Amphetamine Concentrations Research Articles

Contribution of methamphetamine and insulin to the death of a woman suffering from type I diabetes - which played the greater role?

This report presents a fatal case of a young female Type I diabetic patient who developed convulsions and loss of consciousness after taking methamphetamine and spending some time in a dance club. During the convulsions, she was given sugar and when no response occurred, her boyfriend who was not experienced in the use of insulin administered a dose of insulin to her. The woman lost consciousness and died despite the efforts of the emergency service. A biochemical analysis revealed a high level of insulin (196.67 mU/L) and low levels of glucose (2.96 mmol/L) and C-peptide (26 pmol/L). Toxicological analysis revealed a methamphetamine concentration of 389 ng/mL and an amphetamine concentration of 19 ng/mL. The forensic perspective of the difficult determination of the contribution of each of the factors to the death, i.e., the pre-existing medical condition (Type I diabetes), the use of methamphetamine, the physical exertion at the dance club, and, finally, the non-indicated administration of insulin, is discussed. The ruling of the court is also reported.

Alternative routine for reporting chiral amphetamine test results in assessment of attention-deficit/hyperactivity disorder medication: experiences from 2013 to 2023.

This study evaluated an alternative routine for reporting urinary chiral amphetamine results in assessment of attention-deficit/hyperactivity disorder (ADHD) treatment with amphetamine medications and for detecting side-use of illicit racemic amphetamine. Currently in Sweden, only enantiopure d-amphetamine-based ADHD medications (lisdexamphetamine dimesylate and dexamphetamine sulfate) are approved. It is therefore unsuitable to express the chiral result as the l/d-ratio, as before, because l-amphetamine should not be present provided treatment compliance. A new routine for LC-MS/MS chiral amphetamine testing was therefore introduced in 2020, whereby the relative proportion (%) of l-amphetamine and the total amphetamine and creatinine concentrations are reported. Evaluation of the new routine on 24,354 results from 2013 to 2023 revealed that it was useful to distinguish ADHD medication adherence from illicit drug use as the source for a positive test. The l-amphetamine proportion also reflected the enantiomeric content of the medications used. Overall, most results confirmed adherence to ADHD medication, as the l-amphetamine percentage was <1% in 76% of samples (2023) which is the recommended cutoff with enantiopure d-amphetamine medications. However, in all years, illicit drug use was indicated (>40% l-amphetamine) in 8.3%-14.5% of cases. In conclusion, this study demonstrated the clinical value and utility of a new routine for reporting urinary chiral amphetamine results to differentiate adherence to ADHD medication from illicit drug use. Unlike the l/d-amphetamine ratio, it considers differences in total amphetamine concentration and urine dilution, factors that can affect the interpretation.

Challenges and insights: Methamphetamine analysis in post-mortem putrefied human tissues in a hot climate

BackgroundThe production and distribution of methamphetamine (meth) is often associated with illegal and clandestine laboratories, posing significant challenges for law enforcement and public health efforts. Global concern is growing over meth-related fatalities, as its high potential for abuse and detrimental impact on health make it an important issue in the realm of substance abuse and addiction. This concern has notably increased in Saudi Arabia, where the hot climate adds complexity to the analysis due to challenges posed by putrefaction. There is still an urgent need to enhance the screening capabilities of many toxicology laboratories to determine the cause of death, whether it be due to drug use or natural causes. AimThis research aimed to investigate meth concentrations in post-mortem putrefied human solid tissues in a hot climate and comparing meth metabolite concentrations in cases where signs of putrefaction were observed versus those with no signs of putrefaction. The objective is to assist criminal investigations by analyzing meth and its metabolite concentrations. MethodsThis retrospective cohort study involved postmortem samples from human subjects during autopsies conducted between 2016 and 2022. It focused on analyzing meth and its metabolite concentrations using LC-MS/MS analysis. Data on demographics, medical history, age, location, putrefaction, and other drug use were retrieved from medical records. ResultsOut of the 27 reported samples of meth and its metabolite amphetamine in both putrefied and non-putrefied biological fluids and tissues, only 8 (30%) exhibited signs of putrefaction between 2016 and 2022. Despite decomposition, detectable concentrations of meth and amphetamine were sufficient to determine the cause of death and the source of amphetamines. ConclusionThis study found no significant difference in concentrations between putrefied and non-putrefied cases, underscoring the importance of multiple sample testing during autopsy for accurate interpretation. Each case is unique and must be considered individually.

