Analysis of Stimulants in Sweat and Urine Using Disposable Pipette Extraction and Gas Chromatography Coupled to Mass Spectrometry in the Context of Doping Control.

Urine is initially collected from athletes to screen for the presence of illicit drugs. Sweat is an alternative sample matrix that provides advantages over urine including reduced opportunity for sample adulteration, longer detection-time window and non-invasive collection. Sweat is suitable for analysis of the parent drug and metabolites. In this study, a method was developed and validated to determine the presence of 13 amphetamine- and cocaine-related substances and their metabolites in sweat and urine using disposable pipette extraction (DPX) by gas chromatography coupled to mass spectrometry. The DPX extraction was performed using 0.1 M HCl and dichloromethane:isopropanol:ammonium hydroxide (78:20:2, v/v/v) followed by derivatization with N-methyl-N-(trimethylsilyl) trifluoroacetamide at 90°C for 20 min. DPX extraction efficiencies ranged between 65.0% and 96.0% in urine and 68.0% and 101.0% in sweat. Method accuracy was from 90.0% to 104.0% in urine and from 89.0% to 105.0% in sweat. Intra-assay precision in urine and in sweat were <15.6% and <17.8%, respectively, and inter-assay precision ranged from 4.70% to 15.3% in urine and from 4.05% to 15.4% in sweat. Calibration curves presented a correlation coefficient -0.99 for all analytes in both matrices. The validated method was applied to urine and sweat samples collected from 40 professional athletes who knowingly took one or more of the target illicit drugs. Thirteen of 40 athletes were positive for at least one drug. All the drugs detected in the urine were also detected in sweat samples indicating that sweat is a viable matrix for screening or confirmatory drug testing.

Análisis médico legal de la toxicomanía por MDMA: reporte de caso / Medical-legal relationship of MDMA drug addiction: case report

Resumen El análisis por toxicomanía representa un proceso común solicitado por la Autoridad Judicial para determinar si un usuario presenta hallazgos compatibles con el uso de una droga a nivel clínico, componentes histológicos, patológicos y toxicológicos que puedan generar su uso. Es necesario destacar las limitaciones del ambiente clínico donde se pueden generar múltiples hallazgos, y de la toxicología forense donde a pesar de la especificidad a la que se asocia; también se encuentra limitada por la capacidad de sus equipos tecnológicos. La resonancia magnética nuclear cuantitativa de hidrógeno representa grandes ventajas al demostrar la presencia de una droga ilegal, así como la posibilidad de disminuir costos y tiempo laboral. El uso del MDMA como tratamiento con una reciente aprobación para un estudio de fase III por la FDA, también requiere que se valore el motivo de su uso, por lo que para realizar un análisis médico legal se contemplaron diversos elementos de juicio a fin de satisfacer la evaluación sobre la toxicomanía por MDMA en un usuario que presentó un tejido granular blanco tipo polvo en la sección distal del tabique nasal y negó el consumo de metanfetaminas.

Abstract The analysis for drug addiction represents a common process requested by the Judicial Authority to determine if a user presents findings compatible with the use of a drug at a clinical level, histological, pathological and toxicological components that may generate its use. It is necessary to highlight the limitations of the clinical environment where multiple findings can be generated, and of forensic toxicology where despite the specificity to which it is associated; it is also limited by the capacity of its technological equipment. Quantitative hydrogen nuclear magnetic resonance represents great advantages when demonstrating the presence of an illegal drug, as well as the possibility of reducing costs and labor time. The use of MDMA as a treatment with a recent approval for a phase III study by the FDA, also requires that the reason for its use be assessed, therefore, in order to carry out a legal medical analysis, various elements of judgment were considered in order to satisfy evaluation of MDMA drug addiction in a user who presented with white powder-like granular tissue in the distal section of the nasal septum and denied the use of methamphetamine.

Dopant for detection of methamphetamine in the presence of nicotine with ion mobility spectrometry.

