Ilkka Ojanperä

University of Helsinki, Helsinki, Southern Finland Province, Finland

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Publications (107)252.57 Total impact

  • [show abstract] [hide abstract]
    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
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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 0.71 h (0.58 h) with a range from 0-6 h. 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 (1.82 g/kg) in traffic offenders was higher than the result predicted by the hand-held breath analyzers (1.72 g/kg). In 1875 roadside tests, the relationship between venous BAC (x) and BrAC (y) was defined by the regression equation y = 0.18 + 0.85 x. The coefficients show both a constant bias (y-intercept 0.18 g/kg) and a proportional bias (slope = 0.85). The residual standard deviation (SD), an indicator of random variation, was ±0.40 g/kg. After BAC results were corrected for the time elapsed between sampling blood and breath, the y-intercept decreased to 0.10 g/kg and 0.004 g/kg, respectively, when low (0.1 g/kg/h) and high (0.25 g/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 ± 0.40 g/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 0.50 g/kg.
    Forensic Science International. 01/2014;
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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
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    ABSTRACT: INTRODUCTION/AIMS: The use of cathinone-derivative designer drugs methylone and mephedrone has increased rapidly in recent years. Our aim was to investigate the possible long-term effects of these drugs on a range of behavioral tests in mice. Further, we investigated the long-term effects of these drugs on brain neurochemistry in both rats and mice. METHODS: We treated animals with a binge-like regimen of methylone or mephedrone (30mg/kg, twice daily for 4days) and, starting 2weeks later, we performed behavioral tests of memory, anxiety and depression and measured brain levels of dopamine (DA), serotonin (5-HT), their metabolites and norepinephrine (NE). 5-HT and DA transporter (5-HTT, DAT) levels were also measured in rats by [(3)H]paroxetine and [(3)H]mazindol binding. RESULTS: Mephedrone reduced working memory performance in the T-maze spontaneous alternation task but did not affect neurotransmitter levels aside from a 22% decrease in striatal homovanillic acid (HVA) levels in mice. Methylone had little effect on behaviour or neurotransmitter levels in mice but produced a widespread depletion of 5-HT and 5-HTT levels in rats. CONCLUSIONS: Both methylone and mephedrone appeared to have a long-term effect on either behavioral or biochemical gauges of neurotoxicity in rodents.
    Pharmacology Biochemistry and Behavior 10/2012; · 2.61 Impact Factor
  • Pekka Ostman, Raimo A Ketola, Ilkka Ojanperä
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    ABSTRACT: Product ion spectra obtained with liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) were applied to the identification of seized drug samples from atmospheric pressure matrix-assisted laser desorption/ionization product ion spectra (AP-MALDI-MS/MS spectra). Data acquisition was performed in the information-dependent acquisition (IDA) mode, and the substance identification was based on a spectral library previously created with LC-ESI/MS/MS using protonated molecules as precursor ions. A total of 39 seized drug samples were analyzed with both AP-MALDI and LC-ESI techniques using the same triple-quadrupole instrument (AB Sciex 4000QTRAP). The study shows that ESI-MS/MS spectra can be directly utilized in AP-MALDI-MS/MS measurements as the average fit and purity score percentages with AP-MALDI were 90% and 85%, respectively, being similar to or even better than those obtained with the reference LC/ESI-MS/MS method. This fact enables the possibility to use large ESI spectral libraries, not only to ESI analyses but also to analyses with other ionization techniques which produce protonated molecules as the base peak. The data obtained shows that spectral library search works also for analytical techniques which produce multi-component mass spectra, such as AP-MALDI, unless isobaric compounds are encountered. The spectral library search was successfully applied to rapid identification of confiscated drugs by AP-MALDI-IDA-MS/MS. Copyright © 2012 John Wiley & Sons, Ltd.
    Drug Testing and Analysis 09/2012; · 3.17 Impact Factor
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    ABSTRACT: There is a rising trend of fatal poisonings due to medicinal opioids in several countries. The present study evaluates the drug and alcohol findings as well as the cause and manner of death in opioid-related post-mortem cases in Finland from 2000 to 2008. During this period, fatal poisonings by prescription opioids (buprenorphine, codeine, dextropropoxyphene, fentanyl, methadone, oxycodone, tramadol) increased as a share of all drug poisonings from 9.5% to 32.4%, being 22.3% over the whole period. A detailed study including the most prevalent opioids was carried out for the age group of 14-44 years, which is the most susceptible age for drug abuse in Finland. Poisonings by the weak opioids, codeine and tramadol, were found to be associated with large, often suicidal