Protective effects of amphetamine and methylphenidate against dopaminergic neurotoxicants in SH-SY5Y cells

Full treatment of the second most common neurodegenerative disorder, Parkinson’s disease (PD), is still considered an unmet need. As the psychostimulants, amphetamine (AMPH) and methylphenidate (MPH), were shown to be neuroprotective against stroke and other neuronal injury diseases, this study aimed to evaluate their neuroprotective potential against two dopaminergic neurotoxicants, 6-hydroxydopamine (6-OHDA) and paraquat (PQ), in differentiated human dopaminergic SH-SY5Y cells.Neither cytotoxicity nor mitochondrial membrane potential changes were seen following a 24-hour exposure to either therapeutic concentration of AMPH or MPH (0.001–10 μM). On the other hand, a 24-hour exposure to 6-OHDA (31.25–500 μM) or PQ (100–5000 μM) induced concentration-dependent mitochondrial dysfunction, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and lysosomal damage, evaluated by the neutral red uptake assay. The lethal concentrations 25 and 50 retrieved from the concentration-toxicity curves in the MTT assay were 99.9 µM and 133.6 µM for 6-OHDA, or 422 µM and 585.8 µM for PQ. Both toxicants caused mitochondrial membrane potential depolarization, but only 6-OHDA increased reactive oxygen species (ROS). Most importantly, PQ-induced toxicity was partially prevented by 1 μM of AMPH or MPH. Nonetheless, neither AMPH nor MPH could prevent 6-OHDA toxicity in this experimental model.According to these findings, AMPH and MPH may provide some neuroprotection against PQ-induced neurotoxicity, but further investigation is required to determine the exact mechanism underlying this protection.

Postmortem redistribution of amphetamines and benzodiazepines in humans: Important variables that might be influencing the central blood / peripheral blood ratio

IntroductionThe primary objective of postmortem forensic toxicology is to determine if toxicological substances detected in bodily material of victims have contributed to the death of the victim. Interpretation of postmortem drug concentrations is hindered by the fact that time and site dependent variations in postmortem drug concentrations occur, as a result of postmortem redistribution (PMR). An often-used marker for the occurrence of PMR, is the cardiac blood concentration/peripheral blood concentration ratio (C/P ratio) of a drug. In this study, we investigated the relationship between 13 variables and the C/P ratios of amphetamines and benzodiazepines. MethodToxicological results of all postmortem cases that were positive for amphetamines (amphetamine, MDMA, MDA) and/or benzodiazepines (diazepam, desmethyldiazepam, temazepam, oxazepam, midazolam, α-hydroxymidazolam) investigated by the Netherlands Forensic Institute between January 1 2010 and July 31 2020 were reviewed. A total of 112 amphetamine positive cases (224 paired specimen) and 179 benzodiazepine positive cases (358 paired specimen) were selected. The C/P ratios were determined for all selected cases. Ratios were compared between subgroups by performing either a Mann-Whitney U test or a Kruskal-Wallis test followed by post-hoc Mann-Whitney U test. ResultsAfter dividing cases in quartiles based on their amphetamine concentration in femoral blood, the amphetamine C/P ratio was significantly lower in cases with a high amphetamine concentration (quartile 4) compared to cases with a low amphetamine concentration (quartiles 1 and 2) with median C/P ratios of 1.6, 2.4 and 2.2, respectively (p-value<0.001 and p-value=0.001, respectively).The MDA C/P ratio was significantly higher in cases where trauma was the cause of death compared to cases where intoxication was the cause of death with median C/P ratios of 3.3 and 1.6, respectively (p-value<0.001). The MDA C/P ratio was also significantly lower in cases where resuscitation was attempted compared to cases where no resuscitation was attempted with median C/P ratios of 1.6 and 2.4, respectively (p-value=0.003). However, a significant dependency between the variables cause of death and attempted resuscitation was observed.No significant differences in benzodiazepine C/P ratios were observed between subgroups of any of the investigated variables. However, the low p-value of BMI suggests a potential difference in midazolam C/P ratio between BMI subgroups (p-value=0.027). ConclusionWhen interpreting postmortem toxicological results, it might prove useful to take the above-mentioned variables into account.