Methamphetamine (MA) is a highly addictive and illegal psychostimulant drug and is currently one of the most commonly abused illicit drugs in the world. The on-site rapid detection of trace amounts of MA and screening illicit drugs in clandestine laboratories is important for drug enforcement agencies and the forensic community in general. However, detecting methamphetamine in the presence of nicotine and cigarette smoke by ion mobility spectrometry faces difficulty due to the overlapped spectral peaks of methamphetamine and nicotine. In this work, a new method was developed to detect MA using pyridine as a dopant in the presence of nicotine by a homemade ion mobility spectrometry. The reduced mobilities of MA and nicotine were measured under the temperatures of the drift tube from 40 to 120 °C and doping with pyridine. The result shows that the temperature of 100 °C is beneficial to resolve the two substances. The concentration of doped pyridine is optimized to be 18 ppm. In this doped experiment, the reaction rate of nicotine is higher than that of MA by measuring the instrumental responses of MA and nicotine. No matter how high the nicotine content is, the interference of nicotine can be eliminated in the detection of MA doped with pyridine. This method is also successfully applied for the determination of MA and nicotine simultaneously in real saliva samples. The limit of detection of MA was measured to be about 0.5 ng/µL. The promising results in this work provide an effective method for on-site detection of MA.

Revealing Metabolic Perturbation Following Heavy Methamphetamine Abuse by Human Hair Metabolomics and Network Analysis.

Methamphetamine (MA) is a highly addictive central nervous system stimulant. Drug addiction is not a static condition but rather a chronically relapsing disorder. Hair is a valuable and stable specimen for chronic toxicological monitoring as it retains toxicants and metabolites. The primary focus of this study was to discover the metabolic effects encompassing diverse pathological symptoms of MA addiction. Therefore, metabolic alterations were investigated in human hair following heavy MA abuse using both targeted and untargeted mass spectrometry and through integrated network analysis. The statistical analyses (t-test, variable importance on projection score, and receiver-operator characteristic curve) demonstrated that 32 metabolites (in targeted metabolomics) as well as 417 and 224 ion features (in positive and negative ionization modes of untargeted metabolomics, respectively) were critically dysregulated. The network analysis showed that the biosynthesis or metabolism of lipids, such as glycosphingolipids, sphingolipids, glycerophospholipids, and ether lipids, as well as the metabolism of amino acids (glycine, serine and threonine; cysteine and methionine) is affected by heavy MA abuse. These findings reveal crucial metabolic effects caused by MA addiction, with emphasis on the value of human hair as a diagnostic specimen for determining drug addiction, and will aid in identifying robust diagnostic markers and therapeutic targets.

Assessment of contamination levels in methamphetamine-tested properties in New Zealand.

In November 2016, whilst in draft, the New Zealand Standard (NZS8510:2017) for the "Testing and Decontamination of Methamphetamine-Contaminated Properties" considered two acceptable post-decontamination re-occupancy methamphetamine levels; 1.5µg/100cm2 if the contamination was caused by smoking methamphetamine and 0.5µg/100cm2 if the contamination was caused by the manufacture of methamphetamine. In response to this, research carried out at this laboratory included the analysis of data obtained from over a thousand pre-decontamination property test reports with the aim of understanding the variation in the levels of contamination, that could be expected, among the wider New Zealand (contaminated) housing stock. The vast majority of the reports originated from public sector agency properties where methamphetamine was suspected to have been used. Although it could not be ruled-out, none of the properties had been associated with any suspicion of drug production. Thus, a further intention of the study was to assess and portray the levels of contamination that would be expected to be produced through methamphetamine use, commonly smoking. As such, it is expected that the data might be useful from an environmental exposure perspective and inform further research in this area. The assessment also discusses its potential as evidence in criminal cases where there may be discrepancies concerning the source of the methamphetamine contamination in relation to "Use of premises" and associated charges under Section 12 of the Misuse of Drugs Act (New Zealand) 1975. Regardless, the final New Zealand standard, released in June 2017, set a single decontamination level for 'high-use areas' of 1.5µg/100cm2 and a less stringent decontamination level for 'limited-use areas' of 3.8µg/100cm2, with no requirement to determine the origin of the contamination.

The Analysis of Aerosolized Methamphetamine From E-cigarettes Using High Resolution Mass Spectrometry and Gas Chromatography Mass Spectrometry.

