Identification Of Amphetamine Research Articles

Identification of amphetamine as a stimulant drug by pristine and doped C70 fullerenes: a DFT/TDDFT investigation.

The density functional theory (DFT) was used to examine the electronic reactivity and sensitivity of a pristine, Si, and Al-doped fullerene C70 with AM drug. AM drug has been shown to be physically absorbed by its N-head on the pristine C70 with an adsorption energy of about - 1.09kcal/mol and to have no impact on the electric conductivity of that cluster. The atom substitution of Si and Al for C atoms at C70 significantly increases C70 fullerene reactivity, with adsorption energy predictions of approximately - 31.09 and - 45.59kcal/mol, respectively. The energy difference of LUMO and HOMO, i.e., Eg from C70 fullerene, significantly affects AM drug. Significant LUMO destabilization in Al-C70 by adsorption of the drug AM boosts the electrical conductivity of Al-C70 while generating electric signals that are related to the environmental presence of AM drug. Hence, Al-doped C70 is demonstrated to be an effective electronic AM drug sensor. In contrast to Si-C70 fullerene, significant AM-drug adsorption effects on Fermi and Si-C70 work functions make Si-C70 an Ф-type candidate for AM drug sensor applications. The time-dependent theory of the functional density shows that the AM/Al-C70 complex is steadily situated at a maximum peak of 784.15nm.

Paramethoxymethamphetamine (Mitsubishi turbo) abuse: Case report and literature review

IntroductionParamethoxymethamphetamine and paramethoxyamphetamine (PMMA and PMA) are two so-called designer amphetamines, which appear from time to time on the illegal narcotics market in many countries. They are frequently sold as ecstasy or amphetamine, often mixed with amphetamine or methamphetamine [1, 2]. Paramethoxyamphetamine (PMA) is a hallucinogenic synthetic substituted amphetamine with capable of development of dependence [3]. The purpose of this report is to review the clinical evidence for the potential of abuse of paramethoxyamphetamine. We propouse a case report and literature review.MethodWe conducted a systematic review of the literature with the principal database (PubMed, Enbase, PsychInfo) and we present a case report.ResultsThe effects of paramethoxyamphetamine is characterized at the beginning with symptoms like euphoria, derealizzation, psychomotor activation, feeling in tune with surroundings and in love for friends, who come to visual and auditory illusions and hallucinations, paranoid delusion, and violent agitation.Discussion and conclusionThe use of these recreational drugs is especially common among young people participating in rave parties. Occasionally paramethoxymethamphetamine (PMMA) or paramethoxyamphetamine (PMA) are found in street drugs offered as ecstasy. Further research is warranted to replicate our clinical and qualitative observations and, in general, quantitative studies in large samples followed up over time are needed. Methodological limitations, clinical implications and suggestions for future research directions are considered.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Simultaneous determination of 40 novel psychoactive stimulants in urine by liquid chromatography–high resolution mass spectrometry and library matching

The emergence of novel psychoactive substances is an ongoing challenge for analytical toxicologists. Different analogs are continuously introduced in the market to circumvent legislation and to enhance their pharmacological activity. Although detection of drugs in blood indicates recent exposure and link intoxication to the causative agent, urine is still the most preferred testing matrix in clinical and forensic settings. We developed a method for the simultaneous quantification of 8 piperazines, 4 designer amphetamines and 28 synthetic cathinones and 4 metabolites, in urine by liquid chromatography coupled to high-resolution mass spectrometry (LC–HRMS). Data were acquired in full scan and data dependent MS2 mode. Compounds were quantified by precursor ion exact mass, and confirmed by product ion spectra library matching, taking into account product ions’ exact mass and intensities. One-hundred μL urine was subjected to solid phase cation exchange extraction (SOLA SCX). The chromatographic reverse-phase separation was achieved with gradient mobile phase of 0.1% formic acid in water and in acetonitrile in 20min. The assay was linear from 2.5 or 5 to 500μg/L. Imprecision (n=15) was <15.4%, and accuracy (n=15) 84.2–118.5%. Extraction efficiency was 51.2–111.2%, process efficiency 57.7–104.9% and matrix effect ranged from −41.9% to 238.5% (CV<23.3%, except MDBZP CV<34%). Authentic urine specimens (n=62) were analyzed with the method that provides a comprehensive confirmation for 40 new stimulant drugs with specificity and sensitivity.

