~3-fold higher than in western communities) while methamphetamine controls the consumption profile in the western communities (2 folds higher than in eastern communities). However, venlafaxine and citalopram were the two major prescribed neuropsychiatric drugs consumed in all communities. While the opioid epidemic has been declared as a national public health emergency in the USA, codeine and hydrocodone were the most consumed prescription opioids

Mass loading and removal of pharmaceuticals and personal care products including psychoactives, antihypertensives, and antibiotics in two sewage treatment plants in Southern India

Environmental contamination by pharmaceuticals and personal care products (PPCPs) is barely studied in India despite being one of the largest global producers and consumers of pharmaceuticals. In this study, 29 pharmaceuticals and six metabolites were determined in sewage treatment plants (STPs) in Udupi (STPU: population served ~150,000) and Mangalore (STPM: population served ~450,000); the measured mean concentrations ranged from 12 to 61,000 ng/L and 5.0 to 31,000 ng/L, respectively. Atorvastatin (the most prescribed antihypercholesterolemic in India), mefenamic acid, and paraxanthine were found for the first time in wastewater in India at the mean concentrations of 395 ng/L, 1100 ng/L, and 13,000 ng/L, respectively. Select pharmaceutical metabolites (norverapamil and clopidogrel carboxylic acid) were found at concentrations of upto 7 times higher than their parent drugs in wastewater influent and effluent. This is the first study in India to report mass loading and emission of PPCPs and their select metabolites in STPs. The total mass load of all PPCPs analyzed in this study at STPU (4.97 g/d/1000 inhabitants) was 3.6 times higher than calculated for STPM. Select recalcitrant PPCPs (carbamazepine, diazepam, and clopidogrel) were found to have negative or no removal from STPU while additional treatment with upflow anaerobic sludge blanket reactor at STPM removed (up to 95%) these PPCPs from STPM. Overall, 5.1 kg of caffeine, 4.1 kg of atenolol, 2.7 kg of ibuprofen, and 1.9 kg of triclocarban were discharged annually from STPU. The PPCP contamination profile in the Indian STP was compared with a similar study in the USA

Hour-level Resolution on Consumption Pattern of Substance Abuse

Conventional survey-based approaches of determining the consumption statistics of drugs in communities are suffered from non-response biases, and typically underestimate the actual consumption. Time and cost-intensive conventional approaches, therefore, can’t be utilized to determine high-resolution temporal variability in drug consumption. In this study, the temporal trend of consumption of 10 illicit and 26 prescribed neuropsychiatric drugs was determined at hour-level resolution utilizing wastewater-based epidemiology. The hourly composite raw wastewater (every 10 minutes) samples were collected for three consecutive days in a typical week (total of 72 samples), analyzed for target drug residues using UPLC-MS/MS, and back-calculated the consumption rate of drugs in a community. Typical 24 h-composite samples and grab samples were also analyzed and compared to the hourly composite samples. Time-sensitive consumption pattern of drugs can be critical information for authorities to combat drug abuse and addiction