Does the preparation for intravenous administration affect the composition of heroin injections? A controlled laboratory study.

AIMS: To study whether the preparation procedure, and its acidic and heating conditions, used by heroin users to prepare heroin for intravenous administration affects the final composition of the fluid to be injected. METHODS: Samples from different seizures of illegal heroin provided by the Norwegian police were prepared by adding water and ascorbic acid before heating under controlled conditions in the laboratory. Further, three seizures were prepared with different amounts of ascorbic or citric acid relative to their diacetylmorphine content. Pure diacetylmorphine base or salt was also submitted to the procedure applying two different heating intensities. The seizures and the final product after preparation were analysed for diacetylmorphine, 6-acetylmorphine and morphine using liquid chromatography with tandem mass spectrometry (LC-MS-MS). RESULTS: After preparation, a decrease of 19.8% (25th and 75th percentiles = -29.2 and -15.3) in the initial diacetylmorphine content was observed. Both the 6-acetylmorphine and morphine content increased but, due to their low content in the initial product, diacetylmorphine still represented 83.9% (25th and 75th percentiles = 77.3 and 88.0) of the sum of these three opioids in the final solution. The loss of water during preparation caused an increase in the concentration of diacetylmorphine, 6-acetylmorphine and morphine, depending on the heating intensity applied. The content of these opioids was affected by the quantity and type of acid added in relation to the heroin purity and the level of diacetylmorphine dissolved being proportional to the amount of ascorbic acid, but not citric acid, in the sample with high heroin purity. CONCLUSIONS: Preparation of heroin for intravenous injection appears to change the amount or concentration of diacetylmorphine and its active metabolites, 6-acetylmorphine and morphine in the final product, depending on heroin purity, amount and type of acid used or heating conditions. These circumstances can contribute to unintentional variations in the potency of the final injected solution, and therefore affect the outcome after injection.

The implementation of per-se limits for driving under the influence of benzodiazepines and related drugs: No increased risk for arrest during therapeutic use in Norway.

Objective: To investigate whether the use of recommended therapeutic doses of medicinal drugs has led to suspicion of driving under the influence of drugs (DUID) after implementation of legislative limits for illicit and medicinal drugs in 2012.Methods: Data from suspected drug-impaired drivers apprehended by the police from 2013 to 2015 were selected from the Norwegian Forensic Toxicology Database. The blood samples had been analyzed for benzodiazepines (BZDs), z-hypnotics, opioids, stimulants, certain hallucinogens, and alcohol. Drivers who tested positive for one BZD or a z-hypnotic only, were included in the study. Drug concentrations measured in their blood samples were compared to the maximal obtainable steady state concentrations if the drug had been used in accordance with the recommendations set by the Norwegian Directorate of Health.Results: BZDs or z-hypnotics were found in 10 248 samples, representing 59.6% of the total number of drivers arrested for suspected DUID (n = 17 201). Only one BZD or z-hypnotic with a blood drug concentration above the legislative limit was detected in 390 (2.3%) of the total number of samples. Clonazepam was the most frequently detected BZD (n = 4656), while as a single drug above the legislative limit, it was detected in only 3.6% (n = 168) of the clonazepam-positive blood samples. For drivers testing positive for only one z-hypnotic, drug concentrations above the legislative limit were found in 27% (n = 55) of the blood samples that tested positive for zolpidem and 12.4% (n = 53) of the samples that tested positive for zopiclone. In total, 155 subjects out of 10 248 testing positive for BZDs or z-hypnotics displayed concentrations above the legislative limit but within the concentration ranges that are expected when taking recommended therapeutic drug doses, and 77 below the legislativel limit.Conclusions: The results show that the implementation of legislative limits for BZDs and z-hypnotics may have contributed to DUID suspicion for a small group of patients using therapeutic drug doses; only 1.3% of the suspected DUID offenders had concentrations of only one of those drugs in-line with recommended therapeutic dosing.

An Experimental Study of Diazepam and Alprazolam Kinetics in Urine and Oral Fluid Following Single Oral Doses.