Predictors of positive drug screens after deployment to Iraq or Afghanistan in the military drug testing program

s / Drug and Alcohol Dependence 146 (2015) e118–e201 e169 Methods: Urinalysis tests for cocaine, heroin, THC, amphetamines, and/or designer amphetamines, routinely tested by the DoD, were examined to estimate the percent of the sample with any positive drug test 6-month to 3-year postdeployment (follow up). Demographic and deployment characteristics were examined as potential predictors of a positive drug screen. Multivariate models controlled for study design variables (number of tests, last collection date relative to deployment end). Results: Of AD enlisted members, >80% with urinalysis data were analyzed. Most had at least one random test (median 4) during followup. An estimated 2.74%, 95% confidence interval CI: 2.68–2.89% tested positive. Controlling for design, demographics, and deployment characteristics, with increased odds of a positive drug screen were combat specialist occupation (relative to 4 other groups), in early cohort (deployment began before FY2011), short deployment (relative to 1 year, or >1 year), first deployment (prior deployment ended >365 days before index), and assigned to aWarrior TransitionUnit (WTU, rather than regularmilitary duties) upon return. Conclusions: Preliminary findings suggest that combat specialist occupations andfirst deployersweremost at risk. Twomeasures which may be proxies for returning wounded also had increased odds of a positive drug test. Knowledge of these characteristics may help target new strategies or interventions such as additional screening or brief counseling. Financial Support: NIDA R01DA030150. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.375 Gender differences in risk factors for nonmedical use of prescription stimulants among youth 10 to 18 years in the US Sonam O. Lasopa, Linda Cottler, Krishna Vaddiparti, Catherine W. Striley University of Florida, Gainesville, FL, United States Aims: Nonmedical use of prescription stimulants (NMU) is a significant public health concern with increased risk among adolescent girls. Given the complex and multiple pathways that contribute to drug use, this study examines gender differences and gender specific associations of NMU across domains. Methods: Data comes from the National Monitoring of Prescription Stimulants Study (NMAPSS) which surveyed 11,048 10 to 18 year olds via an entertainment venue intercept recruitment method. NMU was defined as using prescription stimulants more than prescribed, stimulants that belonged to someone else, by non-oral routes, or use to get high. Photos of pills were used to ensure proper recall. Variables examined included those in the socio-demographic, psychological and peer domains. Results: Among the 3.6% of youth reporting past 30 day NMU, 46% were girls. Among youth with NMU, depression (54% vs. 46%), anxiety (57% vs. 43%) and weight concerns (72% vs. 28%) were significantly higher in girls than boys, though boys had higher rates of ADHD (62% vs. 38%) and conduct problems (66% vs. 34%). Multivariable logistic regression indicated that girls with ADHD (OR 1.65), weight concerns (OR 3.38), and thosewho smoked (OR 2.48), or reported illegal drug use (OR 4.87) or had a friend who used stimulants (OR 6.53) weremore likely than thosewithout to report NMU. Among boys, increased odds of NMU were found for alcohol use (OR 2.24), illegal drugs (OR 3.25) or having a friend who used stimulants (OR 6.61). Conclusions: General and specific risk factors based on gender are associated with NMU across demographic, psychological and peer domains. The implications of gender differences in vulnerability to NMU pertain to the design of targeted prevention and interventions programs. Financial Support: Fogarty International Centre Indo-US Training Program in Non-Communicable Diseases (Grant No D 43TW009120; Sonam O Lasopa, Fellow; PI: Cottler). NMAPSS was conducted under contract from Pinney Associates, Inc. Pinney is provided funding by Shire Pharmaceutical and Noven Pharmaceuticals. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.376 Impaired executive function, drug and sex risk, and HIV infection in African-American men W.W. Latimer1, Maria R. Khan2, Joy D. Scheidell 2, Eugene M. Dunne1 1 Clinical and Health Psychology, University of Florida, Gainesville, FL, United States 2 Epidemiology, University of Florida, Gainesville, FL,

