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ABSTRACT: Indian hemp is used since thousands of years as herbal drug. We found that a single dose of cannabis resin was equally active as Δ9-tetrahydrocannabinol (THC) enhancing severity and duration of symptoms in vaccinia virus infected mice. Cowpox virus did not cause symptomatic disease, but some reduction of specific antibody production was observed in drug treated animals. In vitro cannabis was superior to THC alone at inhibiting mitogen stimulated proliferation of human and mouse spleen cells and peripheral blood mononuclear cells. Also resin sub-fractions other than THC, cannabidiol and cannabinol, recovered also from cigarette smoke, were found inhibitory, suggesting additional involvement of constituents other than psychoactive THC. The immunoregulatory effects must be differentiated from apoptotic effects on spleen cells and lymphocytic mouse cell lines, which were observed with resin and THC but not with cannabidiol or cannabinol. A significant contribution of cytotoxic effects seems unlikely as drug treated lymphocytes were still capable of producing cytokines after T-cell receptor-specific stimulation. Considering a recent case of unusually severe cowpox virus infection in a young drug taker these data confirm a risk of "soft drugs" for acquiring poxvirus infection or enhancing side effects of the smallpox vaccine and perhaps also other live vaccines.
Immunobiology 11/2010; 216(6):670-7. · 3.20 Impact Factor
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ABSTRACT: Topiramate belongs to a new group of anticonvulsive drugs primarily applied in treatment of epilepsy and in preventive therapy of migraines. Topiramate is structurally unrelated to other antiepileptic drugs and acts by multiple neurostabilizing mechanisms. However, the pharmacology of topiramate appears to be complex and some of its pharmacodynamic actions still remain to be elucidated. This case report documents a fatal intoxication involving topiramate. A 41-year old woman with a known history of psychiatric disorder was found unresponsive by her husband. Resuscitation efforts did not succeed and the woman was pronounced dead at the intensive care unit four hours later. At the scene, drug packages of topiramate, citalopram and flunitrazepam were found. Autopsy including histological examination revealed morphological signs of an acute intoxication and shock. A comprehensive toxicological analysis with GC-MS was performed on the deceased's autopsy samples (femoral blood, bile, kidney, gastric content). The results revealed the presence of topiramate at a concentration of 49mg/L in the femoral blood sample, thus clearly exceeding the therapeutic range. Additionally, citalopram (0.85mg/L) and flunitrazepam in traces (<2μg/L) were detected in peripheral blood. Based on the autopsy findings and toxicological results, the cause of death was primarily attributed to an intoxication with topiramate in combination with citalopram.
Forensic science international 10/2010; 202(1-3):e9-11. · 2.10 Impact Factor
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ABSTRACT: Benzodiazepines are drugs widely used as tranquilizers and in various other indications. We treated Balb/c mice with diazepam and infected them with cowpox (CPXV) and vaccinia virus (VACV). Disease index, weight loss and the antibody response were determined. Additionally the influence of different benzodiazepines on the mitogen response of human peripheral blood lymphocytes and spleen cells was tested. Diazepam led to earlier disease onset, prolonged duration of symptoms, higher weight loss and overall disease index in VACV infected mice. CPXV infected mice developed poxviral skin lesions only after drug administration and a significant decrease in the specific antibody response was also observed. Diazepam and alprazolam also inhibited the proliferative response of human lymphocytes/spleen cells in vitro but did not show noteworthy apoptotic effects. It is surprising that even a single dose of diazepam has a profound influence on the immune system, sufficient to facilitate symptomatic infectious disease. These data provide first evidence that commonly used drugs like Valium may augment severity of rare poxvirus infections such as CPXV or monkeypox. As VACV is still used as life vaccine against smallpox there is also a risk of enhanced side effects or possible interference with the success of vaccination.