Benzodiazepines are commonly seen in samples submitted for drug testing of patients, people involved in child welfare cases, work-place drug testing, as well as in drug-facilitated assaults. Limited previous experimental studies are available regarding the excretion of benzodiazepines in urine and oral fluid. The aim of this study was to investigate the concentrations of diazepam and alprazolam in oral fluid and urine for up to 2 weeks after ingestion of a single oral dose in healthy volunteers. A total of 11 healthy volunteers ingested 10 mg diazepam at the start of the study and 0.5 mg alprazolam on Day 3 of the study. A total number of 10 oral fluid samples and 17 urine samples were collected from each participant. The samples were analyzed by liquid chromatography with tandem mass spectroscopy and ultra-high performance liquid chromatography tandem mass spectrometry methods. The median detection time was 252 h for the longest detected diazepam metabolite in urine (oxazepam, range 203-322) and 132 h in oral fluid (N-desmethyldiazepam, range 109-136). For alprazolam, the median detection time was 36 h (metabolite α-OH-alprazolam, range 26-61) in urine and 26 h (alprazolam, range 4-37) in oral fluid. These results show that detection times are only 36 h for alprazolam in urine after intake of a single therapeutic oral dose. For diazepam in urine, detection times were 11 days. Detection times were generally shorter in oral fluid compared to urine. The results could be helpful in the interpretation of diazepam or alprazolam findings in drug testing cases involving urine or oral fluid.

Comparative Study of Postmortem Concentrations of Antidepressants in Several Different Matrices.

Peripheral blood (PB) is considered to be the golden standard for measuring postmortem drug concentrations. In several cases, PB is however not available, but information regarding drug findings might still be crucial in order to determine the cause of death. Antidepressants are frequently detected in postmortem samples from forensic toxicology cases, but the literature investigating concentrations in other matrices than peripheral and heart blood is limited.We here describe a study for comparison of concentrations for a large number of different drugs in six different matrices. A total of 173 postmortem cases were included in the study material. The results from 44 cases with findings of antidepressants (amitriptyline/nortriptyline, citalopram, mianserin, mirtazapine, paroxetine, sertraline, trimipramine and venlafaxine) are presented in this article. Concentrations in peripheral and cardiac blood (CB), pericardial fluid (PF), two muscle samples and vitreous humour (VH) are compared. Ratios between concentrations in different matrices have also been compiled from available literature.All the investigated antidepressants were detected in all different matrices, and comparable concentration levels were found in the different matrices with a few exceptions. Concentrations in VH were generally lower than in the other matrices, and in a few cases with low concentrations in blood the antidepressants were not detected in VH. For most of the cases, ratios of 0.5-2 were found between concentration in PB and that in the other matrices. Some deviant concentrations where however found.This study shows that CB, PF, muscle and VH can provide important indications of the corresponding concentrations in PB when PB is not available.

Metabolites of Heroin in Several Different Post-mortem Matrices.

In some forensic autopsies blood is not available, and other matrices are sampled for toxicological analysis. The aims of the present study were to examine whether heroin metabolites can be detected in different post-mortem matrices, and investigate whether analyses in other matrices can give useful information about concentrations in peripheral blood. Effects of ethanol on the metabolism and distribution of heroin metabolites were also investigated. We included 45 forensic autopsies where morphine was detected in peripheral blood, concomitantly with 6-acetylmorphine (6-AM) detected in any matrix. Samples were collected from peripheral blood, cardiac blood, pericardial fluid, psoas muscle, lateral vastus muscle, vitreous humor and urine. Opioid analysis included 6-AM, morphine, codeine, and morphine glucuronides. The 6-AM was most often detected in urine (n = 39) and vitreous humor (n = 38). The median morphine concentration ratio relative to peripheral blood was 1.3 (range 0-3.6) for cardiac blood, 1.4 (range 0.07-5.3) for pericardial fluid, 1.2 (range 0-19.2) for psoas muscle, 1.1 (range 0-1.7) for lateral vastus muscle and 0.4 (range 0.2-3.2) for vitreous humor. The number of 6-AM positive cases was significantly higher (P = 0.03) in the ethanol positive group (n = 6; 86%) compared to the ethanol negative group (n = 14; 37%) in peripheral blood. The distribution of heroin metabolites to the different matrices was not significantly different between the ethanol positive and the ethanol negative group. This study shows that toxicological analyses of several matrices could be useful in heroin-related deaths. Urine and vitreous humor are superior for detection of 6-AM, while concentrations of morphine could be assessed from peripheral or cardiac blood, pericardial fluid, psoas muscle and lateral vastus muscle.

