Automatic analytical approach for the determination of 12 illicit drugs and nicotine metabolites in wastewater using on-line SPE-UHPLC-MS/MS

In this study,we developed a novel on-line solid phase extraction(SPE)-ultra-high-performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS)-based analytical method for simultaneously quantifying 12 illicit drugs and metabolites(methamphetamine,amphetamine,morphine,codeine,6-monoacetylmorphine,benzoylecgonine,3,4-methylenedioxymethamphetamine,3,4-methylenedioxyamphetamine,cocaine,ketamine,norketamine,and methcathinone)and cotinine(COT)in wastewater samples.The analysis was performed by loading 2 m L of the sample onto an Oasis hydrophilic-lipophilic balance cartridge and using a cleanup step(5%methanol)to eliminate interference with a total run time of 13 min.The isotope-labeled internal standard method was used to quantify the target substances and correct for unavoidable losses and matrix effects during the on-line SPE process.Typical analytical characteristics used for method validation were sensitivity,linearity,precision,repeatability,recovery,and matrix effects.The limit of detection(LOD)and limit of quantification(LOQ)of each target were set at 0.20 ng/L and 0.50 ng/L,respectively.The linearity was between 0.5 ng/L and250 ng/L,except for that of COT.The intra-and inter-day precisions were<10.45%and 25.64%,respectively,and the relative recovery ranged from 83.74%to 162.26%.The method was used to analyze various wastewater samples from 33 cities in China,and the results were compared with the experimental results of identical samples analyzed using off-line SPE.The difference rate was between 19.91%and-20.44%,and the error range could be considered acceptable.These findings showed that on-line SPE is a suitable alternative to off-line SPE for the analysis of illicit drugs in samples.

Quantitative Structure-retention Relationship Study on the GC-MS Retention Time of Illicit Drugs

A quantitative structure-retention relationship（QSRR） study has been carried out on the gas chromatograph-mass spectrometry（GC-MS） system retention time（RT） of two sets of illicit drugs by using molecular structural descriptors.Heuristic method（HM） was utilized to construct the linear models.Appropriate models with low standard errors and high correlation coefficients were obtained（R2=0.9873,F=390.18 for data set 1 and R2=0.9881,F=749.13 for data set 2）.The results of leave-one-out cross validation showed good predictive ability of these proposed models（R c2v= 0.9812 and R c2v= 0.9824,respectively）.Each molecular descriptor in the two models was disputed to unfold the relationship between the molecular structures and RT.

Basin-scale exposure risk of psychiatric pharmaceuticals and illicit drugs in tap water in Eastern China

A total of twenty-three psychiatric pharmaceuticals and illicit drugs were analyzed in tap water covering seven basins in Eastern China.The residual concentrations of these substances were detected up to 22.4 ng L^(-1).Among the substances,benzodiazepines were more often detected with higher median concentrations than those of illicit drugs.Generally,the higher residual levels of psychoactive substances were detected in the upstream of the basins compared with the downstream.For example,the concentrations of diazepam,temazepam,and oxazepam in the downstream were much higher than those in the upstream in OJ.Among the basins,YH was the most polluted region.Exposure assessment indicated the median exposure doses of diazepam and temazepam were from 85 to 99 and 3.5e4.1 pg kg^(-1) bw d^(-1) in the basins,respectively.Benchmark quotient for the nine detected substances was calculated in each basin with the range from 0.0001 to 0.0389,indicating low risk in the tap water for human health under current concentrations.

Rapid Screening of Nine Illicit Drugs in Human Blood and Urine by Direct Analysis in Real‑Time Mass Spectrometry

We aimed to establish for the rapid detection of morphine,O6‑monoacetylmorphine,heroin,codeine,cocaine,methamphetamine,ketamine,methadone,and dolantin in human blood and urine by direct analysis in real‑time coupled with tandem mass spectrometry(DART‑MS/MS).These samples were extracted by acetonitrile‑methanol(V/V=4:1),using DART 12 Dip‑it automatic sampling system.They were injected at 400℃,and analyzed by positive ion and multiple reaction monitoring mode.The detection limits of morphine,O6‑Monoacetylmorphine,heroin,codeine,cocaine,methamphetamine,ketamine,methadone,and dolantin were 100,50,50,100,20,20,10,1,and 0.01 ng/mL,respectively.The practical cases contained methamphetamine,codeine,cocaine,and O6‑monoacetylmorphine were detected accurately and rapidly.The method has the advantages of high sensitivity and good accuracy.The sample processing is simple and can be analyzed in a short time.This method is suitable for the analysis of morphine,O6‑monoacetylmorphine,heroin,codeine,cocaine,methamphetamine,ketamine,methadone,and dolantin in some practical cases.