Vaccine 08/2010; 28(38):6152-8. · 3.77 Impact Factor
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ABSTRACT: A convenient mass spectrometric approach for the identification of toxicologically relevant compounds in tablets and tablet residues is presented. For comprehensive forensic-toxicological analysis electrospray ionization mass spectrometry was accomplished in positive as well as in negative ion mode on a quadrupole-quadrupole-time-of-flight instrument. Dissolved samples were introduced into the mass spectrometer by flow-injection. Mass spectra as well as tandem mass spectra were acquired. A data-dependent acquisition strategy was used to switch between the mass spectrometric modes. Identification was accomplished via search within a tandem mass spectral library. The applied database contained 8252 spectra collected from 836 compounds in positive ion mode as well as 1023 spectra collected from 103 compounds in negative ion mode. A total of 22 casework samples collected during autopsies from mouth, oesophagus or gastric contents, seized by the police, or found with patients at hospital were screened. Twelve samples contained compounds only detectable in positive ion mode (sildenafil, dihydrocodeine, diphenhydramine, oxprenolol, N-methyl-3,4-methylenedioxyamphetamine, morphine, amphetamine, caffeine, pemoline, orphenadrine, m-chlorphenylpiperazine and tramadol), six samples contained species exclusively detectable in negative ion mode (salicylic acid, acetylsalicylic acid, ibuprofen, ketorolac, valproic acid and phenobarbital), and three samples contained diclofenac detectable in both ionization polarities. One sample did not contain any compound amenable to mass spectrometric analysis. For verification all samples were additionally analyzed by GC/MS. Both methods revealed identical results for all but one sample. The beta-adrenergic blocker oxprenolol was exclusively detected by the flow-injection method.
Forensic science international 04/2010; 197(1-3):40-7. · 2.10 Impact Factor
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ABSTRACT: A well-established possibility to treat opiate addiction is the participation in opiate maintenance treatment programmes. For this purpose the opioids methadone and buprenorphine have been evaluated and are used nowadays in many countries. However, since 1998 also the use of slow-release oral morphine (SROM) has been legally permitted in Austria. Our data show that these morphine preparations are frequently abused and are dominating the black market in the meantime. Especially the intravenous consumption of SROM goes along with highly dangerous side effects that exceed the risks of needle sharing alone. Special galenics are supposed to ensure a 24 h effect of the otherwise quickly metabolised morphine. If dissolved and injected, insoluble contents such as talcum cause microembolisms, leading to severe damages of the inner organs. Furthermore, SROM, i.e. a drug prescribed by physicians, has been proved to be the main responsible substance in most drug related deaths since its permission and has nearly replaced heroin. Forensic physicians play a major role in the profound examination of these cases, including extensive toxicological analyses and interpretation of results. For instance, a differentiation between a recent morphine and heroin consumption is certainly possible, provided appropriate methods are used. A reliable estimation of the current situation of drug abusing habits is a premise for adequate therapeutic offers and preventive measures. Thus, well-founded and comparable data have to be collected. To facilitate data report a standardized report form has been developed that includes an obligatory statement regarding morphine or heroin consumption. This should help to enlighten the ongoing discussion on the role of SRM in drug abuse cases. Our results indicate that the prescription of SROM in opiate maintenance therapy has to be handled very strictly and should be reserved for special patients only. A slackening of the Austrian law concerning SROM is therefore objected.
Neuropsychiatrie: Klinik, Diagnostik, Therapie und Rehabilitation: Organ der Gesellschaft Österreichischer Nervenärzte und Psychiater 01/2010; 24(2):108-17. · 1.38 Impact Factor
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ABSTRACT: Bioartificial liver (BAL) systems can take over liver functions in patients undergoing liver failure until transplantation. Recently, a novel prototype rotary BAL has been developed using small human hepatocytes (SH). This study investigated the metabolism of opiates morphine and methadone in the BAL and their influence on the basic cell culture parameters, viability, and growth of SH. Opiates may be present in patients due to pain therapy, anticancer treatment, or drug abuse. Cells were cultivated in the BAL for a total of 12 days and exposed twice to 100 microg/L of morphine or methadone. Morphine and methadone concentrations were analyzed using gas chromatography with a mass spectrometry detector. Further, the production of albumin, lactate dehydrogenase release, lactate release, urea production, and glucose consumption were measured. Cell viability and growth were determined by confocal microscopy. Cytochrome P 3A4 and uridindiphosphat (UDP) glucuronosyl transferase 2B7 in SH were analyzed by western blot. The mean cell density during treatment was 5.5 +/- 0.7 x 10(6) cells/mL (n = 6) and was not altered significantly by the opiates. Cell viability stayed above 90%. Morphine was not reduced by SH and was a stress factor as determined by decreased metabolic activity. On the other hand, SH metabolized methadone showing first-order kinetics: the first-order rate constant k = 0,019, half-life t(1/2) = 36 h. Methadone metabolism led to decreased urea and albumin production. The expression of cytochrome P 3A4, mainly responsible for methadone metabolism, was proved in SH. The prototype BAL is basically suited to support liver functions, provided patients receive therapy with methadone.
