Ilkka Ojanperä

University of Helsinki, Helsinki, Southern Finland Province, Finland

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Publications (116)279.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pregabalin is a medicinal drug used mainly for the treatment of epilepsy and neuropathic pain. It has been shown to possess an abuse potential and in recent years some reports of illegal use have been published. In order to further evaluate the extent and nature of pregabalin abuse, serum pregabalin levels of drivers apprehended for driving under the influence of drugs (DUID) in Finland in 2012 were assessed. The samples were analysed by an LC–MS/MS system and the results were evaluated in relation to the typical therapeutic range of pregabalin as well as the age and gender of the driver. Pregabalin was detected in 206 samples in the study period. The median (range) serum concentration was 6.2 (0.68–111.6) mg/L. In nearly 50% of the cases the serum concentration was above the typical therapeutic range. In most of the cases the driver had also taken other drugs besides pregabalin, the mean number of concomitantly taken drugs being four. Our data indicate that pregabalin is being used at high doses, probably for recreational purposes. The vast majority of the drivers positive for pregabalin in our study material had used pregabalin as a part of a spectrum of psycho-active drugs and thus qualified as probable drug abusers. In these cases pregabalin probably contributed to their driving impairment but to what extent remained unclear in this study.
    Forensic Science International 07/2014; 243:112-116. · 2.31 Impact Factor
  • Mira Sundström, Anna Pelander, Ilkka Ojanperä
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    ABSTRACT: Immunoassay is currently the most common approach for urine drug screening. However, the continuous emergence of new psychoactive substances (NPS) and their low urinary concentrations have challenged the scope and sensitivity of immunoassays. Consequently, specialized toxicology laboratories rely more and more on mass spectrometry (MS) based techniques. Ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOF-MS) is an especially attractive technique for comprehensive drug screening. The objective was to compare the performances of immunoassay and UHPLC-HR-TOF-MS in terms of scope, flexibility, sensitivity, and reliability of substance identification. A total of 279 post-mortem urine samples were analyzed using a method representative of each technique. The immunoassay method was an Emit II Plus enzyme immunoassay for the following drug groups: amphetamines, benzodiazepines, buprenorphine, cannabis, and opiates. The UHPLC-HR-TOF-MS method was a recently published method covering hundreds of drugs: conventional drugs of abuse, abused prescription drugs, and NPS of various classes. UHPLC-HR-TOF-MS produced a lower number of false positive (FP) results for the drug groups covered by immunoassay. Many of the false negative (FN, n = 40) and FP (n = 22) immunoassay results were obviously due to the higher cut-off concentrations and interfering matrix, respectively. Moreover, the wider scope of UHPLC-HR-TOF-MS allowed detection of NPS and prescription drugs. UHPLC-HR-TOF-MS gave FP results related to a few particular substances. The future option of adjusting all compound-specific reporting parameters individually would allow the method's sensitivity and specificity to be fully exploited. Copyright © 2014 John Wiley & Sons, Ltd.
    Drug Testing and Analysis 06/2014; · 3.17 Impact Factor
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    ABSTRACT: The β-keto amphetamine (cathinone, β-KA) designer drugs such as mephedrone (4-methylmethcathinone, 4-MMC) show a large degree of structural similarity to amphetamines like methamphetamine (METH). However, little is currently known about whether these substances also share the potential neurotoxic properties of their non-keto amphetamine counterparts, or what mechanisms could be involved. Here, we evaluate the cytotoxicity of β-KAs in SH-SY5Y cells using lactate dehydrogenase (LDH) assays, assess the redox potential of a range of β-KAs and non-keto amphetamines using the sensitive redox indicator 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) and explore the effect of 4-MMC on the formation of protein adducts using ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) and on the mitochondrial respiratory chain using high resolution respirometry. We show that treatment with β-KAs increases LDH release. Further, we demonstrate that even under physiological pH, β-KAs are effective and selective-as compared to their non-keto analogues-reductants in the presence of electron acceptors. Increased pH (range 7.6-8.0) greatly enhanced the reactivity up to six-fold. We found no evidence of protein adduct formation, suggesting the reactivity is due to direct electron transfer by the β-KAs. Finally, we show that 4-MMC and METH produce dissimilar effects on the respiratory chain. Our results indicate that β-KAs such as 4-MMC possess cytotoxic properties in vitro. Furthermore, in the presence of an electron-accepting redox partner, the ketone moiety of β-KAs is vital for pH-dependent redox reactivity. Further work is needed to establish the importance of β-KA redox properties and its potential toxicological importance in vivo.