The use of electronic cigarettes (e-cigs) has expanded from a nicotine delivery system to a general drug delivery system. The internet is rife with websites, blogs and forums informing users how to modify e-cigs to deliver illicit drugs while maintaining optimal drug delivery of their device. The goal of this study was to qualitatively identify the presence of methamphetamine in the aerosol produced by an e-cig and to quantitatively assess the effect voltage on the concentration of aerosolized methamphetamine. A KangerTech AeroTank electronic cigarette containing a 30, 60 or 120 mg/mL of methamphetamine in 50:50 propylene glycol: vegetable glycerin formulation was used to produce the aerosol. To qualitatively identify aerosolized methamphetamine, the aerosol was generated at 4.3 V, trapped in a simple glass trapping system, extracted using solid-phase microextraction (SPME), and analyzed by high-resolution Direct Analysis in Real Time AccuTOF™ Mass Spectrometry (DART-MS). To assess the effect of voltage on the concentration of aerosolized methamphetamine, the aerosol was generated at 3.9, 4.3 and 4.7 V, trapped and quantified using gas chromatography mass spectrometry (GC/MS). SPME-DART-MS and SPME-GC-MS demonstrated the aerosolization of methamphetamine. The concentration of aerosolized methamphetamine at 3.9, 4.3 and 4.7 V was not statistically different at 800 ± 600 ng/mL, 800 ± 600 ng/mL and 1,000 ± 800 ng/mL, respectively. The characterization of the vapors produced from e-liquids containing methamphetamine provides an understanding of the dose delivery dynamics of e-cigarettes.

Temperature dependent time resolved mid-IR photoacoustic spectroscopy of a nerve gas simulant DMMP.

The paper reports the temperature dependent pulsed photoacoustic spectroscopy of Dimethyl methylphosphonate (DMMP) a nerve gas simulant between 50 and 180 °C temperature range. The time domain PA spectra are recorded using two mid-IR wavelengths i.e. 3374 nm, 3495 nm of pulse duration 1.5 ns at 1 kHz repetition rate obtained from optical parametric oscillator. Two anti-symmetric stretching vibrational modes of (CH3P) and (CH3O) groups of DMMP molecules have very strong vibrational peaks at 2861.2 cm-1 (3495 nm) and 2963.8 cm-1 (3374 nm), respectively. In addition, we have also recorded the PA spectra of acetone at the vibrational frequency 3115.2 cm-1 (3210 nm), which is the strong vibrational mode of CH band. The comparison of two PA spectra of DMMP and acetone recorded using similar PA cavity help us to understand the effect of other functional groups with respect to different excitation wavelengths. The presence of additional acoustic modes in the PA spectra of DMMP (3374 nm) above the boiling point confirms the slow process of thermal decomposition. Finally, the low level detection limit of DMMP in air is of the of the order of 0.91 ppbV.

Analysis of N,N-dimethylamphetamine in wastewater - a pyrolysis marker and synthesis impurity of methamphetamine.

The increased availability of high purity crystalline methamphetamine (MA) in Australia raised concerns because of high dosages and its potential consumption through inhalation. The present work investigates the possibility of using wastewater levels of N,N-dimethylamphetamine (DMA), a pyrolysis by-product, as an indirect indicator of MA smoking. A dedicated liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QToF-MS) method was set up to detect and quantify DMA in wastewater samples. Wastewater samples were collected from 8 locations across Australia during the period 2011-2016. Data about the abundance of DMA in MA seizures as well as in residues from drug paraphernalia were obtained from forensic laboratories in Australia. DMA/MA ratios measured in wastewater ranged from 0.0001 to 0.09 (median 0.007). DMA/MA ratios in bulk seizures are generally below 0.0025, with a median value of 0.0004, whilst residues in paraphernalia ranged from 0.031 to 3.37. DMA/MA ratios in wastewater decreased between 2011 and 2016, in parallel to an increase in MA loads. Furthermore, wastewater analyses highlighted a strong positive correlation between DMA/MA ratios and per capita MA use (Pearson's correlation ρ= 0.61, p-value <0.001). Nonetheless, geographical specificities could be highlighted between the investigated locations. The obtained data could help authorities detect hot spots of drug use as well as to plan specific intervention campaigns to tackle the issue. In future, simultaneous analysis of DMA and MA in both wastewater and seizures could improve our understanding about MA use and its consumption patterns.