Analysis and Dynamics of Illicit Drug Use Described by Fractional Derivative with Mittag-Leffler Kernel

Illicit drug use is a significant problem that causes great material and moral losses and threatens the future of the society.For this reason,illicit drug use and related crimes are the most significant criminal cases examined by scientists.This paper aims at modeling the illegal drug use using the Atangana-Baleanu fractional derivative with Mittag-Leffler kernel.Also,in this work,the existence and uniqueness of solutions of the fractional-order Illicit drug use model are discussed via Picard-Lindelöf theorem which provides successive approximations using a convergent sequence.Then the stability analysis for both disease-free and endemic equilibrium states is conducted.A numerical scheme based on the known Adams-Bashforth method is designed in fractional form to approximate the novel Atangana-Baleanu fractional operator of order 0<a≤1.Finally,numerical simulation results based on different values of fractional order,which also serve as control parameter,are presented to justify the theoretical findings.

Dispersive liquid-liquid microextraction,an effective tool for the determination of synthetic cannabinoids in oral fluid by liquid chromatography-tandem mass spectrometry

In the present work,dispersive liquid-liquid microextraction(DLLME)was used to extract six synthetic cannabinoids(JWH-018,JWH-019,JWH-073,JWH-200,or WIN 55,225,JWH-250,and AM-694)from oral fluids.A rapid baseline separation of the analytes was achieved on a bidentate octadecyl silica hydride phase(Cogent Bidentate C18;4.6 mm×250 mm,4μm)maintained at 37℃,by eluting in isocratic conditions(water:acetonitrile(25:75,V/V)).Detection was performed using positive electrospray ionization-tandem mass spectrometry.The parameters affecting DLLME(pH and ionic strength of the aqueous phase,type and volume of the extractant and dispersive solvent,vortex and centrifugation time)were optimized for maximizing yields.In particular,using 0.5 mL of oral fluid,acetonitrile(1 mL),was identified as the best option,both as a solvent to precipitate proteins and as a dispersing solvent in the DLLME procedure.To select an extraction solvent,a low transition temperature mixture(LTTM;composed of sesamol and chlorine chloride with a molar ratio of 1:3)and dichloromethane were compared;the latter(100μL)was proved to be a better extractant,with recoveries ranging from 73%to 101%by vortexing for 2 min.The method was validated according to the guidelines of Food and Drug Administration bioanalytical methods:intra-day and inter-day precisions ranged between 4%and 18%depending on the spike level and analyte;limits of detection spanned from 2 to 18 ng/mL;matrixmatched calibration curves were characterized by determination coefficients greater than 0.9914.Finally,the extraction procedure was compared with previous methods and with innovative techniques,presenting superior reliability,rapidity,simplicity,inexpensiveness,and efficiency.

Addictive behaviors in liver transplant recipients: The real problem?

Liver transplantation(LT) is the gold standard treatment for end-stage liver disease. Whatever the primary indication of LT, substance abuse after surgery may decrease survival rates and quality of life. Prevalence of severe alcohol relapse is between 11 and 26%,and reduces life expectancy regardless of the primary indication of LT. Many patients on waiting lists for LT are smokers and this is a major risk factor for both malignant tumors and cardiovascular events post-surgery. The aim of this review is to describe psychoactive substance consumption after LT, and to assess the impact on liver transplant recipients. This review describes data about alcohol and illicit drug use by transplant recipients and suggests guidelines for behavior management after surgery. The presence of an addiction specialist in a LT team seems to be very important.