    Toxicological sciences : an official journal of the Society of Toxicology. 06/2014;
  • M Sundström, A W Jones, I Ojanperä
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    ABSTRACT: Use and abuse of alcohol are common findings when unnatural deaths are investigated as evidenced by high blood- and urine- alcohol concentrations (BAC and UAC) at autopsy. Because ethanol is metabolized in the liver until the time of death, the autopsy BAC or UAC might be negative even though the deceased had consumed alcohol in the immediate ante-mortem period. Analysis of the non-oxidative metabolite of ethanol [ethyl glucuronide (EtG)] offers a more sensitive test of recent drinking. In this paper, we determined the concentrations of ethanol and EtG in urine samples from 972 consecutive forensic autopsies. In 425 cases (44%) both EtG and ethanol were positive, which supports ante-mortem drinking. In 342 cases (35%), both EtG and ethanol was negative, which speaks against any consumption of alcohol just before death. In 181cases, ethanol was negative in urine (<0.2g/kg), whereas EtG was positive (>0.5mg/L), which points towards ingestion of alcohol some time before death. In these cases, mean and median concentrations of EtG were 53.2mg/L and 23.7mg/L, respectively, although there was no mention of alcohol on 131 of the death certificates. Alcohol was mentioned on death certificates as an underlying or immediate cause of death or a contributing factor in 435 (45%) cases, which rose to 566 (58%) cases when positive EtG results were included. This article demonstrates the usefulness of EtG analysis in routine post-mortem toxicology when ante-mortem drinking and alcohol-related deaths are investigated.
    Forensic science international. 06/2014; 241C:178-182.
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    ABSTRACT: Pregabalin (PRG) and gabapentin (GBP) are used in the treatment of neuropathic pain and epilepsy, and PRG also in generalized anxiety disorder. There is increasing evidence that PRG possesses considerable abuse potential. PRG may have a higher addiction potential than GBP due to its rapid absorption and faster onset of action. Our objective is to estimate the proportion of all PRG- and GBP-related fatalities attributable to PRG and GBP abuse. We investigated all medico-legal death cases in Finland in which PRG or GBP was found in postmortem toxicology during 2010-2011. PRG was found in 316 cases and GBP in 43 cases. Drug abuse was associated with 48.1% of the PRG and 18.6% of the GBP findings. PRG poisoning accounted for 10.1% of all PRG cases and GBP poisoning for 4.7% of all GBP cases. In the drug abuser cases, PRG poisoning represented 19.1%, and GBP poisoning 12.5%. The median blood concentration of PRG was 15mg/L in the abuser group and 5.8mg/L in the other cases. For GBP, these concentrations were 12mg/L and 8.3mg/L, respectively. In the PRG abuser group, 91.4% of cases showed concomitant opioid use, while in the rest of these cases neither alcohol nor opioids were detected, but other central nervous system acting drugs were found in each abuser case. In the GBP abuser group, 87.5% of cases showed concomitant opioid use. PRG abuse with high doses is increasingly common and can be fatal when combined with opioids.
    Forensic science international. 05/2014; 241C:1-6.
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    ABSTRACT: Hand-held electronic breath-alcohol analyzers are widely used by police authorities in their efforts to detect drunken drivers and to improve road-traffic safety. Over a three month period, the results of roadside breath-alcohol tests of drivers apprehended in Finland were compared with venous blood alcohol concentration (BAC). The mean (median) time between sampling blood and breath was 0.71h (0.58h) with a range from 0 to 6h. Some hand-held instruments gave results as the concentration of alcohol in breath and were converted into BAC assuming a blood-breath alcohol ratio (BBR) of 2260. The mean venous BAC (1.82g/kg) in traffic offenders was higher than the result predicted by the hand-held breath analyzers (1.72g/kg). In 1875 roadside tests, the relationship between venous BAC (x) and BrAC (y) was defined by the regression equation y=0.18+0.85x. The coefficients show both a constant bias (y-intercept 0.18g/kg) and a proportional bias (slope=0.85). The residual standard deviation (SD), an indicator of random variation, was ±0.40g/kg. After BAC results were corrected for the time elapsed between sampling blood and breath, the y-intercept decreased to 0.10g/kg and 0.004g/kg, respectively, when low (0.1g/kg/h) and high (0.25g/kg/h) rates of alcohol elimination were used. The proportional bias of 0.85 shows that the breath-alcohol test result reads lower than the actual BAC by 15% on average. This suggests that the BBR of 2260 used for calibration should be increased by about 15% to give closer agreement between BAC and BrAC. Because of the large random variation (SD±0.40g/kg), there is considerable uncertainty if and when results from the roadside screening test are used to estimate venous BAC. The roadside breath-alcohol screening instruments worked well for the purpose of selecting drivers above the statutory limit of 0.50g/kg.