Determination of Amphetamine and Methylphenidate in Exhaled Breath of Patients Undergoing Attention-Deficit/Hyperactivity Disorder Treatment

It has been discovered recently that exogenous substances are detectable in exhaled breath after intake. Exhaled breath therefore constitutes a new possible matrix in clinical pharmacology and toxicology. The present work was aimed at exploring this possibility further by a study on patients treated for attention-deficit/hyperactivity disorder with D-amphetamine and methylphenidate. Thirteen patients (age range: 32-61 years; 5 women) were included in the study, and breath and urine samples were collected at different times in the dose interval. Analyses of breath and urine samples were done with liquid chromatography-mass spectrometry methods. Urine was examined for amphetamine, methylphenidate, and its metabolite ritalinic acid. Among the 9 patients who received D-amphetamine medication in daily doses of 20-100 mg, amphetamine was detected in all subjects in amounts ranging from 1200 to 30,800 picogram per filter. Among 8 patients receiving methylphenidate medication in daily doses of 80-400 mg, it was detected and quantified in 7 of the cases in amounts ranging from 150 to 10,400 picogram per filter and ritalinic acid was detected and quantified in 3 of the cases ranging from 35 to 360 picogram per filter. In 1 case, methylphenidate was only detectable in breath and urine, whereas ritalinic acid was quantifiable in urine, which could indicate noncompliance, with the 4 hours of dose regimen prescribed. In a number of cases, the sampling was performed 24 hours after the last dose intake. Identification of amphetamine and methylphenidate was based on correct chromatographic retention time and correct product ion ratio with detection performed in selected reaction monitoring mode. The results confirm that amphetamine is present in exhaled breath after intake and demonstrate for the first time the presence of methylphenidate and ritalinic acid after its intake. This gives further support to the potential use of exhaled breath for detecting drug intake.

Evaluation of Designer Amphetamine Interference in GC–MS Amine Confirmation Procedures

In recent years, a class of new designer drugs commonly referred to as 'bath salts' have made their way to the illicit drug market. The most common drugs encountered are designer amphetamines and cathinones. Many analytical methods for analysis and identification of bath salts have been published, but there has been little reported on their impact on existing gas chromatography-mass spectrometry (GC-MS) amine confirmation methods. Due to structural similarities, the potential exists that designer amphetamines may interfere with methods used for analysis of sympathomimetic amines. Methiopropamine, 4-fluoroamphetamine, 4-fluoromethamphetamine (4-FMA) and 4-methylamphetamine were examined for potential interference with immunoassays and GC-MS confirmation analysis utilizing three derivatization procedures: R(-)-α-methoxy-α-trifluoromethylphenylacetyl chloride (R-MTPAC), heptafluorobutyric anhydride (HFBA) and chlorodifluoroacetic anhydride (ClF(2)AA). Significant cross-reactivity was observed with all the four compounds on the Syva Emit(®) II Plus Amphetamines and Roche KIMS Amphetamines II immunoassays. Laboratories utilizing GC-MS selected-ion-monitoring confirmation methods with R-MTPAC, HFBA or ClF(2)AA derivatives could experience potential chromatographic and mass spectral interferences from 4-fluroamphetamine, 4-FMA and methiopropamine in the form of ion ratio and quantitative failures. Careful ion selection, proper selectivity and specificity studies during method validation and rigid chromatographic and spectral acceptance criteria are required to assure the robustness and accuracy of GC-MS methods.