Uncertainty Evaluation for the Quantification of Urinary Amphetamine and 4-Hydroxyamphetamine Using Liquid Chromatography-Tandem Mass Spectrometry: Comparison of the Guide to the Expression of Uncertainty in Measurement Approach and the Monte Carlo Method with R.

Estimating the measurement uncertainty (MU) is becoming increasingly mandatory in analytical toxicology. This study evaluates the uncertainty in the quantitative determination of urinary amphetamine (AP) and 4-hydroxyamphetamine (4HA) using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method based on the dilute-and-shoot approach. Urine sample dilution, preparation of calibrators, calibration curve, and method repeatability were identified as the sources of uncertainty. To evaluate the MU, the Guide to the Expression of Uncertainty in Measurement (GUM) approach and the Monte Carlo method (MCM) were compared using the R programming language. The MCM afforded a smaller coverage interval for both AP (94.83, 104.74) and 4HA (10.52, 12.14) than that produced by the GUM (AP (92.06, 107.41) and 4HA (10.21, 12.45)). The GUM approach offers an underestimated coverage interval for Type A evaluation, whereas the MCM provides an exact coverage interval under an abnormal probability distribution of the measurand. The MCM is useful in complex settings where the measurand is combined with numerous distributions because it is generated from the uncertainties of input quantities based on the propagation of the distribution. Therefore, the MCM is more practical than the GUM for evaluating the MU of urinary AP and 4HA concentrations using LC-MS/MS.

Detection of methamphetamine in mouse femurs exposed to high temperature.

Bone samples are valuable for examining the cause of death and circumstance leading up to death when body fluids are not available for forensic toxicological analysis. Examined were heat-induced changes in methamphetamine and amphetamine concentrations in femurs removed from methamphetamine-injected mice to determine if the burned bones could be used for toxicology testing. The femurs were heated at 100°C, 300°C, or 500°C for 10 or 30 min. The tissue structure of the heated femurs was preserved at 100°C for 30 min but was destructed at higher temperatures. Methamphetamine and amphetamine were detected in femurs heated at 100°C for 10 min, 100°C for 30 min, and 300°C for 10 min (with methamphetamine and amphetamine concentrations ranging from 0.36 to 35 μg/g and 0.54 to 47 μg/g, respectively). Methamphetamine and amphetamine were detectable when heated above their decomposition temperature as a result of limited heat transfer do to protection provide by the femoral muscle. Thus, the bone could be a useful analytical sample in cases of burn-related deaths, where it is difficult to collect body fluids.

Nystagmus among suspected amphetamine impaired drivers

Clinical signs of drug use can be helpful to identify which drug has been consumed. Amphetamine intake has traditionally not been considered to cause nystagmus. The aim of this study was to explore whether there is a relationship between amphetamine use and nystagmus in a population of apprehended drivers in a naturalistic setting. We evaluated drivers suspected of drug-impaired driving where blood samples were collected and a clinical test of impairment (CTI) was performed. Evaluation of nystagmus is one of the CTI subtests. The samples were analysed for alcohol and psychoactive drugs. Cases with a nystagmus test were recorded and amphetamine-only cases were compared with alcohol-only cases and with cases where alcohol or drugs were not detected, respectively. Samples from 507 amphetamine-only cases were compared to 485 alcohol-only cases and 205 drug-negative cases. The median blood amphetamine concentration was 0.37 mg/L and the median alcohol concentration was 1.57 g/kg. The proportion of cases with nystagmus was similar in amphetamine-only cases (21%) and drug-negative controls (25%), p = 0.273, but higher in alcohol-only cases (53%), p < 0.001. No association was found between the blood amphetamine concentration and degree of nystagmus (Spearman's ρ = 0.008, p = 0.860), whereas an association between blood alcohol concentration and degree of nystagmus was demonstrated (ρ = 0.249, p < 0.001). In conclusion, our study did not find that apprehended drivers using amphetamine had more frequently nystagmus than a control group that tested negative for alcohol and drugs, even at high amphetamine concentrations in blood. Hence, nystagmus should not be considered a tool for identifying amphetamine-induced impairment in drivers.