Quantitative method for analysis of six anticoagulant rodenticides in faeces, applied in a case with repeated samples from a dog.

BACKGROUND: Accidental poisoning with anticoagulant rodenticides is not uncommon in dogs, but few reports of the elimination kinetics and half-lives in this species have been published. Our objectives were to develop and validate a new method for the quantification of anticoagulant rodenticides in canine blood and faeces using reversed phase ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and apply the method on a case of anticoagulant rodenticide intoxication. RESULTS: Sample preparation was liquid-liquid extraction. Six anticoagulant rodenticides were separated using a UPLC® BEH C18-column with a mobile phase consisting of 5 mM ammonium formate buffer pH 10.2 and methanol. MS/MS detection was performed with positive electrospray ionization and two multiple reaction monitoring transitions. The limits of quantification were set at the levels of the lowest calibrator (1.5-2.7 ng/mL or ng/g). The method was successfully applied to a case from a dog accidentally poisoned with anticoagulant rodenticide. Coumatetralyl and brodifacoum concentrations were determined from serial blood and faecal samples. A terminal half-life of at least 81 days for coumatetralyl in blood was estimated, which is longer than previous reported in other species. A slow elimination of brodifacoum from the faeces was found, with traces still detectable in the faeces at day 513. CONCLUSIONS: This study offers a new method of detection and quantification of six frequently used anticoagulant rodenticides in canine faeces. Such drugs might cause serious health effects and it is important to be able to detect these drugs, to initiate proper treatment. The very long elimination half-lives detected in our study is important to be aware of in assessment of anticoagulant rodenticide burden to the environment.

The Appearance, Taste, and Concentrations of Zolpidem Dissolved in Still Water and Carbonated Beverages.

Zolpidem is a sedative that could be used to drug victims, but its suitability to dissolve in drinks is unknown. In this small study, we added either crushed or whole tablets of zolpidem hemitartrate to carbonated beverages or still water to observe how this affected the taste and appearance. Also, concentrations were measured by ultra-high performance liquid chromatography tandem mass spectrometry at different time intervals. Two crushed tablets (20 mg) in cider (250 mL) lead to a maximum concentration of 84 mg/L zolpidem base after 30 min, while the corresponding concentration after adding fifteen tablets (150 mg) was 467 mg/L. There was little change in taste, but froth and turbidity were observed when adding high doses to carbonated beverages. Carbonated beverages spiked with 20 mg of crushed zolpidem hemitartrate tablets reached concentrations that could cause impairment. Spiking with 150 mg could possibly be lethal if several mouthfuls were ingested.

Is Hair Analysis Useful in Postmortem Cases?

In postmortem cases, detection of drugs in blood is most relevant with regard to determining cause of death. However, it is sometimes also of interest to gain as much information as possible regarding the deceased's use of drugs in the period before death. The aim of this study was to compare results from analyses of a repertoire of psychoactive medicinal drugs in blood and hair samples from a larger material of postmortem cases. Hair samples in addition to blood were collected from 55 forensic autopsies and analyzed for a repertoire of 39 medicinal drugs (benzodiazepines, antidepressants and antipsychotics) using av fully validated liquid chromatography-tandem mass spectrometry method. In total, hair analyses gave information of the use of drugs not detected in blood in 47 of the 55 cases (85%). The most frequent single drugs detected in hair, but absent in blood, were benzodiazepines (64%), followed by antidepressants (35%). In each case, 1-10 (median two) single drugs were detected in hair, but absent in blood. In only two cases (4%), benzodiazepines were detected in blood and no benzodiazepines were detected in hair. In conclusion, hair analyses in addition to blood frequently indicate prior use of drugs that could yield important information about for instance unknown psychiatric diagnoses. In only a small number of cases lack of detections from the same drug class in hair might indicate reduced tolerance to drug effects.