The Toxicology Investigators Consortium Case Registry—The 2012 Experience

In 2010, the American College of Medical Toxicology (ACMT) established its Case Registry, the Toxicology Investigators Consortium (ToxIC). All cases are entered prospectively and include only suspected and confirmed toxic exposures cared for at the bedside by board-certified or board-eligible medical toxicologists at its participating sites. The primary aims of establishing this Registry include the development of a realtime toxico-surveillance system in order to identify and describe current or evolving trends in poisoning and to develop a research tool in toxicology. ToxIC allows for extraction of data from medical records from multiple sites across a national and international network. All cases seen by medical toxicologists at participating institutions were entered into the database. Information characterizing patients entered in 2012 was tabulated and data from the previous years including 2010 and 2011 were included so that cumulative numbers and trends could be described as well. The current report includes data through December 31st, 2012. During 2012, 38 sites with 68 specific institutions contributed a total of 7,269 cases to the Registry. The total number of cases entered into the Registry at the end of 2012 was 17,681. Emergency departments remained the most common source of consultation in 2012, accounting for 61% of cases. The most common reason for consultation was for pharmaceutical overdose, which occurred in 52% of patients including intentional (41%) and unintentional (11%) exposures. The most common classes of agents were sedative-hypnotics (1,422 entries in 13% of cases) non-opioid analgesics (1,295 entries in 12% of cases), opioids (1,086 entries in 10% of cases) and antidepressants (1,039 entries in 10% of cases). N-acetylcysteine (NAC) was the most common antidote administered in 2012, as it was in previous years, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab fragments were administered in 109 cases or 82% of cases in which a snake envenomation occurred. There were 57 deaths reported in the Registry in 2012. The most common associated agent alone or in combination was the non-opioid analgesic acetaminophen, being reported in 10 different cases. Other common agents and agent classes involved in death cases included ethanol, opioids, the anti-diabetic agent metformin, sedatives-hypnotics and cardiovascular agents, in particular amlodipine. There were significant trends identified during 2012. Abuse of over-the-counter medications such as dextromethorphan remains prevalent. Cases involving dextromethorphan continued to be reported at frequencies higher than other commonly abused drugs including many stimulants, phencyclidine, synthetic cannabinoids and designer amphetamines such as bath salts. And, while cases involving synthetic cannabinoids and psychoactive bath salts remained relatively constant from 2011 to 2012 several designer amphetamines and novel psychoactive substances were first reported in the Registry in 2012 including the NBOME compounds or "N-bomb" agents. LSD cases also spiked dramatically in 2012 with an 18-fold increase from 2011 although many of these cases are thought to be ultra-potent designer amphetamines misrepresented as "synthetic" LSD. The 2012 Registry included over 400 Adverse Drug Reactions (ADRs) involving 4% of all Registry cases with 106 agents causing at least 2 ADRs. Additional data including supportive cares, decontamination, and chelating agent use are also included in the 2012 annual report. The Registry remains a valuable toxico-surveillance and research tool. The ToxIC Registry is a unique tool for identifying and characterizing confirmed cases of significant or potential toxicity or complexity to require bedside care by a medical toxicologist.

Characterization of synthetic routes to ‘Bromo‐DragonFLY’ and benzodifuranyl isopropylamine homologues utilizing ketone intermediates. Part 1: Synthesis of ketone precursors

Bromo-DragonFLY (BDF) and many of its analogues are misused as recreational drugs due to their potency as psychoactive substances. To date, none of the published routes to these designer amphetamines have exploited a ketone intermediate. It is well known that benzyl methyl ketone (BMK) can be employed as a precursor in the synthesis of amphetamine. Similarly, it is reasonable to assume that ketone precursors may potentially be utilized in the clandestine synthesis of BDF and its homologues. This paper describes the multifaceted synthesis of novel precursor ketones structurally related to BDF, namely benzodifuranyl propanone 16, its tetrahydrobenzodifuranyl homologue 8, and their brominated analogues 12 and 20. Their characterization by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy ((1) H-NMR), carbon nuclear magnetic resonance spectroscopy ((13) C-NMR), high performance liquid chromatography (HPLC), gas chromatography (GC) and mass spectrometry (MS) is also described.