Crash-involved THC-positive drivers in Norway have a high frequency of polysubstance use

BackgroundTetrahydrocannabinol (THC) is the most frequently detected drug in blood samples from apprehended drug driving suspects in Norway. This investigation aimed to study the extent of polysubstance use among apprehended crash-involved drivers with THC concentrations above the legal limit and explore the importance of THC in polysubstance cases. MethodsWe selected all drug driving cases where blood samples had been submitted for forensic toxicology testing after involvement in road traffic crashes during 2013–2020, except drivers who were fatally injured. ResultsTwenty percent (n = 2133) of the 10,520 apprehended crash-involved drivers had concentrations of THC in their blood above the legal limit of 1.3 ng/mL, and 84 % of those also had concentrations of alcohol or other drugs above the legal limits; 61 % for sedatives, 38 % for stimulants, 33 % for alcohol, and 10 % for opioids. The most frequent substance combination was cannabis together with sedatives and stimulants (22.9 %; n = 488). Polysubstance use was least common among drivers under 24 years. The proportion of drivers with THC > 5 ng/mL was highest if the blood sample was collected within 90 min after the crash, and when only THC was detected. There was a statistically significant inverse association between THC > 5 ng/mL and concentrations of alcohol or amphetamines at the highest sanction level. ConclusionsMost apprehended crash-involved THC-positive drivers also tested positive for other psychoactive substances. Drivers with high blood THC concentrations had less often high concentrations of other substances; cannabis might then have been a more important contributor to impairment.

Influence of fecal microbial transplant (FMT) between male and female rats on methamphetamine-induced hyperthermia

Objective To investigate the effect of bidirectional fecal microbial transplant (FMT) between male and female rats on methamphetamine (MA)-induced hyperthermia. Methods FMT was performed between male and female rats prior to MA (10 mg/kg, sc) treatment. Core body temperature, plasma drug and norepinephrine (NE) levels were measured and compared between treatment groups. 16S rRNA gene sequencing of bacterial communities between male and female rats was performed. Results MA treatment resulted in significantly higher core body temperatures in male groups (control and FMT-treated) compared to MA-treated female groups (control and FMT-treated). Plasma concentrations of MA and amphetamine were higher in females than males. Whereas, plasma norepinephrine (NE) levels were not different between male and female rats 90 minutes after MA treatment. At the phyla level, the microbiome of male and female control rats were dominated by Firmicutes and Bacteroidetes. Males had a higher relative abundance of Firmicutes and lower relative abundances of Bacteroidetes than females. The FMT procedure changed the recipient group towards their donor with males getting closer to their donors than females. In the control groups following MA treatment, Firmicutes increased and Bacteroides decreased in females and males. Conversely, in the FMT treatment groups following MA treatment, Firmicutes decreased while Bacteroidetes increased in females and males. Conclusions Although definite differences in the structure and diversity of the gut microbiome were observed using 16S rRNA gene sequencing of bacterial communities between male and female rats, these differences do not seem to contribute to the sex-based differences in MA-induced hyperthermia.

Detection of lisdexamfetamine and its metabolite d-amphetamine in urine and gastric contents collected from a cadaver at forensic autopsy

PurposeLisdexamfetamine (LDX), which is used for the treatment of attention-deficit/hyperactivity disorder and narcolepsy, is composed of l-lysine attached to dextroamphetamine (d-amphetamine). In this article, we report a forensic autopsy case in which prescription drugs were unknown at autopsy. While amphetamine was detected, methamphetamine could not be detected by liquid chromatography–tandem mass spectrometry (LC–MS/MS) in any of samples collected. Thus, we aimed to quantify LDX concentrations in autopsy samples and to prove that the amphetamine detected in this case was due to metabolized LDX.MethodsFemoral vein blood, cardiac whole blood, urine, and gastric content samples were taken at autopsy for toxicological analysis. Qualitative and quantitative analyses were performed using LC–MS/MS. In addition, optical isomer separation for the amphetamine detected was conducted. The stability of LDX in whole blood and urine was also examined at three different temperatures.ResultsThe concentrations of LDX were < 4.00, 30.9, and 4.42 ng/mL in whole blood, urine, and gastric content samples, respectively. The concentrations of amphetamine were 329, 510, 2970, and 915 ng/mL in femoral vein blood, heart whole blood, urine, and gastric contents, respectively. The amphetamine detected in this case was identified to be only d-amphetamine by optical isomer separation. The d-amphetamine detected was considered to be derived from LDX. Stability experiments revealed that LDX in whole blood decreased at ambient temperature.ConclusionsThe results in the present case report may be useful in interpreting whether or not the amphetamine detected in a cadaver is a metabolite of LDX.