Characterisation of aqueous waste produced during the clandestine production of amphetamine following the Leuckart route utilising solid-phase extraction gas chromatography-mass spectrometry and capillary electrophoresis with contactless conductivity detection.

Chemical waste from the clandestine production of amphetamine is of forensic and environmental importance due to its illegal nature which often leads to dumping into the environment. In this study, 27 aqueous amphetamine waste samples from controlled Leuckart reactions performed in Germany, the Netherlands, and Poland were characterised to increase knowledge about the chemical composition and physicochemical characteristics of such waste. Aqueous waste samples from different reaction steps were analysed to determine characteristic patterns which could be used for classification. Conductivity, pH, density, ionic load, and organic compounds were determined using different analytical methods. Conductivity values ranged from 1 to over 200 mS/cm, pH values from 0 to 14, and densities from 1.0 to 1.3 g/cm3 . A capillary electrophoresis method with contactless conductivity detection (CE-C4 D) was developed and validated to quantify chloride, sulphate, formate, ammonium, and sodium ions which were the most abundant ions in the investigated waste samples. A solid-phase extraction sample preparation was used prior to gas chromatography-mass spectrometry analysis to determine the organic compounds. Using the characterisation data of the known samples, it was possible to assign 16 seized clandestine waste samples from an amphetamine production to the corresponding synthesis step. The data also allowed us to draw conclusions about the synthesis procedure and used chemicals. The presented data and methods could support forensic investigations by showing the probative value of synthesis waste when investigating the illegal production of amphetamine. It can also act as starting point to develop new approaches to tackle the problem of clandestine waste dumping.

Resolution of isomeric new designer stimulants using gas chromatography - Vacuum ultraviolet spectroscopy and theoretical computations.

Distinguishing isomeric representatives of "bath salts", "plant food", "spice", or "legal high" remains a challenge for analytical chemistry. In this work, we used vacuum ultraviolet spectroscopy combined with gas chromatography to address this issue on a set of forty-three designer drugs. All compounds, including many isomers, returned differentiable vacuum ultraviolet/ultraviolet spectra. The pair of 3- and 4-fluoromethcathinones (m/z 181.0903), as well as the methoxetamine/meperidine/ethylphenidate (m/z 247.1572) triad, provided very distinctive vacuum ultraviolet spectral features. On the contrary, spectra of 4-methylethcathinone, 4-ethylmethcathinone, 3,4-dimethylmethcathinone triad (m/z 191.1310) displayed much higher similarities. Their resolution was possible only if pure standards were probed. A similar situation occurred with the ethylone and butylone pair (m/z 221.1052). On the other hand, majority of forty-three drugs was successfully separated by gas chromatography. The detection limits for all the drug standards were in the 2-4 ng range (on-column amount), which is sufficient for determinations of seized drugs during forensics analysis. Further, state-of-the-art time-dependent density functional theory was evaluated for computation of theoretical absorption spectra in the 125-240 nm range as a complementary tool.

The persistence of illicit drug smoke residues and their recovery from common household surfaces.

Third-hand smoke is the residue remaining on surfaces during smoking events. It is composed of particles and vapours that form upon heating. The phrase 'third-hand smoke' is primarily used to describe nicotine and other chemicals from cigarettes, but any residues formed from the smoking of various substances could be classified similarly. There has been an increasing body of research on third-hand smoke from cigarettes in the last decade, but little has been done in regards to understanding the persistence of particles and vapours from illicit drugs. In this work, small samples of cocaine and methamphetamine were volatilized to produce an illicit drug smoke that was collected onto various surface materials and left exposed to ambient conditions over 672 h (four weeks). Chemical analyses by electrospray ionization-mass spectrometry of residues on silicon, plastic, laminate, and artificial leather surfaces indicated a rapid decrease in recovery of the parent molecule, with varied formation of decomposition products over the first 168 h of exposure. Measurable amounts of the parent molecule were still present after 672 h, exhibiting a strong persistence of these drugs on various household materials. This is important in a forensic science context, as third-hand smoke residues could provide a viable source of trace evidence previously not utilized. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels in wastewater with sale, seizure and consumption data for 8 European cities.