    Forensic science international 03/2014; 239C:57-61. · 2.10 Impact Factor
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    ABSTRACT: Sixty-one different psychoactive substances were quantified by liquid chromatography-chemiluminescence nitrogen detection (LC-CLND) in 177 samples, using a single secondary standard (caffeine), in a trial concerning the quantitative purity assessment of drug-related material seized by the police in 2011-2012 and customs in 2011-2013 in Finland. The substances found were predominantly substituted phenethylamines, cathinones, tryptamines and synthetic cannabinoids, which were identified by appropriate methods prior to submitting the samples for quantification by LC-CLND. The equimolarity and expanded uncertainty of measurement by LC-CLND were on average 95% and 13%, respectively, based on 16 different substances. The median (mean) purity of stimulant/hallucinogenic drug samples seized at the border was 92.9% (87.6%) and in the street 82.0% (64.5%). The corresponding figures for powdery synthetic cannabinoid samples seized at the border and in the street were 99.0% (96.8%) and 90.0% (92.2%), respectively. There was generally only one active drug to be quantified in each sample. Seized herbal samples contained 0.15-9.2% of between one and three components. LC-CLND was found to be suitable for quantification of the nitrogen-containing drugs encountered in the study, showing sufficient N-equimolarity for both stimulant/hallucinogenic drugs and synthetic cannabinoids. The technique possesses great potential as a standard technique in forensic laboratories.
    Forensic science international 02/2014; 237C:119-125. · 2.10 Impact Factor
  • M. Sundström, A. Pelander, I. Ojanperä
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    ABSTRACT: Introduction Immunoassay screening tests are widely used in clinical and forensic toxicology. However, the emergence of new psychoactive substances (NPS) has challenged the scope and sensitivity of these methods. Consequently, specialized analytical toxicology laboratories are today relying more and more on mass spectrometry based techniques. Ultra-high performance liquid chromatography/ high resolution time-of-flight mass spectrometry (UHPLCHR- TOFMS) is an especially attractive technique for comprehensive drug screening in terms of scope, sensitivity and reliability of identification. The objective of the present study was to compare the performance of these two analytical approaches in urine screening for conventional drugs of abuse and NPS. Methods A total of 279 post-mortem urine samples were analyzed by both an immunoassay (Emit II Plus) and an UHPLC-HRTOFMS screening method. Sample preparation prior to immunoassay was only a centrifugation step, while UHPLC-HR-TOFMS analysis was preceded by solid-phase extraction, including both acidic/neutral and basic fractions. The instrumentation consisted of a Dionex Ultimate 3000 series UHPLC coupled with a Bruker Daltonics maXis Impact HR-TOFMS. Simultaneous acquisition of MS and broad band collision induced fragmentation (bbCID) data was applied. Compound identification was based on post-targeted database search with preset reporting criteria for mass accuracy, isotopic pattern match, retention time, and abundance criteria for qualifier ions. The immunoassay drug panel included amphetamines, benzodiazepines, buprenorphine, cocaine, opiates, and cannabis. The UHPLC-HR-TOFMS method comprised conventional drugs of abuse, various classes of NPS, such as synthetic cannabinoids and cathinones, and commonly abused prescription drugs such as tramadol and pregabalin. Results The UHPLC-HR-TOFMS and immunoassay results were compared with quantitative confirmation analyses by established GC-MS and LC-MS/MS methods. The UHPLC-HR-TOFMS results for amphetamines (n=11), buprenorphine (n=27), cannabis (n=28), opiates (n=31), and benzodiazepines (n=99) showed excellent correlation with confirmation analyses, whereas many false negative immunoassay results existed obviously due to high cut-off concentrations and interfering matrix. Moreover, the wider scope of UHPLC-HR-TOFMS method allowed detection of NPS (n=4) and prescription drugs (n=88). A total of 22 false positive (FP) results were produced by immunoassay. For example, the immunoassay gave ten FP buprenorphine results, for which both UHPLC-HRTOFMS and quantification analyses were negative. The UHPLC-HRTOFMS FP results were mainly due to the interference from early eluting endogenous compounds or due to the ion source cleavage of reduced oxycodone resulting in a structure corresponding to codeine. UHPLC-HR-TOFMS revealed additional low-concentration drug findings. The correspondence between symmetric peaks of precursor and qualifier ions supported these results, which were, however, undetectable by confirmation methods. Simultaneous detection of parent compound and metabolites enhances the reliability of compound identification. Conclusions Due to the superior results from UHPLC-HR-TOFMS screening, this method has replaced immunoassay in the authors’ laboratory. The possibility to collect both MS and bbCID data simultaneously in a single run increases the reliability of identification and reduces the need for confirmation analyses. However, the data processing parameters of the software should provide more options for individual reporting criteria, which would notably reduce the number of FP results without compromising sensitivity.