Analysis of Cocaine and Crack Cocaine via Thin Layer Chromatography Coupled to Easy Ambient Sonic-Spray Ionization Mass Spectrometry

Cocaine and crack cocaine are usually seized with a great diversity of adulterants, such as benzocaine, lidocaine, caffeine, and procaine. The forensic identification of cocaine in these drug mixtures is normally performed using colorimetric testing kits, but these tests may suffer from interferences providing false-positive or false-negatives. In this work, we describe the use of thin layer chromatography coupled to easy sonic-spray ambient ionization mass spectrometry (TLC/EASI-MS) for rapid and secure analysis of cocaine and crack cocaine. Fifteen cocaine samples were analyzed, and all of them revealed positive TLC/EASI-MS results for cocaine, but other drugs and adulterants were also detected such as lidocaine, caffeine, benzocaine, lactose, benzoylecgonine, and ecgonidine. False positives and false negatives, as judged by the TLC Rf values, were identified via on-spot characterization by EASI-MS. The TLC/EASI-MS combination seems therefore to provide an appropriate technique for secure forensic investigations of illicit drugs.

A quantitative analysis of socioeconomics of illicit drug use for improving targeted interventions in Hong Kong

Illicit drug use is a critical and challenging issue globally,but there is a lack of thorough understanding of the underlying mechanisms of drug use,which is essential for policy interventions,in many threatened places.This study aims to explore the socioeconomic determinants of drug use to support policy design in Hong Kong and other regions with similar issues.Multiple linear regression models and fixed-effects models are employed to examine the socioeconomic determinants of drug use based on the most comprehensive data on drug use and population in Hong Kong from 1991 to 2016.The estimates show that demographic and socioeconomic characteristics are important predictors of illicit drug use.The highest rate of drug use is observed for people aged between 20 and 30,as well as for those with primary education.Compared with males,the female drug use rate is 15(or 46)per 10,000 people lower for the newly(or previously)addicted cases.A 10%increase in monthly income is associated with a 14%drop in drug use rate at the district level.The average annual expenditure on drug use is USD 32.6 million in Hong Kong.Drug policies shall pay more attention to these at-risk groups,and shall consider more financial support to lower the drug use rates.

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,a-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.

The use of wastewater analysis in forensic intelligence:drug consumption comparison between Sydney and different European cities

Wastewater analysis offers objective and complementary information to illicit drug agencies by monitoring patterns of illicit drug consumption.In this study,wastewater samples from three different wastewater treatment plants in Sydney,Australia were collected in March 2016.Ten targeted drugs were analysed and temporal and geographical analyses were performed to obtain a better understanding of the type and amount of illicit drugs consumed in Sydney in comparison with similar studies conducted around Australia and in Europe.Among the targeted drugs,methamphetamine was consumed the most,followed by cocaine and 3,4-methylenedioxymethamphetamine(MDMA).Weekly patterns were observed where a peak during the weekend was present.The geographical analysis showed differences between the regions targeted.This observation may be related to socio-demographic aspects.The comparison of our study to other data sources from Australia showed a high consumption of methamphetamine in Sydney and Western Australia.The comparison between Sydney and different European cities revealed a difference in consumption,which is in line with traditional market indicators.The information obtained through wastewater analysis provides complementary information regarding illicit drug consumption,the size,and the evolution of the illicit drug market.This,ultimately,will assist authorities in making informed decisions.

Pulmonary hypertension in extremely low birth weight infants:characteristics and outcomes

Background:To determine the characteristics and outcomes of pulmonary arterial hypertension(PAH)in extremely low birth weight(ELBW)infants.Methods:A retrospective case-control study of all ELBW infants admitted to a level III neonatal intensive care unit(NICU)between January 1,2003 and December 31,2010.Results:During the study period,450 ELBW infants were admitted.6.4%(29/450)were diagnosed with PAH and were matched to 26 controls.The mean gestational age of infants with PAH and their controls were similar[24.5±1.3 vs.24.9±1.8 weeks(P=0.26)];however the cases were smaller at birth than were controls[640.7±119.5 vs.727.0±184.5 g(P=0.04)].The diagnosis of PAH was made at a mean postnatal age of 131.8±53.7 days.Infants with PAH had a higher rate of intrauterine exposure to illicit maternal drug use[12/29(41%)vs.1/25(4%);P=0.001],a longer duration of initial mechanical ventilation[74.9±28.3 vs.59.1±27.8 days;(P=0.04)],a higher incidence of severe BPD[23/29(79%)vs.13/26(50%);P=0.02],and a greater NICU mortality rate[12/29(41%)vs.4/26(15%);P=0.04].Conclusion:PAH in ELBW infants is associated with maternal illicit drug use in pregnancy,longer exposure to mechanical ventilation,severe bronchopulmonary dysplasia and a significant increase in early mortality.