Tissue Engineering Part A 09/2009; 16(3):807-13. · 4.64 Impact Factor
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ABSTRACT: The inter-instrument and inter-laboratory transferability of a tandem mass spectral reference library originally built on a quadrupole-quadrupole-time-of-flight instrument was examined. The library consisted of 3759 MS/MS spectra collected from 402 reference compounds applying several different collision-energy values for fragmentation. In the course of the multicenter study, 22 test compounds were sent to three different laboratories, where 418 tandem mass spectra were acquired using four different instruments from two manufacturers. The study covered the following types of tandem mass spectrometers: quadrupole-quadrupole-time-of-flight, quadrupole-quadrupole-linear ion trap, quadrupole-quadrupole-quadrupole, and linear ion trap-Fourier transform ion cyclotron resonance mass spectrometer. In each participating laboratory, optimized instrumental parameters were gathered solely from routinely applied workflows. No standardization procedure was applied to increase the inter-instrument comparability of MS/MS spectra. The acquired tandem mass spectra were matched against the established reference library using a sophisticated matching algorithm, which is presented in detail in a companion paper. Correct answers, meaning that the correct compound was retrieved as top hit, were obtained in 98.1% of cases. For the remaining 1.9% of spectra, the correct compound was matched at second rank. The observed high percentage of correct assignments clearly suggests that the developed mass spectral library search approach is to a large extent platform independent.
Biological Mass Spectrometry 01/2009; 44(4):485-93. · 3.41 Impact Factor
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ABSTRACT: A sophisticated matching algorithm developed for highly efficient identity search within tandem mass spectral libraries is presented. For the optimization of the search procedure a collection of 410 tandem mass spectra corresponding to 22 compounds was used. The spectra were acquired in three different laboratories on four different instruments. The following types of tandem mass spectrometric instruments were used: quadrupole-quadrupole-time-of-flight (QqTOF), quadrupole-quadrupole-linear ion trap (QqLIT), quadrupole-quadrupole-quadrupole (QqQ), and linear ion trap-Fourier transform ion cyclotron resonance mass spectrometer (LIT-FTICR). The obtained spectra were matched to an established MS/MS-spectral library that contained 3759 MS/MS-spectra corresponding to 402 different reference compounds. All 22 test compounds were part of the library. A dynamic intensity cut-off, the search for neutral losses, and optimization of the formula used to calculate the match probability were shown to significantly enhance the performance of the presented library search approach. With the aid of these features the average number of correct assignments was increased to 98%. For statistical evaluation of the match reliability the set of fragment ion spectra was extended with 300 spectra corresponding to 100 compounds not included in the reference library. Performance was checked with the aid of receiver operating characteristic (ROC) curves. Using the magnitude of the match probability as well as the precursor ion mass as benchmarks to rate the obtained top hit, overall correct classification of a compound being included or not included in the mass spectrometric library, was obtained in more than 95% of cases clearly indicating a high predictive accuracy of the established matching procedure.