Determination of Acetaminophen, Dexchlorpheniramine, Caffeine, Cotinine and Salicylic acid in 100 µL of Whole Blood by UHPLC-MS/MS.

A sensitive and robust ultra-high-performance liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of acetaminophen, dexchlorpheniramine, caffeine, cotinine and salicylic acid in postmortem blood samples from children younger than 4 years. The sample was prepared by a protein precipitation with ice-cold methanol/acetonitrile mixture (85:15, v/v). The organic phase was evaporated to dryness and the residue was dissolved in the mobile phase. Separation, with gradient elution and an acidic mobile phase, was achieved on an Acquity UPLC® HSS T3 column. The compounds were quantified using a multiple reaction-monitoring mode. Two transitions were monitored for each compound and one for the deuterated internal standards. The mass spectrometric detection in the positive ion mode was performed for all the compounds except salicylic acid which was detected in the negative ionization mode. The limits of quantification were as follows: acetaminophen 0.30 mg/L, dexchlorpheniramine 0.0050 mg/L, caffeine 0.099 mg/L, cotinine 0.00035 mg/L and salicylic acid 1.3 mg/L. Between-assay and within-assay precisions were ≤15% (biases: -10% to 26%) and ≤10%, respectively. Extraction recoveries varied from 93% to 137%. The matrix effects in blood, corrected with deuterated internal standards, were 100% ± 10% for all compounds except dexchlorpheniramine (111%) and caffeine (138%).

A literature review of blood concentrations of new psychoactive substances classified as phenethylamines, aminoindanes, arylalkylamines, arylcyclohexylamines, and indolalkylamines.

Interpretation of blood concentrations of new psychoactive substances (NPS) requires comparison of the results to previously published case reports; as only a few experimental studies for these substances exist. A large number of articles representing single or multiple cases have been published for a great number of substances, making a unified overview difficult. In this review we have collected all published blood concentrations from the NPS groups classified as phenethylamines, aminoindanes, arylalkylamines, arylcyclohexylamines, and indolalkylamines, and also included unpublished results for MPA, MXE, 4-FMA, 4-FA and 4-MA analyzed in our laboratory. In total, 71 publications on 35 different drugs were summarized. For most of the drugs, the total number of reported cases was very low (≤5). For some of the synthetic drugs, however, a higher number of blood concentrations are now available; especially for 5-IT (32 reported cases in total), MPA (31 reported cases in total) and MXE (36 reported cases in total), thus the published results are more substantial. The present compilation could be a helpful tool for forensic toxicologists when blood concentrations of NPS are assessed.

THC and CBD in blood samples and seizures in Norway: Does CBD affect THC-induced impairment in apprehended subjects?