    Toxicologie Analytique et Clinique. 01/2014; 26(2):S18.
  • M. Sundström, A.W. Jones, I. Ojanperä
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    ABSTRACT: Use and abuse of alcohol are common findings when unnatural deaths are investigated as evidenced by high blood- and urine- alcohol concentrations (BAC and UAC) at autopsy. Because ethanol is metabolized in the liver until the time of death, the autopsy BAC or UAC might be negative even though the deceased had consumed alcohol in the immediate ante-mortem period. Analysis of the non-oxidative metabolite of ethanol [ethyl glucuronide (EtG)] offers a more sensitive test of recent drinking. In this paper, we determined the concentrations of ethanol and EtG in urine samples from 972 consecutive forensic autopsies. In 425 cases (44%) both EtG and ethanol were positive, which supports ante-mortem drinking. In 342 cases (35%), both EtG and ethanol was negative, which speaks against any consumption of alcohol just before death. In 181cases, ethanol was negative in urine (<0.2 g/kg), whereas EtG was positive (>0.5 mg/L), which points towards ingestion of alcohol some time before death. In these cases, mean and median concentrations of EtG were 53.2 mg/L and 23.7 mg/L, respectively, although there was no mention of alcohol on 131 of the death certificates. Alcohol was mentioned on death certificates as an underlying or immediate cause of death or a contributing factor in 435 (45%) cases, which rose to 566 (58%) cases when positive EtG results were included. This article demonstrates the usefulness of EtG analysis in routine post-mortem toxicology when ante-mortem drinking and alcohol-related deaths are investigated.
    Forensic Science International. 01/2014; 241:178–182.
  • J. Viinamäki, I. Ojanperä
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    ABSTRACT: Introduction Mass spectrometric (MS) methods are today widely used in analytical toxicology, but in comprehensive quantitative drug screening it is laborious to maintain quantitative calibration and use of historic calibration is not feasible. In non-MS gas chromatographic (GC) and liquid chromatographic (LC) methods, historic calibration is widely used. However, GC is not amenable to analysis of current polar drugs and traditional LC-UV methods do not have high enough identification power to meet the requirements of screening. Ultra-performance LC (UPLC) with two consecutive detectors appears to possess high potential for simultaneous multi-component screening and quantification. In this study, a comprehensive quantitative screening method for 170 basic drugs in blood samples was developed and validated using UPLC coupled with photodiode array (PDA) and corona charged aerosol detector (CAD). Methods Blood samples were extracted with organic solvent (ethyl acetate: butyl acetate, 25:75) in basic conditions. After extraction, the organic solvent was evaporated to dryness and samples were reconstituted with the UPLC mobile phase. Dibenzepine was used as an internal standard. Chromatographic separation was performed at 60 °C using a HSS C18 column (150 mm × 2,1 mm, particle size 1,8 μm), and the mobile phase consisted of 0.1% trifluoroacetic acid and methanol. After a three minute isocratic phase, a linear gradient from 5% to 95% methanol in 15 minutes followed. The flow rate was 0.4 mL/min. UV spectra were collected in the range of 210–400 nm, and wavelength of 230 nm was used for quantification. Substance identification was based on the UV spectrum, retention times on both detectors, and the response ratio of CAD and PDA at wavelength 230 nm. Calibration was carried out using a single calibration point at the vicinity of the upper limit of therapeutic range of each drug. Individual calibration curves were created for both detectors and the average result was used for quantification. Results The retention times were found be very stable, the relative standard deviation of retention times being <0.03% intraday and <0.3% interday. In order to simplify data processing and interpretation of the reports, the analytes were divided into five data processing methods, each containing every fifth analyte based the retention time. This approach provided a maximum of five candidates for each peak, thus simplifying manual