BACKGROUND: Monitoring the scale of pharmaceuticals, illicit and licit drugs consumption is important to assess the needs of law enforcement and public health, and provides more information about the different trends within different countries. Community drug use patterns are usually described by national surveys, sales and seizure data. Wastewater-based epidemiology (WBE) has been shown to be a reliable approach complementing such surveys. METHOD: This study aims to compare and correlate the consumption estimates of pharmaceuticals, illicit drugs, alcohol, nicotine and caffeine from wastewater analysis and other sources of information. Wastewater samples were collected in 2015 from 8 different European cities over a one week period, representing a population of approximately 5 million people. Published pharmaceutical sale, illicit drug seizure and alcohol, tobacco and caffeine use data were used for the comparison. RESULTS: High agreement was found between wastewater and other data sources for pharmaceuticals and cocaine, whereas amphetamines, alcohol and caffeine showed a moderate correlation. methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) and nicotine did not correlate with other sources of data. Most of the poor correlations were explained as part of the uncertainties related with the use estimates and were improved with other complementary sources of data. CONCLUSIONS: This work confirms the promising future of WBE as a complementary approach to obtain a more accurate picture of substance use situation within different communities. Our findings suggest further improvements to reduce the uncertainties associated with both sources of information in order to make the data more comparable.

Evaluation of the efficiency of continuous wavelet transform as processing and preprocessing algorithm for resolution of overlapped signals in univariate and multivariate regression analyses; an application to ternary and quaternary mixtures.

Wavelets have been adapted for a vast number of signal-processing applications due to the amount of information that can be extracted from a signal. In this work, a comparative study on the efficiency of continuous wavelet transform (CWT) as a signal processing tool in univariate regression and a pre-processing tool in multivariate analysis using partial least square (CWT-PLS) was conducted. These were applied to complex spectral signals of ternary and quaternary mixtures. CWT-PLS method succeeded in the simultaneous determination of a quaternary mixture of drotaverine (DRO), caffeine (CAF), paracetamol (PAR) and p-aminophenol (PAP, the major impurity of paracetamol). While, the univariate CWT failed to simultaneously determine the quaternary mixture components and was able to determine only PAR and PAP, the ternary mixtures of DRO, CAF, and PAR and CAF, PAR, and PAP. During the calculations of CWT, different wavelet families were tested. The univariate CWT method was validated according to the ICH guidelines. While for the development of the CWT-PLS model a calibration set was prepared by means of an orthogonal experimental design and their absorption spectra were recorded and processed by CWT. The CWT-PLS model was constructed by regression between the wavelet coefficients and concentration matrices and validation was performed by both cross validation and external validation sets. Both methods were successfully applied for determination of the studied drugs in pharmaceutical formulations.

Immunohistochemical localization of anterior pituitary cell types of vervet monkey (Chlorocebus aethiops) following sub-chronic cathinone exposure.

ETHNOPHARMACOLOGICAL RELEVANCE: Khat (Catha edulis) contains cathinone, an active principal that is customarily used as a psychostimulant that wards off fatigue and to some extent used as an aphrodisiac. AIM OF STUDY: To investigate effects of escalating doses of cathinone on hormone expression by different anterior pituitary cell types using specific antibodies. MATERIAL AND METHODS: Eleven vervet monkeys (6 males and 5 females) divided into tests (n=9) and controls (n=2) were used. Animals were allocated as group I (saline controls), group II (0.8 mg/kg), group III (3.2 mg/kg) and group IV (6.4 mg/kg) of cathinone. All treatments were via oral route at alternate days of each week. At the end of 4-month treatment phase, GnRH agonist (ZOLADEX) was administered to group II (low dose) and group IV (high dose) alongside cathinone for 2 additional weeks. RESULTS: High cathinone dose at long-term exposure caused proliferation of gonadotrophs but decrease in lactotrophs and corticotrophs in anterior pituitary sections of animals while effect of low dose on these cells was insignificant. Subsequent GnRH agonist co-treatment with low and high cathinone doses enhanced gonadotroph proliferation but no change on decline of lactotrophs and corticotrophs. CONCLUSION: We believe that there was a possible potentiation of cathinone on pituitary hormone synthesis thereby influencing reproductive function. Suppression of corticotrophic and lactotrophic functions suggest lowering of stress levels and modulation of reproductive function based on dose level and chronicity of exposure. The findings are consistent with the hypothesis that cathinone interferes with pituitary cell integrity and consequently target organs, but further studies are required to address the precise mechanism underlying this phenomenon.