BACKGROUND AND AIMS: Several publications have suggested increasing cannabis potency over the last decade, which, together with lower amounts of cannabidiol (CBD), could contribute to an increase in adverse effects after cannabis smoking. Naturalistic studies on tetrahydrocannabinol (THC) and CBD in blood samples are, however, missing. This study aimed to investigate the relationship between THC- and CBD concentrations in blood samples among cannabis users, and to compare cannabinoid concentrations with the outcome of a clinical test of impairment (CTI) and between traffic accidents and non-accident driving under the influence of drugs (DUID)-cases. Assessment of THC- and CBD contents in cannabis seizures was also included. METHODS: THC- and CBD concentrations in blood samples from subjects apprehended in Norway from April 2013-April 2015 were included (n=6134). A CTI result was compared with analytical findings in cases where only THC and/or CBD were detected (n=705). THC- and CBD content was measured in 41 cannabis seizures. RESULTS: Among THC-positive blood samples, 76% also tested positive for CBD. There was a strong correlation between THC- and CBD concentrations in blood samples (Pearson's r=0.714, p<0.0005). Subjects judged as impaired by a CTI had significantly higher THC- (p<0.001) and CBD (p=0.008) concentrations compared with not impaired subjects, but after multivariate analyses, impairment could only be related to THC concentration (p=0.004). Analyzing seizures revealed THC/CBD ratios of 2:1 for hashish and 200:1 for marijuana. CONCLUSIONS: More than ¾ of the blood samples testing positive for THC, among subjects apprehended in Norway, also tested positive for CBD, suggesting frequent consumption of high CBD cannabis products. The simultaneous presence of CBD in blood does, however, not appear to affect THC-induced impairment on a CTI. Seizure sample analysis did not reveal high potency cannabis products, and while CBD content appeared high in hashish, it was almost absent in marijuana.

Underestimated impact of novel psychoactive substances: laboratory confirmation of recreational drug toxicity in Oslo, Norway.

CONTEXT: Recreational drug toxicity is frequent. Availability of new psychoactive substances is steadily increasing. However, data with verified analyses from clinical settings are limited. To evaluate the impact of novel psychoactive substances (NPS) on recreational drug toxicity in Oslo, Norway, we analysed samples from a selection of patients. METHODS: All the patients presenting with recreational drug toxicity at the Oslo Accident and Emergency Outpatient Clinic (OAEOC) and at the Oslo University Hospital (OUH) were registered from April through September 2014. Oral fluid samples were collected at the OAEOC. Blood samples were collected at the OUH. The samples were screened using ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS). RESULTS: Nine hundred and sixty-four cases were included, 841 (87.2%) at the OAEOC and 123 (12.8%) at the OUH. A total of 55 oral fluid samples (OAEOC) and 103 blood samples (OUH) could be analysed. NPS were not clinically suspected in any of the screened cases. At the outpatient clinic, the most commonly found substances were clonazepam in 42/55 (76.4%) cases, amfetamines in 40/55 (72.7%) and heroin in 39/55 (70.9%). In seven (12.7%) cases NPS were detected: 4-methylamfetamine in three cases, dimethyltryptamine in two, methylone in one, and N,N-dimethyl-3,4-methylenedioxyamfetamine in one. Among the hospital patients, the most commonly found substances were clonazepam in 51/103 (49.5%) cases, amfetamines in 48/103 (46.6%), heroin in 31/103 (30.1%), and diazepam in 30/103 (29.1%). In five (4.9%) cases NPS were detected: JWH-210 in two cases, AM-2201 in two, and 5-EAPB in one. CONCLUSION: NPS were clinically not suspected, though found in eight percent of cases. Still, the vast majority of patients treated for recreational drug toxicity in Oslo have taken classical drugs. Management of these patients should be based on their clinical condition. However, it is highly important to be alert to atypical presentations possibly resulting from unsuspected drugs.

Blood concentrations of new designer benzodiazepines in forensic cases.

INTRODUCTION: A number of new designer benzodiazepines have reached the illegal drug market over the past years. Toxicological interpretation of concentrations of these drugs in blood is quite challenging as very limited human data have previously been published. The aim of this study was to report blood concentrations of new designer benzodiazepines in a population of drugged drivers as well as some other criminal offenders, and to relate this to clinical impairment. METHODS: The present material represents cases involving new designer benzodiazepines (clonazolam, diclazepam, flubromazepam, flubromazolam and pyrazolam) and etizolam, submitted for analyses during the period July 1, 2013-May 31, 2016. Analyses were performed using an ultra-performance liquid chromatography-tandem mass spectrometry method. Blood concentrations and results from the clinical test of impairment are reported. RESULTS: New designer benzodiazepines were detected in 77 cases during the study period. The median (range) concentrations were 0.012mg/L (0.00048-0.10) for flubromazolam (n=25), 0.055mg/L (0.0047-1.2) for flubromazepam (n=24), 0.013mg/L (0.0021-0.057) for diclazepam (n=15), 0.050mg/L (0.019-0.17) for etizolam (n=14), 0.0053mg/L (0.0019-0.011) for clonazolam (n=7) and 0.074mg/L for pyrazolam (n=1). In six cases, designer benzodiazepines were the only drugs detected in blood, and in two of those cases, the physician had given the conclusion of "considerably impaired" upon performing the clinical test for impairment. CONCLUSION: Given the lack of previously published data on human concentrations, results presented in this study could be helpful in interpretation of blood concentrations of new designer benzodiazepines. This is crucial for the assessment of the importance of toxicological results in suspected drugged drivers, rape victims, etc.