interpretation even with more complicated samples. Linearity of one-point calibration was found to be acceptable within the therapeutic and toxic ranges of the drugs of interest, with linear ranges generally being 0.05–5,0 mg/L or 0.1–5,0 mg/L. Calibration was found to be stable over one month, the bias between old and new calibration being <15%. Conclusion The developed method allows the detection and quantification of 170 basic drugs in therapeutic and toxic concentrations in a single run. Due to the stability of calibration and good linearity, historic one-point calibration can be utilized. Adding the CAD detector with universal response after the PDA detector increases the reliability of both identification and quantification. In addition, drugs with poor UV absorption can be detected and quantitated. This method provides a tool for comprehensive quantitative screening for ordinary basic drugs in blood and leaves LC-MS target analysis to be applied to low-dose compounds.
    Toxicologie Analytique et Clinique. 01/2014; 26(2):S18–S19.
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    ABSTRACT: Differentiation of insulin analogues is required in forensic and clinical toxicology as well as in sports doping control. Immunoassay results provide only weak evidence for exogenous administration of insulin, as concentrations cannot be reliably interpreted and specific information on the insulin species remains unknown. In post-mortem blood, insulin degrades rapidly. In this study, improved methodology consisting of precipitation of proteins, immunoaffinity purification and liquid chromatography coupled to high resolution/high accuracy mass spectrometry were applied to post-mortem vitreous humour. Ten successive cases with a post-mortem interval from four to ten days were investigated for insulin analogues. The cause of death in these cases was connected with diabetes and its complications, as well as with chronic cardiovascular disease, alcoholism and cancer. In all cases, the manner of death was natural (disease). Insulin was positively detected in post-mortem vitreous humour in three cases out of ten by mass spectrometry. In two cases, the method revealed the long-acting insulin glargine (Lantus) metabolite M2 (DesB31-32 Lantus), and human insulin was detected in one case. The findings were in agreement with the documented history of insulin medication. No other obvious reason could be found for the failure of detecting insulins in the other cases than insulin degradation during the lengthy post-mortem interval. Vitreous humour is still a most prospective specimen for detection of insulin analogues post-mortem.
    Forensic science international 12/2013; 233(1-3):328-32. · 2.10 Impact Factor
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    ABSTRACT: Buprenorphine (BPN) medication for opioid maintenance treatment in Finland consists predominantly of buprenorphine-naloxone (BNX). Both BPN and BNX are associated with diversion, abuse and non-medically supervised use worldwide. Our purpose was to estimate the proportion of BNX to all BPN-related fatalities. The material consisted of 225 deceased drug abusers in Finland from January 2010 to June 2011 with a positive BPN and/or norbuprenorphine (NOR) and/or naloxone (NX) finding in urine. The data were divided into three groups based on the urine NX and BPN concentrations. The "Parenteral BNX" group (>100μg/l NX) was presumed to consist of injecting or snorting BNX abusers and the "Parenteral BPN" group (>50μg/l BPN, 0μg/l NX) of injecting or snorting BPN abusers, while the "Other BNX or BPN" group (≤100μg/l NX, or ≤50μg/l BPN combined with 0μg/l NX) was presumed to consist of mainly sublingual BNX or BPN users. In 12.4% of cases the NX urine concentration was higher than the threshold 100μg/l. In fatal BPN poisonings, the proportion of parenteral BNX was 28.4%. In the "Parenteral BNX", "Parenteral BPN" and "Other BNX or BPN" groups, the proportion of fatal BPN poisonings was 67.9, 31.0 and 22.6%, respectively. BNX abuse can be fatal. Among the 225 BPN-related fatalities, parenteral abuse of BNX was shown to be common (12.4%) and BNX poisoning was the underlying cause of death in 8.4%. Parenteral BNX caused fatal BPN poisoning proportionally more often than parenteral BPN.