Biological Mass Spectrometry 01/2009; 44(4):494-502. · 3.41 Impact Factor
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ABSTRACT: The metabolic transformation pathways of the 1,4-benzodiazepine tetrazepam (C(16)H(17)ClN(2)O, average mass: 288.772) were studied with capillary LC-QqTOF-MS and -MS/MS by analyzing human plasma and urine samples collected from healthy volunteers. Each volunteer took 50 mg of tetrazepam, given in the form of one tablet of Myolastan (Sanofi-Synthelabo, Vienna, Austria). Accurate molecular mass measurements in full-scan mode (scan range: 50-700) were used to survey the collected samples for putative metabolic transformation products. Full-scan fragment ion mass spectra were collected in subsequent LC/MS/MS experiments. Each spectrum was matched to a spectral library containing 3759 MS/MS-spectra of 402 compounds, including eighteen different benzodiazepines, to prove the structural relatedness of a tentative metabolite to tetrazepam. This "similarity search" approach provided a rapid and powerful tool to exclude non-drug-related species, even without any knowledge of the fragmentation chemistry. Interpretation of tandem mass spectrometric data was only required in order to elucidate the site of transformation. Using this strategy, 11 major classes of tetrazepam metabolites were identified. Possible metabolic routes from tetrazepam to diazepam (C(16)H(13)ClN(2)O, average mass: 284.740) via repeated hydroxylation and dehydration of the cylohexenyl moiety were discovered. No evidence for extensive hydroxylation of tetrazepam at position 3 of the diazepine ring was found. In contrast to what is commonly believed, this distinct transformation reaction may be of only minor importance. Furthermore, the occurrence of demethylation, hydration, and glucuronidation reactions was proven.
Analytical and Bioanalytical Chemistry 11/2008; 392(7-8):1299-308. · 3.78 Impact Factor
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ABSTRACT: Legal driving limits are set coequally with 0.5 g/L blood alcohol concentration (BAC) or 0.25 mg/L breath alcohol concentration (BrAC) in Austria as well as in other European countries. As mostly some time elapses between BrAC measurement and driving offence, a back calculation of alcohol concentrations is often required. The calculation of hourly BrAC elimination rates can thereby help to avoid unnecessary variances. A study with 59 participants was performed under social conditions. BrAC was determined with the legally accredited Alcotest 7110 MK III A every 30 min, and concomitantly venous blood samples were drawn. Five hundred and four BrAC/BAC value pairs were evaluated. The overall mean peak BrAC was calculated with 0.456 mg/L (+/-0.119 mg/L standard deviation). The mean hourly BrAC elimination rate was overall determined with 0.082 mg/L per h (0.050-0.114, 95% range). Mean rate of females (0.087 mg/L h(-1)) and the according 95% limits were statistically significantly higher than of males (mean rate 0.078 mg/L h(-1), p<0.04). Our results confirm the possibility to implement hourly BrAC elimination rates, provided that adequate statistical ranges and basic forensic scientific rules that have been set up for alcohol back calculations are observed.
Forensic science international 08/2007; 171(1):16-21. · 2.10 Impact Factor
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ABSTRACT: The benzodiazepine tetrazepam is primarily muscle relaxant with comparably lower central sedating effects and is therefore commonly prescribed for muscle spasms of different origins. To evaluate tetrazepam metabolism, a study was conducted with ten healthy volunteers. Blood and urine samples were regularly collected after the intake of 50 mg tetrazepam. Toxicological analyses revealed that tetrazepam is also metabolized to diazepam and further to nordazepam, which has not yet been reported. Tetrazepam and diazepam could be detected in urine samples at least 72 h after intake, the diazepam concentration being 33% (+/-14% SD), on average, of the tetrazepam concentration. On the basis of three case histories, the importance of the detection of these newly described metabolites is shown as necessary to prevent false accusations and potential negative legal consequences for examined persons.
Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 06/2007; 121(3):169-74. · 2.59 Impact Factor
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ABSTRACT: Current approaches to support alcohol addict and/or benzodiazepine-treated patients with liver failure include culturing human cells to take over basic metabolic functions for a certain time.