Novel psychoactive substances. / Nye psykoaktive stoffer.

There has been a significant increase in the number of new intoxicants on the illegal drugs market globally, also in Norway. The substances are given the name NPS: Novel Psychoactive Substances, and are mainly sold over the Internet. Uncertain dosage of potent substances entails a risk of accidental overdose, and therefore serious intoxication and death. In this article we provide an overview of current knowledge with regard to these substances.

Oral fluid drug analysis in the age of new psychoactive substances.

Oral fluid has become an important matrix for drugs of abuse analysis. These days the applicability is challenged by the fact that an increasing number of new psychoactive drugs are coming on the market. Synthetic cannabinoids and synthetic cathinones have been the main drug classes, but the diversity is increasing and other drugs like piperazines, phenethylamines, tryptamines, designer opioids and designer benzodiazepines are becoming more prevalent. Many of the substances are very potent, and low doses ingested will lead to low concentrations in biological media, including oral fluid. This review will highlight the phenomenon of new psychoactive substances and review methods for oral fluid drug testing analysis using on-site tests, immunoassays and chromatographic methods.

Codeine-spiked beer in a date rape case?

A case of suspected drug-facilitated sexual assault, involving codeine and acetaminophen, possibly mixed in beer, was recently addressed at the Norwegian Institute of Public Health. To examine the case, a small study was performed, spiking beer with preparations containing codeine and acetaminophen and observing the concentrations, appearance, and taste of the solutions. The study revealed the majority of the preparations to be quickly soluble in beer, achieving high concentrations, but at the expense of strong taste and drastic visible changes in the beer.

Comparison of drugs used by nightclub patrons and criminal offenders in Oslo, Norway.

The aim of this study was to investigate psychoactive drug use among nightclub patrons by analysing samples of oral fluid and compare with findings in blood samples from criminal suspects. We hypothesized that the profile of illicit drug use among nightclub patrons is different from what we observe in those forensic cases. Research stations were established outside nine popular nightclubs with different profiles and patron-characteristics in downtown Oslo. Data and sample collection was conducted on Fridays and Saturdays in March and May 2014. Individuals and groups who entered defined recruitment zones from 23:00 to 03:30 were invited to participate in this voluntary and anonymous study. Oral fluid was collected using the Intercept Oral Fluid Sampling Device. Methanol was added to increase the recovery of cannabinoids from the device. Sample preparation was performed using liquid-liquid extraction with ethyl acetate/heptane (4:1) after adding internal standards, ammonium carbonate buffer pH 9.3 and Triton X100. The first 80 samples were analysed for 122 substances, which included psychoactive medicinal drugs, classical illicit drugs and new psychoactive substances (NPS). Based on the findings and discussions with police and customs authorities, the remaining oral fluid samples were analysed for 46 substances. Among the 500 samples collected during the study period, we found illicit drugs in 25.4% and medicinal drugs in 4.2% of the samples. The most prevalent substances were: cocaine 14.6%, THC 12.4%, amphetamine/methamphetamine 2.8%, diazepam 1.2% and clonazepam 1.0%. Various NPS were found in 1.4% of the samples. The prevalence of drugs in blood samples from criminal suspects were for cocaine 3.4%, THC 34.7%, amphetamine/methamphetamine 37.0%, diazepam 12.0%, and clonazepam 29.3%. Multi-drug use was more common among criminal suspects (41.3%) than among club patrons (6.8%). The results showed that the drug use pattern among nightclub patrons was substantially different from the drug use pattern manifested by individuals apprehended by the police suspected for criminal conduct.