Comparison of LUCIO®‐direct ELISA with CEDIA immunoassay for ‘zero tolerance’ drug screening in urine as required by the German re‐licensing guidelines

The performance of the previously validated LUCIO(®)-Direct-enzyme linked immunosorbent assay (direct ELISA) screening tests according to forensic guidelines is compared to that of cloned enzyme donor immunoassays (CEDIA) test for drugs of abuse in urine as defined in the new re-licensing German medical and psychological assessment (MPA) guidelines. The MPA screening cut-offs correspond to 10 ng/ml 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), 50 ng/ml amphetamine and designer amphetamines, 25 ng/ml morphine, codeine and dihydrocodeine, 30 ng/ml benzoylecgonine, 50 ng/ml methadone metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and metabolites of diazepam, oxazepam, bromazepam, alprazolam, flunitrazepam and lorazepam at 50 ng/ml. Average relative sensitivities and relative specificities were 99.7 % and 98.4 % for direct ELISA and 66 % and 91.4 % for CEDIA, respectively.

Forgiftning med parametoksymetamfetamin

Since the summer of 2010, there has been an epidemic of deaths related to paramethoxymethamphetamine (PMMA) in Norway. We present a review of the pharmacology and toxicology of the substance. The review is based on a literature search in the databases PubMed, Ovid and MEDLINE. A discretionary selection was made of relevant articles. Paramethoxymethamphetamine and paramethoxyamphetamine (PMA) are two so-called designer amphetamines which appear from time to time on the illegal narcotics market in many countries. They are frequently sold as ecstasy or amphetamine, often mixed with amphetamine or methamphetamine. The substances, known on the street as «Death», have potent serotonergic effects and are associated with significant toxicity. Many deaths have been reported worldwide, even after intake of an «ordinary user dose». The narcotic effect is not very pronounced and the onset is slow, which may lead to unintentional overdosing. In cases of severe intoxation that are apparently related to intake of amphetamine or ecstasy, PMMA/PMA intoxation should be suspected.

Development and validation of two LC-MS/MS methods for the detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine using turbulent flow chromatography

In the context of driving ability diagnostics in Germany, administrative cutoffs for various drugs and pharmaceuticals in urine have been established. Two liquid chromatography-tandem mass spectrometry methods for simultaneous detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine were developed and validated. A 500-μL aliquot of urine was diluted and fortified with an internal standard solution. After enzymatic cleavage, online extraction was performed by an ion-exchange/reversed-phase turbulent flow column. Separation was achieved by using a reversed-phase column and gradient elution. For detection, a Thermo Fisher TSQ Quantum Ultra Accurate Mass tandem mass spectrometer with positive electrospray ionization was used, and the analytes were measured in multiple-reaction monitoring mode detecting two transitions per precursor ion. The total run time for both methods was about 15 min. Validation was performed according to the guidelines of the Society of Toxicological and Forensic Chemistry. The results of matrix effect determination were between 78% and 116%. The limits of detection and quantification for all drugs, except zopiclone, were less than 10 ng/mL and less than 25 ng/mL, respectively. Calibration curves ranged from 25 to 200 ng/mL for amphetamines, designer amphetamines, and benzoylecgonine, from 25 to 250 ng/mL for benzodiazepines, from 12.5 to 100 ng/mL for morphine, codeine, and dihydrocodeine, and from 5 to 50 ng/mL for buprenorphine and norbuprenorphine. Intraday and interday precision values were lower than 15%, and bias values within ± 15% were achieved. Turbulent flow chromatography needs no laborious sample preparation, so the workup is less time-consuming compared with gas chromatography-mass spectrometry methods. The methods are suitable for quantification of multiple analytes at the cutoff concentrations required for driving ability diagnostics in Germany.

Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats

BackgroundReports from US, UK and European drug policy entities, and ongoing media accounts, show increasing recreational use of 4-methylmethcathinone (4-MMC, mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV). Severe sympathomimetic symptoms, hallucinations, psychoses, and even deaths have been reported, yet little scientific information is available on the effects of these compounds in laboratory models. Available studies on the neurochemistry of these drugs show that 4-MMC and MDPV enhance DA neurotransmission, while 4-MMC additionally enhances 5-HT neurotransmission – a pattern much like that reported for methamphetamine versus 3,4-methylenedioxymethamphetamine (MDMA). As is the case for designer amphetamines, these neurochemical distinctions may predict differential potential for repetitive versus episodic abuse and distinct lasting toxicities. MethodsThis study determined relative locomotor stimulant effects of 4-MMC (1–10mg/kg, s.c.) and MDPV (0.5–5.6mg/kg, s.c.), in comparison with d-methamphetamine (MA; 0.5–5.6mg/kg, s.c.) and MDMA (1–7.5mg/kg, s.c.) on a measure of locomotor activity – voluntary wheel running – in male Wistar rats (N=8). ResultsCompared to counts of wheel rotations after saline, a biphasic change in the pattern of counts was observed after injections of MA and MDPV, with relatively higher counts following lower doses and lower counts following the highest dose. However, monophasic, dose-dependent reductions in counts were observed in response to injections of MDMA and 4-MMC. ConclusionThus, voluntary wheel running yielded the same categorical distinctions for these drugs as did prior experiments testing the effects of these drugs on monoaminergic neurotransmission. These data indicate that MDPV produces prototypical locomotor stimulant effects whereas 4-MMC is more similar to the entactogen MDMA.

Acute effects of d‐methamphetamine, 3,4‐methylenedioxypyrovalerone, 3,4‐methylenedioxymethamphetamine, and 4‐methylmethcathinone on wheel activity in rats

A recent DEA report and ongoing media accounts show increasing recreational use of 4‐methylmethcathinone (4‐MMC, mephedrone) and 3,4‐methylenedioxypyrovalerone (MDPV). Some severe sympathomimetic symptoms, hallucinations, psychoses, and even deaths have been reported. Recent studies showed that 4‐MMC and MDPV enhanced DA neurotransmission, while 4‐MMC also increased 5‐HT neurotransmission, much like 3,4‐methylenedioxymethamphetamine (MDMA). Therefore these novel cathinone recreational drugs may predict differential abuse potential and toxicities, as is the case for designer amphetamines. This study determined relative locomotor stimulant effects of 4‐MMC and MDPV, in comparison with d‐methamphetamine (METH) and MDMA, in male Wistar rats provided an activity wheel. Results showed a biphasic pattern for METH and MDPV, with increased wheel activity following lower doses and inhibition of activity at the highest dose. Monophasic, dose‐dependent reductions in activity were produced by MDMA and 4‐MMC. The data suggests MDPV produces typical locomotor stimulant effects whereas 4‐MMC is more similar to the entactogen MDMA. USPHS grants: DA024105 and DA024705.

Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenylalkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenylalkylamine designer drugs, such as 3,4‐methylenedioxymethamphetamine (MDMA), 3,4‐methylenedioxyethylamphetamine (MDEA), N‐methyl‐1‐(3,4‐methylenedioxyphenyl)‐2‐butanamine (MBDB), 3,4‐methylenedioxyamphetamine (MDA), and 3,4‐(methylenedioxyphenyl)‐2‐butanamine (BDB), are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA) anhydride and analyzed by gas chromatography/mass spectrometry using electron ionization in positive mode. Gas chromatographic separation for TFA derivatives of all compounds was successfully resolved using an Equity‐5 fused silica capillary column with a poly (5% diphenyl‐95% dimethylsiloxane) stationary phase. Base peaks or prominent peaks of MA, AM, MDMA, MDEA, MBDB, MDA, and BDB appeared at m/z 154, 140, 154, 168, 168, 135, and 135, respectively. These occurred due to α‐cleavage from the amide nitrogen, splitting into the TFA imine species and benzyl or methylenedioxybenzyl cations. Further prominent fragment ions at m/z 118 for MA and AM, m/z 162 for MDMA, MDEA, and MDA, and m/z 176 for MBDB and BDB were produced by cleavage of the phenylpropane or methylenedioxypropane hydrocarbon radical cation via a hydrogen rearrangement. These fragmentation pathways for the TFA derivatives of all the compounds are summarized and illustrated in this paper.