Pathologic manifestations of levamisole-adulterated cocaine exposure.

Rheumatic manifestations of cocaine have been well described, but more recently, a dramatic increase in the levamisole-adulterated cocaine supply in the United States has disclosed unique pathologic consequences that are distinct from pure cocaine use. Most notably, patients show skin lesions and renal dysfunction in the setting of extremely high perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). Unexpectedly, antibodies to myeloperoxidase, the typical target of p-ANCA, are relatively low if at all present. This discrepancy is due to the fact that p-ANCA seen in association with levamisole-adulterated cocaine exposure is often directed against atypical p-ANCA-associated antigens within the neutrophil granules such as human neutrophil elastase, lactoferrin, and cathepsin G. Biopsies of the skin lesions reveal leukocytoclastic vasculitis often involving both superficial and deep dermal vessels. Renal injury most typically manifests as crescentic and necrotizing pauci-immune glomerulonephritis. In this review, the manifestations of levamisole-adulterated cocaine-induced vasculitis are discussed with an emphasis on the typical histomorphologic findings seen on biopsy. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1764738711370019 .

Identification of black market products and potential doping agents in Germany 2010-2013.

PURPOSE: The desire to increase the athletic performance, to 'optimize' an individual's appearance, and to complement but also to arguably substitute exercise by means of drugs and drug candidates has generated a considerable (illicit) market for compounds such as anabolic-androgenic steroids, stimulants, growth promoting peptide hormones, and so on. Genuinely developed for therapeutic use, their abuse/misuse generates enormous health risks, which has necessitated comprehensive controls of compound trafficking by customs and anti-doping authorities. METHODS: From 2012 to 2013, the Bureau of Customs Investigation confiscated products containing anabolic-androgenic steroids (AAS; 259 kg), stimulants (13 kg), selective estrogen receptor modulators (SERMs; 24 kg), and human growth hormone (hGH; 3500 ampules). In cooperation with the Bureau and under the umbrella of the European Monitoring Center for Emerging Doping Agents (EuMoCEDA), the Cologne Anti-Doping Laboratory analyzed an additional 337 (black market) products between 2010 and 2013, allowing to monitor developments in drug use and, hence, the anticipation of new challenges in sports drug testing. Main tools utilized in characterizing confiscated materials were liquid chromatography-high resolution mass spectrometry (LC-HRMS), gas chromatography-high resolution mass spectrometry (GC-HRMS), and polyacrylamide gel electrophoresis (PAGE) with subsequent bottom-up identification of peptidic compounds using nano liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). RESULTS: Among the 337 substances analyzed in the doping control laboratory in Cologne, 67 active ingredients were found, 49 of which being categorized as doping agents by the World Anti-Doping Agency (WADA). A total of 83.7 % accounted for steroidal substances (predominantly testosterone, trenbolone, and nandrolone and corresponding esters), 12.8 % accounted for peptide hormones and growth factors (predominantly hGH and growth hormone releasing peptides (GHRPs)), 3.2 % of the products contained hormones and metabolic modulators, and 0.3 % accounted for diuretic agents. Outstanding findings were the detection of the selective androgen receptor modulator (SARM) LGD-4033, the thymic hormone thymosin ß4, and a fusion protein of unknown biological activity. CONCLUSIONS: Trafficking of considerable amounts of arguably performance and/or body-enhancing compounds has been observed during the past 4 years, the majority of which is categorized as relevant to sports drug testing. Several substances are of fake/non-approved nature and represent enormous health risks to the 'customer'.

Fatal oral methylphenidate intoxication with postmortem concentrations.

Methylphenidate (MPD) is a widely prescribed stimulant used primarily for the treatment for attention-deficit/hyperactivity disorder (ADHD). Suicide attempts involving MPD ingestion have been well described; however, deaths attributed solely to MPD ingestion have not been reported. A 62-year-old woman was found dead on her floor. The only discrepancy in among her medication quantities was that >three hundred 10 mg MPD tablets were missing. Analysis utilizing gas chromatography-mass spectrometry revealed elevated postmortem MPD peripheral and central blood, liver and vitreous humor concentrations. Considering both the central blood to peripheral blood ratio (0.89) and the liver to peripheral blood ratio (3.3), MPD does not appear subject to significant postmortem redistribution. With no other identifiable cause of death, we report what appears to be the first isolated MPD ingestion associated with a fatality.