A Case of Amphetamine and Methamphetamine Intoxication in Cat.

Stimulants belonging to the amphetamine group nowadays pose an undeniable worldwide threat to the life and health of users. Intoxications of domestic animals also occur, which can either be accidental or related to intentional human action. This study presents the first ever reported case of a simultaneous amphetamine and methamphetamine intoxication of a cat, along with the results of toxicological studies. Blood, urine, vitreous humor and liver were collected during the cat's autopsy and analyzed by UHPLC─QqQ─MS/MS. The sample preparation technique was based on one-step precipitation of proteins with cold acetonitrile. The determined amphetamine concentrations in the collected biological materials were 93.4 ng/mL in blood, 496.6 ng/mL in urine, 589.2 ng/mL in the vitreous humor and 291.2 ng/g in liver, respectively. Methamphetamine concentrations were 45.5 ng/mL in blood, 263.1 ng/mL in urine, 351.2 ng/mL in vitreous humor, and 97.7 ng/g in liver. Other substances were also found in the biological material, i.e., diazepam, oxazepam and nordiazepam. Cases of intentional or accidental poisoning of pets with psychoactive substances are a serious problem, carrying the risk to the health and life of the animal. Therefore, it is important to increase awareness of the high risk of poisoning of domestic animals, as well as to learn about the incompletely understood mechanisms of pharmacokinetics of various drugs in animals, including cats.

Nystagmus among amphetamine-impaired drivers

Clinical signs of drug use can be helpful to identify which drug has been used. Amphetamine intake has traditionally not been considered to cause nystagmus; however, there is a lack of evidence for this claim. The aim of this study was to find a relationship between amphetamine use and nystagmus in a population of apprehended drivers. We evaluated cases of drivers suspected of drugged driving where blood samples were collected and a clinical test of impairment (CTI) was performed. Evaluation of nystagmus is one of the CTI subtests. The samples were analysed for alcohol and psychoactive drugs. Cases with nystagmus were recorded and amphetamine-only cases were compared with alcohol-only cases and with cases where alcohol or drugs were not detected, respectively. Samples from 509 amphetamine-only cases were compared to 519 alcohol-only cases and 205 drug negative cases. The mean blood amphetamine concentration was 0.533 mg/L (range 0.027–3.650 mg/L) and the mean alcohol concentration was 1.57 g/kg (range 0.05–3.97 g/kg). The number of cases with nystagmus was similar in amphetamine-only cases (21%) and drug-negative controls (25%), P = 0.273. The number of cases with nystagmus was higher in alcohol-only cases (53%), than in amphetamine-only cases (21%), P < 0.001, and drug-negative controls (25%), P < 0.001. No association was found between the blood amphetamine concentration and nystagmus, whereas an association between blood alcohol concentration and nystagmus was demonstrated (Pearson's r = 0.252, P = 0.01). In our study, we did not find that apprehended drivers using amphetamine had more frequently nystagmus than a control group that tested negative for alcohol and drugs. One implication is that nystagmus is not a sensitive test to identify amphetamine-induced impairment.

Occurrence, distribution, and ecological risk of psychoactive substances in typical lakes and rivers in Qinghai-Tibet Plateau