LC-MS/MS screening method for designer amphetamines, tryptamines, and piperazines in serum

Since the late 1990s and early 2000s, derivatives of well-known designer drugs as well as new psychoactive compounds have been sold on the illicit drug market and have led to intoxications and fatalities. The LC-MS/MS screening method presented covers 31 new designer drugs as well as cathinone, methcathinone, phencyclidine, and ketamine which were included to complete the screening spectrum. All but the last two are modified molecular structures of amphetamine, tryptamine, or piperazine. Among the amphetamine derivatives are cathinone, methcathinone, 3,4-DMA, 2,5-DMA, DOB, DOET, DOM, ethylamphetamine, MDDMA, 4-MTA, PMA, PMMA, 3,4,5-TMA, TMA-6 and members of the 2C group: 2C-B, 2C-D, 2C-H, 2C-I, 2C-P, 2C-T-2, 2C-T-4, and 2C-T-7. AMT, DPT, DiPT, MiPT, DMT, and 5MeO-DMT are contained in the tryptamine group, BZP, MDBP, TFMPP, mCPP, and MeOPP in the piperazine group. Using an Applied Biosystems LC-MS/MS API 365 TurboIonSpray it is possible to identify all 35 substances. After addition of internal standards and mixed-mode solid-phase extraction the analytes are separated using a Synergi Polar RP column and gradient elution with 1 mM ammonium formate and methanol/0.1% formic acid as mobile phases A and B. Data acquisition is performed in MRM mode with positive electro spray ionization. The assay is selective for all tested substances. Limits of detection were determined by analyzing S/N-ratios and are between 1.0 and 5.0 ng/mL. Matrix effects lie between 65% and 118%, extraction efficiencies range from 72% to 90%.

Isolation and identification of amphetamines in urine by thin-layer chromatography

Amphetamine derivatives are psychostimulating drugs. They are characterized by their strong central stimulating, anorectic, and peripheral sympathomimetic effect. They are used in the therapy of narcolepsy; amphetamine derivatives are relatively successful and, because administration is for a short time only, the effects of intolerance do not appear, in contrast with their use in the treatment of anorexia. Amphetamine derivatives incite a state of increased wakefulness, avert sleep, and accelerate psychomotor activity; the brain is able to capture and process a greater number of stimuli. This effect is, however, achieved at the cost of the quality of brain function. Alerting amines are abused for their euphoric effects by addicts. Amphetamine (AP) is a typical representative of the psychostimulants. It is well adsorbed from the gastrointestinal tract and easily penetrates the blood–brain barrier. The biological half-life is 12–34 h, depending on the pH of urine. Many individuals orally abuse amphetamine for abolition of fatigue, enhancement of wakefulness, and mood elevation. It appears in urine 20 min after administration and chronic consumers can have urine levels in the range

Chiral separation and quantification of R/S-amphetamine, R/S-methamphetamine, R/S-MDA, R/S-MDMA, and R/S-MDEA in whole blood by GC-EI-MS

The enantioselective composition of the amphetamines is of interest, as the enantiomers show differences in their pharmacological effects and several methods for chiral separation of amphetamines have been described. Only a few methods have used whole blood as matrix and none of these separates both classic amphetamines (amphetamine and methamphetamine) and designer amphetamines (MDA, MDMA and MDEA). The aim of this study was, therefore, to develop a method for enantioselective analysis of AM, MA, MDA, MDMA, and MDEA in whole blood. The amphetamines were extracted from 0.5 g of whole blood by liquid-liquid extraction. After derivatization with R-MTPCl, the resulting diastereomers were separated by GC on a HP-5MS column and detected by SIM-MS. R-MTPCl was used as derivatization reagent because of the stability of this reagent and good separation of these analytes. Through the method, development time and temperature of the derivatization were optimized, and by admixture of 0.02% triethylamine it became possible to detect the amphetamines in adequately low concentrations as more analytes were derivatized. The method was validated and it was linear from 0.004 to 3 microg/g per enantiomer. The accuracy was within 91-115%, while the repeatability and reproducibility were < or =15% R.S.D. A method suitable for enantioselective separation and analysis of the amphetamines has been achieved, and the method was applied to analysis of whole blood samples originating from traffic and criminal cases and post mortem cases.