Acute methylone intoxication in an accidental drowning--a case report.

A 19-year-old woman who was known to use illicit drugs (ecstasy and marijuana) was found floating in the ocean 100 yards from the beach. When last seen the previous evening, she had said to a friend that she was going to "get in the water." Reports to police indicated that she "may have been on ecstasy." There were no notes of a suicidal nature, illicit drugs, drug paraphernalia, tobacco cigarettes, or alcoholic beverages at the scene. Autopsy findings were consistent with drowning. Postmortem blood initially screened positive for methamphetamine and cannabinoids by ELISA and was subsequently confirmed for methylone by a specific GC-MS SIM analysis following solid-phase extraction. Concentrations found in the peripheral blood, central blood, vitreous, liver and gastric contents were measured at 3.4 mg/L 3.4 mg/L, 4.3mg/L, 11 mg/kg, and 1.7 mg, respectively. No other amphetamine-like compound (including ecstasy) was detected. These results are discussed in relation to previous cases of toxicity, and the lack of potential for substantial methylone postmortem redistribution.

Segmental hair analysis and estimation of methamphetamine use pattern.

The aim of this study was to investigate whether the results of segmental hair analysis can be used to estimate patterns of methamphetamine (MA) use. Segmental hair analysis for MA and amphetamine (AP) was performed. Hair was cut into the hair root, consecutive 1 cm length segments and 1-4 cm length segments. Whole hair was also analyzed. The hair samples were incubated for 20 h in 1 mL methanol containing 1 % hydrochloric acid after washing the hair samples. Hair extracts were evaporated and derivatization was performed using trifluoroacetic anhydride in ethylacetate at 65 °C for 30 min. Derivatized extract was analyzed by gas chromatography/mass spectrometry. The 15 subjects consisted of 13 males and two females and their ages ranged from 25 to 42 (mean, 32). MA and AP concentrations in the whole hair ranged from 3.00 to 105.10 ng/mg (mean, 34.53) and from 0.05 to 4.76 ng/mg (mean, 2.42), respectively. Based on the analysis of the 1 cm length segmental hair, the results were interpreted in a way to distinguish between continuous use of MA (n = 10), no recent but previous use of MA (n = 3), and recent but no previous use of MA (n = 2). Furthermore, the individuals were interpreted as light, moderate, and heavy users based on concentration ranges previously published.

Determination of stimulants using gas chromatography/high-resolution time-of-flight mass spectrometry and a soft ionization source.

RATIONALE: The aim of this study was to investigate the mass spectral fragmentation of a small set of stimulants in a high-resolution time-of-flight mass spectrometer equipped with a soft ionization source using vacuum ultraviolet (VUV) photons emitted from different plasma gases. It was postulated that the use of a plasma gas such as Xe, which emits photons at a lower energy than Kr or Ar, would lead to softer ionization of the test compounds, and thus to less fragmentation. METHODS: A set of nine stimulants: cocaine, codeine, nicotine, methadone, phenmetrazine, pentylenetetrazole, niketamide, fencamfamine, and caffeine, was analyzed by gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) in positive ion mode with this soft ionization source, using either Xe, Kr, or Ar as plasma gases. Working solutions of the test compounds at 0.1 to 100 ng/µL were used to establish instrument sensitivity and linearity. RESULTS: All test compounds, except methadone and pentylenetetrazole, exhibited strong molecular ions and no fragmentation with Xe-microplasma photoionization (MPPI). Methadone exhibited significant fragmentation not only with Xe, but also with Kr and Ar, and pentylenetetrazole could not be ionized with Xe, probably because its ionization energy is above 8.44 eV. The Kr- and Ar-MPPI mass spectra of the test compounds showed that the relative intensity of the molecular ion decreased as the photon energy increased. CONCLUSIONS: When coupled to a TOF mass spectrometer this soft ionization source has demonstrated signal-to-noise (S/N) ratios from 7 to 730 at 100 pg per injection (depending on the compound), and a dynamic range of three orders of magnitude (100 pg to 100 ng) for some of the test compounds.