    Forensic science international 10/2013; 232(1-3):11-5. · 2.10 Impact Factor
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    ABSTRACT: The continuing emergence of designer drugs imposes high demands on the scope and sensitivity of toxicological drug screening procedures. An ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) method was developed for screening and simultaneous confirmation of both designer drugs and other drugs of abuse in urine samples in a single run. The method covered selected synthetic cannabinoids and cathinones, amphetamines, natural cannabinoids, opioids, cocaine and other important drugs of abuse, together with their main urinary metabolites. The database consisted of 277 compounds with molecular formula and exact monoisotopic mass; retention time was included for 192 compounds, and primary and secondary qualifier ion exact mass for 191 and 95 compounds, respectively. Following a solid-phase extraction, separation was performed by UHPLC and mass analysis by HR-TOFMS. MS, and broad-band collision-induced dissociation data were acquired at m/z range 50-700. Compound identification was based on a reverse database search with acceptance criteria for retention time, precursor ion mass accuracy, isotopic pattern and abundance of qualifier ions. Mass resolving power in spiked urine samples was on average FWHM 23,500 and mass accuracy 0.3 mDa. The mean and median cut-off concentrations determined for 75 compounds were 4.2 and 1 ng/mL, respectively. The range of cut-off concentrations for synthetic cannabinoids was 0.2-60 ng/mL and for cathinones 0.7-15 ng/mL. The method proved to combine high sensitivity and a wide scope in a manner not previously reported in drugs of abuse screening. The method's feasibility was demonstrated with 50 authentic urine samples.
    Analytical and Bioanalytical Chemistry 08/2013; · 3.66 Impact Factor
  • Terhi Launiainen, Ilkka Ojanperä
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    ABSTRACT: Therapeutic drug concentrations measured in plasma are of limited value as reference intervals for interpretation in post-mortem (PM) toxicology. In this study, drug concentration distributions were studied in PM femoral venous blood from 57 903 Finnish autopsy cases representing all causes of death during an 11-year period. Cause-of-death information was obtained from death certificates issued by forensic pathologists. Median, mean, and upper percentile (90th, 95th, 97.5th) concentrations were calculated for 129 drugs. To illustrate how PM median concentrations relate to established therapeutic ranges in plasma, a PM blood/plasma relationship was calculated for each drug. Males represented 75% of the subjects and showed a lower median age (55 yrs) than females (59 yrs). In 43% of these cases, blood alcohol concentration was higher than 0.2‰, and the median was 1.8‰. Sixty-one (47%) of the 129 drugs showed a PM blood/plasma relationship of 1. For 22 drugs (17%), the relationship was <1, and for 46 drugs (35%), the relationship was >1. No marked correlation was found between the PM blood/plasma relationship and the volume of distribution (Vd ). For 36 drugs, more than 10% of cases were fatal poisonings attributed to this drug as the main finding. These drug concentration distributions based on a large database provide a helpful reference not only to forensic toxicologists and pathologists but also to clinical pharmacologists in charge of interpreting drug concentrations in PM cases. © 2013 The Authors. Drug Testing and Analysis published by John Wiley & Sons, Ltd.
    Drug Testing and Analysis 07/2013; · 3.17 Impact Factor
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    ABSTRACT: Human phase I metabolism of four designer drugs, 2-desoxypipradrol (2-DPMP), 3,4-dimethylmethcathinone (3,4-DMMC), α-pyrrolidinovalerophenone (α-PVP), and methiopropamine (MPA), was studied using in silico and in vitro metabolite prediction. The metabolites were identified in drug abusers' urine samples using liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC/Q-TOF/MS). The aim of the study was to evaluate the ability of the in silico and in vitro methods to generate the main urinary metabolites found in vivo. Meteor 14.0.0 software (Lhasa Limited) was used for in silico metabolite prediction, and in vitro metabolites were produced in human liver microsomes (HLMs). 2-DPMP was metabolized by hydroxylation, dehydrogenation, and oxidation, resulting in six phase I metabolites. Six metabolites were identified for 3,4-DMMC formed via N-demethylation, reduction, hydroxylation, and oxidation reactions. α-PVP was found to undergo reduction, hydroxylation, dehydrogenation, and oxidation reactions, as well as degradation of the pyrrolidine ring, and seven phase I metabolites were identified. For MPA, the nor-MPA metabolite was detected. Meteor software predicted the main human urinary phase I metabolites of 3,4-DMMC, α-PVP, and MPA and two of the four main metabolites of 2-DPMP. It assisted in the identification of the previously unreported metabolic reactions for α-PVP. Eight of the 12 most abundant in vivo phase I metabolites were detected in the in vitro HLM experiments. In vitro tests serve as material for exploitation of in silico data when an authentic urine sample is not available. In silico and in vitro designer drug metabolism studies with LC/Q-TOF/MS produced sufficient metabolic information to support identification of the parent compound in vivo.