overdoses resulting in high drug concentrations in blood. Methadone poisonings were associated with accidental overdoses with the drug concentration in blood remaining within a therapeutic range. The manner of death was accidental in 43%, 55% and 94% of cases in codeine, tramadol and methadone poisonings, respectively. The median concentration of codeine and the median codeine/morphine concentration ratio were higher in codeine poisonings (1.4 and 22.5 mg/l, respectively) than in other causes of death (0.09 and 5.9 mg/l, respectively). The median concentrations of tramadol and O-desmethyltramadol were higher in tramadol poisonings (5.3 and 0.8 mg/l, respectively) than in other causes of death (0.6 and 0.2 mg/l, respectively). In methadone poisonings, the median concentration of methadone (0.35 mg/l) was not different from that in other causes of death (0.30 mg/l). Sedative drugs and/or alcohol were very frequently found in fatal poisonings involving these prescription opioids.
    Forensic science international 08/2012; 222(1-3):327-31. · 2.10 Impact Factor
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    ABSTRACT: A method based on in-source collision-induced dissociation (ISCID) liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) and reverse target database search was developed and evaluated for drug screening and confirmation in analytical toxicology context. An established LC-TOFMS screening method, in which identification relies solely on protonated molecule accurate mass measurement, isotopic pattern fit, and retention time (RT), was completed to include 1-3 qualifier ions for each analyte in the database. The qualifier ions for 431 compounds were selected from the experimental ISCID spectra, and their molecular formulae were assigned by applying SmartFormula3D and MSFragmenter software. Three qualifier ions were assigned for 64.5%, two or three for 81.4%, one for 14.8%, and none for 3.7% of the compounds studied. Comparison between ISCID LC-TOFMS and LC-TOFMS with 25 authentic autopsy urine samples showed an improved confidence level with the ISCID method, as isomeric interferences were excluded in most cases. However, some false negative (FN) results were obtained at low concentration levels close to the reporting criteria. The cut-off concentration of the ISCID method was 10-100 ng/mL with 80% of the 49 representative compounds tested, and the level was approximately two times higher than that obtained by LC ion trap MS. The presented method enables simultaneous screening and confirmation whenever at least one qualifier ion is available, as applying an accurate mass precursor ion and one product ion surpasses the standard of four identification points that is required by the current EU protocol.
    Anal Bioanal Chem. 05/2012; 403(5-403 (5)):1265.
  • Elli Tyrkkö, Anna Pelander, Ilkka Ojanperä
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    ABSTRACT: A liquid chromatography (LC) retention time prediction software, ACD/ChromGenius, was employed to calculate retention times for structural isomers, which cannot be differentiated by accurate mass measurement techniques alone. For 486 drug compounds included in an in-house database for urine drug screening by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOFMS), a retention time knowledge base was created with the software. ACD/ChromGenius calculated retention times for compounds based on the drawn molecular structure and given chromatographic parameters. The ability of the software for compound identification was evaluated by calculating the retention order of the 118 isomers, in 50 isomer groups of 2-5 compounds each, included in the database. ACD/ChromGenius predicted the correct elution order for 68% (34) of isomer groups. Of the 16 groups for which the isomer elution order was incorrectly calculated, two were diastereomer pairs and thus difficult to distinguish using the software. Correlation between the calculated and experimental retention times in the knowledge base tested was moderate, r(2)=0.8533. The mean and median absolute errors were 1.12 min, and 0.84 min, respectively, and the standard deviation was 1.04 min. The information generated by ACD/ChromGenius, together with other in silico methods employing accurate mass data, makes the identification of substances more reliable. This study demonstrates an approach for tentatively identifying compounds in a large target database without a need for primary reference standards.
    Analytica chimica acta 03/2012; 720:142-8. · 4.31 Impact Factor
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    ABSTRACT: To characterize the pharmacokinetics (PK) of oxycodone following intravenous injection and administration of three oral dosage forms (solution, capsule, and controlled-release tablet) in elderly patients (age 76-89 years) undergoing cystoscopy. This was an open, randomized study with two sequences and two visits in 15 elderly patients. The patients were given intravenous injection (over 10 min) of 5 mg of oxycodone hydrochloride trihydrate. Oxycodone hydrochloride (5 mg in all forms) was orally administered as a solution, a capsule, and a controlled-release tablet. Venous blood samples were collected up to 17 h after oxycodone administration. Population PK parameters were calculated with NONMEM VI 2.0. For intravenous injection we calculated clearance, volume of distribution at steady state, and the half-life of elimination, and for oral dosage forms also the absolute bioavailability. Clearance of the intravenous injections was 28.9 L/h; the volume of distribution at steady state and the half-life of elimination were 186 L and 5.2 h, respectively. The absolute bioavailability of oxycodone was 59 % from oral solutions, 64 % from capsules, and 55 % from controlled-release tablets. Our results indicate that, in the elderly, the bioavailability of the three different oral dosage forms of oxycodone is fairly similar.