Determination of a selection of synthetic cannabinoids and metabolites in urine by UHPSFC-MS/MS and by UHPLC-MS/MS.

Two different analytical techniques, ultra-high performance supercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MS/MS) and reversed phase ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), were used for the determination of two synthetic cannabinoids and eleven metabolites in urine; AM-2201 N-4-OH-pentyl, AM-2233, JWH-018 N-5-OH-pentyl, JWH-018 N-pentanoic acid, JWH-073 N-4-OH-butyl, JWH-073 N-butanoic acid, JWH-122 N-5-OH-pentyl, MAM-2201, MAM-2201 N-4-OH-pentyl, RCS-4 N-5-OH-pentyl, UR-144 degradant N-pentanoic acid, UR-144 N-4-OH-pentyl, and UR-144 N-pentanoic acid. Sample preparation included a liquid-liquid extraction after deconjugation with ß-glucuronidase. The UHPSFC-MS/MS method used an Acquity UPC(2 TM) BEH column with a mobile phase consisting of CO2 and 0.3% ammonia in methanol, while the UHPLC-MS/MS method used an Acquity UPLC® BEH C18 column with a mobile phase consisting of 5 mM ammonium formate (pH 10.2) and methanol. MS/MS detection was performed with positive electrospray ionization and two multiple reaction monitoring transitions. Deuterated internal standards were used for six of the compounds. Limits of quantification (LOQs) were between 0.04 and 0.4 µg/L. Between-day relative standard deviations at concentrations ≥ LOQ were ≤20%, with biases within ±19%. Recoveries ranged from 40 to 90%. Corrected matrix effects were within 100 ± 10%, except for MAM-2201 with UHPSFC-MS/MS, and for UR-144 N-pentanoic acid and MAM-2201 N-4-OH-pentyl with UHPLC-MS/MS. Elution order obtained by UHPSFC-MS/MS was almost opposite to that obtained by UHPLC-MS/MS, making this instrument setup an interesting combination for screening and confirmation analyses in forensic cases. The UHPLC-MS/MS method has, since August 2014, been successfully used for confirmation of synthetic cannabinoids in urine samples revealing a positive immunoassay screening result. Copyright © 2015 John Wiley & Sons, Ltd.

Methiopropamine in blood samples from drivers suspected of being under the influence of drugs.

OBJECTIVES: Methiopropamine (MPA; 1-(thiophen-2-yl)-2-methylaminopropane) belongs to the new psychoactive substances (NPS) that have emerged on the drug market in recent years. MPA appeared in 2011 and is an analogue of methamphetamine, sold as, for example, "Slush Eric" and "Blow." It is reported to have effects similar to those of methamphetamine, but the toxicity in humans is not known. Three fatal cases involving MPA have been reported. One analytical confirmed intoxication case has been published, and this supports the symptoms described by the users. The prevalence of recreational use of MPA is unknown, and no studies have reported the prevalence in driving under the influence of drug (DUID) cases. METHODS: We investigated the frequency of MPA in DUID cases received at our institute during a 12-week period and report the analytical method using an ultraperformance liquid chromatography.tandem mass spectrometry for quantification of MPA in whole blood. The analytical findings were compared to the results from a clinical test of impairment performed by a physician shortly after the driving episode. The samples were analyzed for 42 different psychoactive substances. RESULTS: MPA was detected in 10 DUID cases (0.8% of the cases), only from male drivers. Other drugs were detected concomitantly in all the cases. Two of the cases were traffic accidents. CONCLUSIONS: Our study shows that MPA is found in DUID cases and reveals that NPS are used among drivers and also proven in blood from drivers involved in traffic accidents. More studies are requested regarding the pharmacological and toxicological effects of MPA and other NPS. This is the first article that describes a method for analyzing and quantifying MPA in whole blood samples.