    Analytical and Bioanalytical Chemistry 06/2013; · 3.66 Impact Factor
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    ABSTRACT: Fatal alcohol and drug poisonings in Finland during the years 2004-2009 were studied. Cases were divided into those that occurred outside the hospitals (the majority of cases) and those that occurred within the hospitals (the minority of cases). Differences and similarities between the two groups were analysed. The postmortem toxicological investigation of all sudden and unexpected deaths in Finland is centralised at the Department of Forensic Medicine, University of Helsinki. We examined each fatal poisoning separately and verified the cause and place of death as well as the age and sex of the deceased. Fatal poisonings, including suicides, have remained unchanged for many years from the same high level, that is, about 1200 cases annually (22/100,000 inhabitants). The number of patients dying in hospitals due to poisoning has also remained stable (55-70 patients/year). However, the toxic agents involved in such poisonings have changed and deaths due to opioids are now being more numerous. The number of fatal unintentional drug poisonings rose significantly from 191 to 341 (3-6/100,000 inhabitants, p < 0.001) during the study years, and the difference between poisonings caused by drugs or alcohol also changed significantly (p < 0.001). Diminishing substantially, the number of all fatal poisonings will be challenging because of the high percentage of suicides. However, a reduction in unintentional drug overdoses, which are presently on the rise, should be possible.
    Human & Experimental Toxicology 06/2013; 32(6):600-5. · 1.31 Impact Factor
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    ABSTRACT: A case of serial killing by poisoning by a 59-year-old practical nurse is discussed. Following a report by an emergency-room doctor of an attempted murder, police performed an investigation into all deaths of patients in the nurse's care. Earlier, a medico-legal cause-of-death investigation had been performed on two of these cadavers, but in the other three cases the death certificate had been issued after a medical investigation only. In two of these latter cases, the body had been cremated, but fixed histological samples taken at medical autopsy were available, while in one case the person had died recently and the body was thereafter exhumed and autopsied. All of the suspected victims were older people who required nursing, and the nurse's course of action was consistent in all cases. In the absence of ordinary post-mortem toxicology samples in the medical cases, extraordinary evidence - paraffin-embedded liver tissue samples originally taken for histology at autopsy - was successfully recovered in two cases and analyzed for drugs. In all five cases, drugs not prescribed to the patient were detected, including digoxin, dixyrazine, citalopram, venlafaxine, and benzodiazepines (diazepam, chlordiazepoxide, temazepam, and oxazepam). The nurse was eventually found guilty of five murders by poisoning, five attempted murders, and three aggravated assaults. The nurse was sentenced to life imprisonment. Copyright © 2013 John Wiley & Sons, Ltd.