    European Journal of Clinical Pharmacology 03/2012; 68(10):1357-63. · 2.74 Impact Factor
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    ABSTRACT: A method based on in-source collision-induced dissociation (ISCID) liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) and reverse target database search was developed and evaluated for drug screening and confirmation in analytical toxicology context. An established LC-TOFMS screening method, in which identification relies solely on protonated molecule accurate mass measurement, isotopic pattern fit, and retention time (RT), was completed to include 1-3 qualifier ions for each analyte in the database. The qualifier ions for 431 compounds were selected from the experimental ISCID spectra, and their molecular formulae were assigned by applying SmartFormula3D and MSFragmenter software. Three qualifier ions were assigned for 64.5%, two or three for 81.4%, one for 14.8%, and none for 3.7% of the compounds studied. Comparison between ISCID LC-TOFMS and LC-TOFMS with 25 authentic autopsy urine samples showed an improved confidence level with the ISCID method, as isomeric interferences were excluded in most cases. However, some false negative (FN) results were obtained at low concentration levels close to the reporting criteria. The cut-off concentration of the ISCID method was 10-100 ng/mL with 80% of the 49 representative compounds tested, and the level was approximately two times higher than that obtained by LC ion trap MS. The presented method enables simultaneous screening and confirmation whenever at least one qualifier ion is available, as applying an accurate mass precursor ion and one product ion surpasses the standard of four identification points that is required by the current EU protocol.
    Analytical and Bioanalytical Chemistry 03/2012; 403(5):1265-78. · 3.66 Impact Factor
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    ABSTRACT: Phenazepam is a long-acting benzodiazepine that, unlike other benzodiazepines, is currently not scheduled as a narcotic in Finland, most other European countries or the USA. It is used as an anxiolytic, sedative-hypnotic and anti-epileptic, mainly in Russia. In Finland, as well as in some other countries, an increase in the unauthorized use of phenazepam has been observed in recent years. In the one year period between July 1, 2010 and June 30, 2011 the prevalence of phenazepam in Finland was assessed among drivers apprehended for driving under the influence of drugs (DUID), in medico-legal autopsy cases and in police confiscations of illicit drugs. In DUID cases an LC-MS/MS method preceded by solid phase extraction was used for the determination of phenazepam. In the post-mortem investigations the sample preparation consisted of liquid-liquid extraction followed by derivatization and the determination was carried out by GC-MS. The police confiscations were analysed by GC-MS. There were 141 positive phenazepam cases among apprehended drivers, representing approximately 3.5% of all confirmed drug cases (n=4007) in this time period. The median (range) phenazepam blood concentration in DUID cases was 0.061 mg/L (0.004-3.600 mg/L). The median phenazepam concentration in cases with no concomitant stimulant use was significantly higher than the overall median concentration. Phenazepam was found in 17 medico-legal autopsy cases and the median (range) blood concentration was 0.048 mg/L (0.007-1.600 mg/L). Phenazepam was not considered by the medico-legal team to be the sole cause of death in any of the cases, the majority of them being accidental opiod overdoses. There were 26 seizures of phenazepam by the Police in the time period studied, some of the batches consisted of a mixture of phenazepam and stimulant designer drugs. The data show that phenazepam abuse is a widespread phenomenon in Finland. A typical user was a male multi-drug user in his 30s. The concentration range of phenazepam among apprehended drivers and medico-legal autopsy cases was wide and the drug was usually found along with other psychoactive drugs. Therefore, although it seems likely that phenazepam contributed to impairment of driving in some DUID cases, the extent of its effect remains unclear and further studies are needed to define the concentrations causing impairment and toxicity.
    Forensic science international 03/2012; 220(1-3):111-7. · 2.10 Impact Factor

Publication Stats

1k Citations
74 Downloads
252.57 Total Impact Points

Institutions

  • 1987–2014
    • University of Helsinki
      • • Department of Chemistry
      • • Laboratory of Analytical Chemistry
      Helsinki, Southern Finland Province, Finland
  • 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