The occurrence, distribution, and ecological risks of psychoactive substances (PSs) in Qinghai-Tibet Plateau (QTP) was investigated in this study. The surface water samples were collected in July in 2020 from five major water bodies, and 9 PSs were determined by liquid chromatography-mass spectrometry. The mean concentrations of the total PSs were 2.19–96.86 ng/L in lakes and 4.56–34.47 ng/L in rivers. Amphetamine (AMP) was the predominant contaminant both in lakes and rivers with a mean concentration of 12.21 ± 22.76 ng/L and 9.83 ± 6.14 ng/L, respectively. The compositions of PSs in lakes and rivers were significantly different. AMP, methadone (MTD), 3,4-methylenedioxyamphetamine (MDA), and ketamine (KET) were the most detected contaminants in lakes, while in rivers AMP, MDA, heroin (HER), and methamphetamine (METH) were the most detected ones. Concentrations of AMP and MTD, the two predominant drugs, varied spatially, with the decreasing concentration of AMP in the order of Huangshui River > Yamzhog Yumco Lake > Qinghai Lake > Lhasa River > Namco Lake, and of MTD in the order of Qinghai Lake > Namco Lake > Huangshui River > Yamzhog Yumco Lake. The risk quotients (RQs) of PSs ranged from 4.44 × 10−6 to 4.32 × 10−2, indicating a low risk of PSs in the aquatic ecosystem in QTP. Compared with other research in the world, the contamination of psychoactive substances in the Qinghai-Tibet Plateau was at relatively low levels with low ecological risks.

Amphetamine or skin cream? The impact of the sampling site on the concentration of controlled substances: a case report

This case report demonstrates the impact of different sampling sites on the quantification of narcotic substances. In 2020, officers secured a syringe containing a light-yellow paste-like substance, for which a drug pre-test indicated a positive result for amphetamine, inducing subsequent analyses of the sample by means of a gaschromatographic-mass spectrometric method (GC–MS) and liquid chromatography–(tandem) mass spectrometry (LC–MS/MS). Depending on the sample location, different results were obtained, with amphetamine not being detected in each sample. Amphetamine was particularly found at the outlet of the syringe, while amphetamine detection on the inside of the syringe at the plunger seal was only possible occasionally and, moreover, in lower concentrations. Based on this and with regard to the comparatively small amphetamine concentrations, contamination of the syringe (especially on the tip of the syringe) was assumed. Hence, the results strengthened the importance of the implication of different sampling sites, when either homogenization of the sample is not feasible or is not performed for reasons of plausibility checks concerning possible contamination of the sample.

Concentrations of psychoactive substances in blood samples from non-fatal and fatal opioid overdoses.

AimThe primary aim was to compare concentrations of psychoactive substances in blood in non‐fatal and fatal opioid overdoses. The secondary aim was to assess the concentration levels of naloxone in blood in non‐fatal overdoses and the association between naloxone findings and concomitantly detected drugs.Method DesignCase‐control study.SettingNorway. Fatal overdoses from 2017 and non‐fatal overdoses from February 2018 to September 2019.CasesThirty‐one non‐fatal and 160 fatal opioid overdose cases. Data from the non‐fatal overdoses were collected from hospital records and blood samples, and data from the fatal overdoses were collected from autopsy reports. Concentrations of psychoactive substances (including ethanol) in blood samples were collected at the time of hospital admission for the non‐fatal overdoses and during autopsy for the fatal overdoses.ResultsThe median number of different substances detected was four for fatal and five for non‐fatal overdoses. The fatal overdoses had higher pooled concentrations of opioids (188 vs 57.2 ng/mL, P < .001), benzodiazepines (5467 vs 2051 ng/mL, P = .005) and amphetamines (581 vs 121 ng/mL, P < .001) than the non‐fatal overdoses. A linear relationship between naloxone and concomitant pooled opioid concentrations was found (95% confidence interval = 0.002‐0.135, P < .05).ConclusionThe total load of drug concentrations was associated with the fatal outcome of an overdose, while the number of drugs used, to a lesser extent, differentiated between those who survived and those who died from an overdose. Higher opioid concentrations were associated with treatment with higher naloxone doses.