    Drug Testing and Analysis 04/2013; · 3.17 Impact Factor
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    ABSTRACT: In spite of the benefits of buprenorphine-naloxone co-formulation (BNX) in opioid maintenance treatment, the naloxone component has not prevented parenteral use of BNX. Current laboratory methods are not sufficient to differentiate between therapeutic and illicit use of buprenorphine, and little is known about urine naloxone concentrations. Measurement of urine naloxone, together with buprenorphine and norbuprenorphine, might help to determine the naloxone source and administration route. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for this purpose. Naloxone, buprenorphine, and norbuprenorphine total concentrations were measured in urine samples from opioid-dependent patients before and during stable and unstable phases of maintenance treatment with BNX. The limit of quantification in urine was 1.0 µg/L for naloxone, buprenorphine and norbuprenorphine. Before treatment, all samples contained buprenorphine but the median naloxone concentration was 0 µg/L. During the maintenance treatment with BNX all urine samples were positive for naloxone, buprenorphine and norbuprenorphine. The naloxone concentration at a stable phase of treatment (median 60 µg/L, range 5-200 µg/L) was not different from the naloxone concentration at an unstable phase (70 µg/L, 10-1700 µg/L). Applying an upper limit of 200 µg/L to the sample, the median naloxone/buprenorphine ratio was higher in the high than in the low naloxone concentration group (0.9 vs 0.3, respectively). This study suggests that naloxone in urine can act as an indicator of compliance with BNX. Parenteral use of BNX was associated with a high naloxone/buprenorphine ratio. Negative naloxone with positive buprenorphine suggests the use/abuse of buprenorphine alone. Copyright © 2013 John Wiley & Sons, Ltd.
    Drug Testing and Analysis 03/2013; · 3.17 Impact Factor
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    ABSTRACT: Meconium drug testing is a non-invasive method to detect prenatal drug exposure, which can cause severe problems for the infant, indicating the need for follow-up measures to ensure the welfare of the child. Meconium samples for drug testing were collected from 143 infants as part of routine clinical work among addicted mothers. The drug testing findings were combined with medical records including clinical background and follow-up data. The substances screened for included medicinal opioids, 6-monoacetylmorphine (a metabolite of heroin), amphetamines and tetrahydrocannabinolic acid. At least one of the 13 target drugs was detected in 57 (40%) meconium samples. In 21 cases, the findings were unexpected on the basis of clinical data or denied by the mother. Medicinal opioids, especially the opioid substitution treatment drugs buprenorphine and methadone, comprised the majority of the findings of both admitted and unexpected drug misuse. Meconium drug testing methods should target not just traditional illicit drugs but also prescription drugs with misuse potential. Copyright © 2013 John Wiley & Sons, Ltd.
    Drug Testing and Analysis 02/2013; · 3.17 Impact Factor
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    ABSTRACT: The aim of this study was to assess the incidence of the use of desoxypipradrol (2-DPMP) among drivers apprehended on suspicion of driving under the influence of drugs (DUID) and the prevalence of the drug in post-mortem cases in Finland. Serum samples from drivers apprehended on suspicion of DUID and blood samples from post-mortem cases in Finland between October 2010 and May 2012 were analysed for the presence of desoxypipradrol. All samples were analysed for desoxypipradrol by mass spectrometric methods following comprehensive drug screening. Psychomotor performance of subjects was assessed by a clinician. There were 106 positive desoxypipradrol samples from apprehended drivers (1.7% of all confirmed DUID cases) in the study period. In most cases amphetamine and/or benzodiazepines were also present. The median (range) desoxypipradrol concentration was 0.073mg/L (0.006-0.890mg/L). The presence of other psychoactive drugs confounded assessment of the effect of desoxypipradrol on psychomotor performance except for one case in which it was the only drug present at pharmacologically active levels. Desoxypipradrol was found in 5 autopsy cases (0.05% of the investigated cases) and thought to contribute to death in two of these. Even though there are few data available on the pharmacology of desoxypipradrol, based on our findings, and the growing number of users, it is reasonable to assume that desoxypipradrol - a long-acting psychostimulant with dangerous side effects has an increasing detrimental impact on traffic safety in Finland. However, it was only rarely found to be the cause of death in post-mortem cases.
    Forensic science international 01/2013; · 2.10 Impact Factor

Publication Stats

1k Citations
279.54 Total Impact Points

Institutions

  • 1987–2014
    • University of Helsinki
      • • Department of Chemistry
      • • Laboratory of Analytical Chemistry
      Helsinki, Southern Finland Province, Finland
  • 1987–2013
    • Helsinki University Central Hospital
      Helsinki, Southern Finland Province, Finland
  • 2011
    • Deutsche Sporthochschule Köln
      • Institut für Trainingswissenschaft und Sportinformatik
      Köln, North Rhine-Westphalia, Germany
  • 2004–2006
    • Kuopio University Hospital
      • Department of Anaesthesiology
      Kuopio, Province of Eastern Finland, Finland
  • 2000
    • Finnish Environment Institute
      Helsinki, Southern Finland Province, Finland