The Identification of a Chlorinated MDMA

The abuse of the designer amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA) is increasing throughout the world. They have become popular drugs at all night techno dance parties, and their detection is an important issue. The objective of the presented study was to identify an unknown compound detected by thin-layer chromatography (TLC) in the urine of an illicit drug abuser. The compound was isolated by TLC and analyzed by gas chromatography-mass spectrometry (GC-MS) in electron ionization (EI) and positive ion chemical ionization (PICI) mode to elucidate its chemical structure. Based on EI-MS and PICI-MS mass spectral data, the unknown compound was indicated to be a structure similar to MDMA, substituted by a single chlorine atom-a chlorinated MDMA (Cl-MDMA). To confirm the Cl-MDMA structure, the unknown compound was silylated, trifluoroacetylated, acetylated, heptafluorobutyrylated, and analyzed by GC-MS. The position of the chlorine atom cannot be assigned exactly from the mass spectral data presented here; however, we believe that the unknown compound could be 6-Cl-MDMA.

Review: Pharmacokinetics of illicit drugs in oral fluid

This article reviews studies that have measured drug concentrations in oral fluid following controlled dosing regimens. A total of 23 studies have been identified over the last 15 years. These show that the amphetamines including designer amphetamines, cocaine, cannabis and cocaine are quickly found in oral fluid following dosing and usually have similar time-courses to that in plasma. Following common doses peak oral fluid concentrations exceed 0.1 μg/mL and often even 1 μg/mL. The drug concentration will depend on whether a dilution step occurs with buffer as part of the sampling procedure. The uses of collectors that stimulate oral fluid usually reduce the drug concentration compared to a non-stimulated manner. This reduction will not disadvantage the recipient since it will potentially reduce the detectablity of drug in oral fluid compared to non-stimulated collections. Only one recent study has been reported for a benzodiazepine. This showed nanogram per milliliter concentrations for flunitrazepam. More studies are required for benzodiazepines and indeed for other drugs, particularly in multiple drug situations and where disease may affect the pharmacokinetics of drugs.

A rapid and sensitive liquid chromatography-tandem mass spectrometry method for the determination of amphetamine and related designer drugs in urine

Une methode pour l'analyse directe de six amphetaminiques dans les urines a ete developpee en utilisant la chromatographie liquide couplee a la spectrometrie de masse en tandem (LC-MS/MS). Nous avons ajoute 90 μl d'un melange d'etalons internes (1 pg/mL de d 5 -AMP, de d 5 -MET, de d 5 -MDA, de d 5 -MDMA, de d 5 -MDEA et de d 5 -MBDB) a 10 μl d'urine, melange par vortex et centrifuge. Les echantillons ont ete analyses par LC-MS/MS en mode MRM apres separation sur une colonne C18 a phase inverse en utilisant un gradient d'elution. La separation et la detection de tous les composes ont ete accomplies en huit minutes. La linearite a ete etablie pour tous les composes, de 78 a 100000 ng/mL. Les coefficients de correlation etaient superieurs a 0.998. Les limites de quantification etaient inferieures a 10 ng/mL, sauf pour l'amphetamine et la MDA (78 ng/mL). La repetabilite (CV%) et la reproductibilite variaient respectivement entre 2.62 et 16.26% et entre 0.86 et 11.98%. En ce qui concerne l'exactitude, le pourcentage de biais a 78 et 10000 ng/mL variait entre 0.16 et 7.17 %. La surface des pics des amphetamines ajoutees a de l'urine variait entre 85 et 100% de celle des amphetamines dissous dans un melange d'eau et de methanol, excepte pour l'amphetamine et le MDA. Le carry-over etait negligeable et la stabilite (156 et 5000 ng/mL) apres stockage a la temperature ambiante pendant 24h etait acceptable. En conclusion, la methode presentee permet la determination exacte, precise et rapide de six amphetaminiques dans les urines sur une plage de concentration large.