Small human hepatocytes (SH) were grown in a rotary cell culture system, and their potential to metabolize alcohol and the benzodiazepines oxazepam and diazepam was evaluated. Control experiments were performed with SV40-immortalized HEP cells and cell respective drug-free media.
Our results show that SH in rotary culture are able to metabolize ethanol in reasonable amounts compared with evaporation controls (p<0.01). Moreover, SH are also able to metabolize oxazepam and diazepam which proves their ability to perform conjugation and the presence of functional cytochrome P450 enzymes. Basic metabolic activities such as glucose consumption, albumin and urea production are not significantly influenced by the drugs used, which is a precondition for clinical use of these cells. Significantly increased lactate dehydrogenase release indicates enhanced cell death in cultures of SH incubated with either ethanol (p<0.05) or diazepam (p<0.005), but stable viability at or above 90% suggests that cell proliferation is able to keep up with drug-induced cell death.
Our preliminary study provides evidence that SH are basically suited to support alcohol-abusing and/or benzodiazepine-treated patients undergoing liver failure.
Alcoholism Clinical and Experimental Research 06/2007; 31(5):729-36. · 3.34 Impact Factor
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ABSTRACT: The European DNA profiling group (EDNAP) mtDNA population database (EMPOP) is an international collaborative project between DNA laboratories performing mtDNA analysis and the DNA laboratory of the Institute of Legal Medicine (GMI) in Innsbruck, Austria. The goal is to set up a directly accessible mtDNA population database, which can be used in routine forensic casework for frequency investigations. Here we describe a safe laboratory scheme involving electronical data handling and computer-aided data transfer, which help to minimize errors originating from potential sample mix-up, data misinterpretation and incorrect transcription. The procedure is demonstrated by example of an mtDNA control region population study on 273 unrelated individuals from Austria. Our population sample was compared with five other European populations via an analysis of molecular variance (AMOVA). The inclusion of regions outside HVS-I and HVS-II increased the amount of information on the haplogroup diagnostic sites in the control region. Most of the haplotypes in Austrians fell into haplogroups H, J, K, T, and U. The random match probability in Austrians was 1:125; the average number of nucleotide differences between individuals in the Austrian database was 9.32.
Forensic Science International 04/2007; 166(2-3):164-75. · 2.30 Impact Factor
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ABSTRACT: We developed a modular real-time (rt) PCR system for absolute quantification of human nuclear (n) and mitochondrial (mt) DNA. For determination of the number of amplifiable template molecules with a minimum length required for downstream genotyping and assessment of the PCR-relevant degradation grade of the template DNA, primers yielding differently sized PCR products (nDNA: 79, 156, and 246 bp; mtDNA: 102, 143, 283, and 404 bp) and TaqMan hybridization probes were used for amplification and on-line product detection. DNase-degraded DNA served as model to demonstrate the effects of DNA fragmentation on rtPCR quantification and subsequent genotyping. Introduction of cloned internal amplification positive controls (IPCs)--generated by in vitro mutagenesis of primer-binding sites of the wild-type nDNA and mtDNA targets--enabled functionality-testing of the reaction mixture and detection of PCR inhibitors in DNA extracts, without a need for additional TaqMan probes. A hematin model was used to test the ability of the quantitative real-time (rtq) PCR system to predict the effects of inhibitors in downstream PCR-based genotyping.
Forensic science international. Genetics 04/2007; 1(1):29-34. · 2.42 Impact Factor
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ABSTRACT: Most cases of ecstasy overdose turn out to be accidental, whereas suicide attempts with designer drugs occur only sporadically. We report an announced suicide by means of a combination of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA). During autopsy, sampling for toxicological investigation (peripheral blood, urine, cerebrospinal fluid, bile and gastric contents) occurred. Serum concentrations as high as 13.33 mg/l for MDMA, 7.32 mg/l for MDEA and 0.43 mg/l for 3,4-methylenedioxyamphetamine were found. Ecstasy tablets, which were confiscated by the police a few days earlier, showed also a combination of MDMA and MDEA. This fact suggests that the ingested tablets probably came from the same source as the seized pills.
Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 02/2007; 121(1):40-3. · 2.59 Impact Factor
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ABSTRACT: Several products are being widely promoted for reduction of the concentration of alcohol in the human body. One of these preparations, the fructose soft drink Outox, claims to noticeably increase the alcohol elimination rate (beta 60). Theories to explain this 'fructose effect' are based on the assumption that NAD+, the coenzyme for alcohol dehydrogenase, is regenerated faster in the presence of fructose.
A randomized double-blind, placebo-controlled cross-over study was performed with 30 volunteers in two drinking sessions each. Under strictly identical conditions, the same amount of alcohol was consumed, followed by the consumption of either 250 ml Outox or 250 ml placebo. Periodical measurements of blood (BAC), breath (BrAC) and urine alcohol concentration (UAC) were performed.
Analyses revealed a significant difference (P<0.0001) between the mean alcohol levels of the Outox and the placebo drinking sessions. The overall mean BAC difference was 0.077 g/l (BAC 0.748 g/l without vs 0.671 g/l with Outox), equivalent to 10.3%. The mean BrAC difference was 0.045 mg/l (BrAC 0.314 mg/l without vs 0.269 mg/l with Outox), equivalent to 14.3%. Differences were lower for women than for men. A significant difference between the alcohol elimination rates (beta 60) was not found.
The results show that the soft drink Outox may decrease the alcohol concentration by about 10%. However, BAC and BrAC differences are rather a consequence of slower gastric absorption of alcohol, because Outox does not increase the alcohol elimination rate. Our study demonstrates that the claim of Outox or other fructose drinks to work as a 'soberade' cannot be proven from a scientific point of view. It should be the task of physicians to warn potential consumers, especially in connection with drinking and driving.
Wiener klinische Wochenschrift 01/2007; 119(3-4):104-11. · 0.81 Impact Factor
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ABSTRACT: In avalanche accidents, the significance of major trauma as a cause of morbidity and mortality is controversial. The aim of this retrospective study is to determine the severity and pattern of injury in avalanche victims admitted to the University Hospital of Innsbruck between 1996 and 2005. A total of 49 significant injuries were found in 105 avalanche victims; the most frequent were of the extremities (n = 20), the chest (n = 18), and the spine (n = 7). In contrast, cerebral (n = 2), abdominal visceral (n = 1), and pelvic trauma (n = 1) were rare. The severity of injury was minor or moderate in most patients, with only 9 (8.6%) being severely or critically injured. Of 105 (34.3%) avalanche victims, 36 died. Autopsy was performed in 30 of 36 nonsurvivors. The cause of death in the remaining 6 victims was concluded from clinical, radiological, and electrophysiological findings. Trauma was responsible for deaths of only 2 avalanche victims (5.6%); both had cervical spine fractures with dislocation leading to death. One death was due to hypothermia, whereas the remaining 33 fatalities (91.7%) were due to asphyxia. The incidence of life-threatening or lethal trauma was well below 10%. Asphyxia is by far the most important reason for death. Deaths from trauma were solely due to isolated cervical injuries, demonstrating that the cervical spine may be a region at particular risk in avalanche victims.