Post-Mortem Quantitation of Amphetamine in Cadaveric Fluids in Saudi Arabia

Amphetamine abuse is a known problem in Saudi Arabia; it is estimated that 40% of drug abusers misuse amphetamines. Here, our aim was to perform an up-to-date epidemiological study of amphetamine-related postmortem cases in Jeddah, Saudi Arabia, in which 235 postmortem cases were included. The largest number of cases was recorded for the groups aged between 31 and 40 years (86 cases) and the lowest number of cases was recorded for the group aged between 61 and 70 years old (5 cases). Amphetamine was co-ingested with other drug(s) in 55% of the total cases (blood with sodium fluoride (BN), median, 0.3 mg/L). Approximately 23% of all deaths were due to other co-ingested drugs (BN, median, 0.2 mg/L). Amphetamines alone were detected in 107 cases, (BN, median, 0.5 mg/L). Amphetamine was the sole cause of death in 16% of the studied cases (BN, median, 1.0 mg/L). The combination of amphetamine and a pre-existing disease were observed in 9.4% of all deaths (BN, median, 0.7 mg/L). The causes of death were determined to be accidental in the majority (47%) of cases, homicides in 26% of cases, suicides in 11% of cases, and unknown in 7% of cases. This is the first discussion of the amphetamine concentration in bile in amphetamine-related deaths, the relationship between amphetamine concentration in different bodily fluids, and the amphetamine concentration in putrefied corpses. This study concluded that amphetamine abuse in Jeddah, Saudi Arabia, increased over 400% between 2012 and 2018, and 41% of these cases involved violence. This result also suggests that preventive programs targeting youth and adolescent students are required to keep schools and universities free from drugs, especially amphetamines.

Recreational Drug Use During the Amsterdam Dance Event: Impact on Emergency Services.

Background:Recreational drug use is common at large-scale dance events such as the Amsterdam Dance Event (ADE) and severe drug-related complications and deaths occur. Increasing concentrations of cocaine, amphetamine and MDMA have been observed in samples from dance events. Therefore, large dance events are expected to cause an increasing amount of recreational drug related complaints (RDRC) and an increased demand on emergency medical services.Aim:To evaluate the impact of recreational drug related complaints (RDRC) during ADE 2016, compared to regular weeks, and to evaluate the requirement for additional medical personnel.Methods:For this prospective, observational cohort study, patients >12 years old presenting with RDRC at first aid stations (FAS), ambulance service (AA) and ED during ADE, between October 19th and October 24th 2016 were included. From 2 EDs and AA, the RDRC 2 weeks before and after ADE were also collected.Results:An estimated 375.000 people attended ADE. The number of patients with RDRC was 459 at the FAS, 113 at AA and 81 at the ED, and increased significantly during ADE with 225% at AA and with 236% at OLVG ED. Eight patients were admitted. A higher percentage of poly-drug use among ED patients (58%) was found, compared to FAS patients (25%). Also, the proportion of tourists in ED’s (51%) was higher compared to FAS (30%).Conclusions:During ADE 2016, the number of intoxicated patients increased significantly. Eight patients were admitted to the hospital, without any deaths. The absolute number of patients stayed within normal range of emergency medical services capacity.

Development of best practices in physiologically based pharmacokinetic modeling to support clinical pharmacology regulatory decision-making-A workshop summary.

Development of best practices in physiologically based pharmacokinetic modeling to support clinical pharmacology regulatory decision-making-A workshop summary.

Enantioselective Quantification of Amphetamine and Metabolites in Serum Samples: Forensic Evaluation and Estimation of Consumption Time.

In forensic toxicology, amphetamine intoxications represent one of the most common case groups and present difficult questions for toxicologists. Estimating the time of consumption and the current influence of the stimulant is particularly difficult when only total amphetamine concentrations are considered. Stereoselective analysis and the consideration of metabolites can provide valuable information to facilitate interpretation. An enantioselective liquid chromatography−tandem mass spectrometry (LC-MS/MS) method for detection of amphetamine, norephedrine and 4-hydroxyamphetamine was developed. Validation showed satisfactory selectivity, sensitivity, linearity (0.5–250 ng/mL), precision and accuracy for all enantiomers. The method was applied to a collective of 425 forensic serum samples and 30 serum samples from psychiatric inpatients stating their last time of amphetamine consumption. Norephedrine and 4-hydroxyamphetamine were detected more frequently at higher amphetamine concentrations and at lower amphetamine (R)/(S) concentration ratios, possibly indicating recent consumption. Mean (R)/(S) ratio of amphetamine was 1.14, whereas higher ratios (mean 1.36) were found for amphetamine concentrations below 100 ng/mL. The (R)/(S) ratios of psychiatric inpatients significantly correlated with the reported time intervals to last consumption. The use of amphetamine (R)/(S) ratios and the simultaneous detection of metabolites are promising factors that can facilitate estimation of consumption time and current impairment.