High Altitude Medicine & Biology 01/2007; 8(1):56-61. · 1.77 Impact Factor
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ABSTRACT: To establish the extent to which participants in maintenance treatment programmes (methadone and sublingual buprenorphine) used opioids, benzodiazepines, ethanol, cocaine and amphetamines, and to define the pattern of such use over time. Design: A retrospective analysis of data of 42,610 analyses from urinalysis screening. Setting: Outpatient drug treatment centre, Department of Psychiatry at Innsbruck Medical University, offering maintenance treatment and detoxification programmes in Tyrol, Austria. Measurements: Enzyme-multiplied immunoassay and gas chromatography-mass spectrometry. Results: Urine samples from 23.4% (N = 4998) of those in the methadone treatment group and 16.5% (N = 1110) in the sublingual buprenorphine group tested positive for consumption of additional drugs (p < 0.001). The most frequently detected drugs were benzodiazepines (63% of all methadone, and 40% of all sublingual buprenorphine positive samples; (p < 0.001)) and opioids (26% of all methadone, and 21% of all sublingual buprenorphine positive samples; (p < 0.001)). In both of the treatment programmes morphine abuse (63%) was higher than heroin (7%). There was a significant decrease of benzodiazepine abuse in the study period (2000- 2003) both among clients receiving methadone (p < 0.001) and those receiving sublingual buprenorphine (p = 0.006). Benzodiazepine (Spearman rank correlation coefficient r = 0.281, p < 0.001), cocaine (r = 0.057, p = 0.007), ethanol (r = 0.073, p= 0.028) and morphine (r = -0.179, p < 0.001) abuse were associated with age in sublingual buprenorphine treated patients. Methadone clients showed a lifetime relation for cocaine (r = -0.032, p =0.007), ethanol (Spearman corr. coeff. r = 0.118, p < 0.001), morphine (r = -0.107, p < 0.001) and dihydrocodeine abuse (r = 0.093, p < 0.001). Discussion: The present data indicate that nonprescribed drug use remains a persistent problem for patients in maintenance treatment. Substances misused are mainly opioids and benzodiazepines. Non-prescribed morphine has replaced heroin.
Letters in Drug Design & Discovery 11/2006; 3(10):731-740. · 0.87 Impact Factor
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ABSTRACT: The potential of the combined use of ESI-QqTOF-MS and ESI-QqTOF-MS/MS with mass-spectral library search for the identification of therapeutic and illicit drugs has been evaluated. Reserpine was used for standardizing experimental conditions and for characterization of the performance of the applied mass spectrometric system. Experiments revealed that because of the mass accuracy, the stability of calibration, and the reproducibility of fragmentation, the QqTOF mass spectrometer is an appropriate platform for establishment of a tandem-mass-spectral library. Three-hundred and nineteen substances were used as reference samples to build the spectral library. For each reference compound, product-ion spectra were acquired at ten different collision-energy values between 5 eV and 50 eV. For identification of unknown compounds, a library search algorithm was developed. The closeness of matching between a measured product-ion spectrum and a spectrum stored in the library was characterized by a value called "match probability", which took into account the number of matched fragment ions, the number of fragment ions observed in the two spectra, and the sum of the intensity differences calculated for matching fragments. A large value for the match probability indicated a close match between the measured and the reference spectrum. A unique feature of the library search algorithm-an implemented spectral purification option-enables characterization of multi-contributor fragment-ion spectra. With the aid of this software feature, substances comprising only 1.0% of the total amount of binary mixtures were unequivocally assigned, in addition to the isobaric main contributors. The spectral library was successfully applied to the characterization of 39 forensic casework samples.
Analytical and Bioanalytical Chemistry 10/2006; 386(1):69-82. · 3.78 Impact Factor
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ABSTRACT: 1611 patients were included in this investigation. 16.7% of the patients were involved in traffic accidents, 38.2% were injured by a sudden fall, 3.5% were involved in an act of violence, 22.8% were injured by a sports related accident and 18.9% were hurt within a work-related accident. 19.5% of the patients tested positive for alcohol, 5.2% tested positive for benzodiazepines and 1.4% tested positive for both substances. Blood samples were positive for alcohol in 27% males and 7.7% females and for benzodiazepines in 6.3% males and in 3.5% females. The mean blood alcohol concentration (BAC) as well as the mean benzodiazepine plasma level were higher in patients injured in violent accidents compared to the other injury groups. This study provides epidemiologic information about the relationship between specific kinds of accidents and alcohol and/or benzodiazepine use in a large probability sample of emergency room patients. We found a high number of patients using alcohol, and a lower but still relavant number of benzodiazepine users in this large and unselected traumatology ER sample. This study adds evidence to the existing literature about the co-occurance of alcohol and/or benzodiazepine consumption and accident-related injuries.
Human Psychopharmacology Clinical and Experimental 01/2006; 20(8):583-9. · 2.48 Impact Factor
