Olof Beck

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (244)800.4 Total impact

  • Shahid Ullah · Soren Sandquist · Olof Beck ·
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    ABSTRACT: An analytical method based on high performance liquid chromatography coupled to quadrupole tandem mass spectrometry was developed for the quantitative determination of four phosphatidylcholines (PCs) in human exhaled breath particles. Analytes were conveniently collected on an electro-static polymer filter and extracted with methanol prior to analysis. Chromatographic separation was performed on a UPLC BEH phenyl column using a mobile phase consisting of water and methanol containing 4 mM ammonium formate and 0.1% ammonia. The mass spectrometer operated in positive electrospray ionization and selected reaction monitoring mode. Detection limits for PC 16:0/16:0 (DPPC), PC 16:0/18:1, PC 16:0/18:2 and PC 18:0/18:2 were <0.01 ng/filter. Method recoveries at concentration levels 0.1 and 10 ng/ filter were between 100 to 110% and 101 to 121%, respectively. Acceptable precision with co-efficients of variation <20% and accuracies of 100±20% were achieved. Identification of the individual PCs were performed based on two product ions with correct ion ratios and chromatographic retention times. The highest amount in exhaled breath was found for DPPC with median concentration 1.14 ng/filter (range 0.6 to 21 ng/filter), and median molar ratios of DPPC/PC (16:0/18:1) of 1.98 (range 0.48 to 2.75). A different pattern with lower molar ratio (~ 0.15) was found for oral fluid. The most significance of this study was to use a precolumn in the LC system and collect-ing exhaled particles in an electret polymer filter. Due to the chromatographic interference by back-ground contamination, an isolator column (PFC kit) was installed in between eluent mixer and injector to reduce the contamination. This is the first LC-MS study where method was successfully applied to analyze PCs in human exhaled breath by using a simple and convenient collection procedure.
    Analytical Chemistry 10/2015; DOI:10.1021/acs.analchem.5b03433 · 5.64 Impact Factor
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    ABSTRACT: Alcohol dependence is associated with a dysregulated dopamine system modulating reward, craving and cognition. The monoamine stabilizer (-)-OSU6162 (OSU6162) can counteract both hyper- and hypo-dopaminergic states and we recently demonstrated that it attenuates alcohol-mediated behaviors in long-term drinking rats. The present Phase II exploratory human laboratory study investigated to our knowledge for the first time the effects of OSU6162 on cue- and priming-induced craving in alcohol dependent individuals. Fifty-six alcohol dependent individuals were randomized to a 14-day-treatment period of OSU6162 or placebo after their baseline impulsivity levels had been determined using the Stop Signal Task. On Day 15, participants were subjected to a laboratory alcohol craving test comprised of craving sessions induced by: i) active - alcohol specific cues, ii) neutral stimuli and iii) priming - intake of an alcoholic beverage (0.20g ethanol/kg bodyweight). Subjective ratings of alcohol craving were assessed using the shortened version of the Desire for Alcohol Questionnaire and visual analog scales (VAS). OSU6162 treatment had no significant effect on cue-induced alcohol craving, but significantly attenuated priming-induced craving. Exploratory analysis revealed that this effect was driven by the individuals with high baseline impulsivity. In addition, OSU6162 significantly blunted the subjective liking of the consumed alcohol (VAS). Although the present 14-day-treatment period, showed that OSU6162 was safe and well tolerated, this exploratory human laboratory study was not designed to evaluate the efficacy of OSU6162 to affect alcohol consumption. Thus a larger placebo-controlled efficacyclinical trial is needed to further investigate the potential of OSU6162 as a novel medication for alcohol dependence.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 10/2015; DOI:10.1016/j.euroneuro.2015.09.018 · 4.37 Impact Factor
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    ABSTRACT: Context: In the recent years, there have been an increasing number of new psychoactive substances (NPS) available through marketing and sale on the Internet. The stimulant 3,4-methylenedioxypyrovalerone (MDPV) is a potent dopamine reuptake inhibitor, which can cause serious intoxications requiring intensive care and even fatality. This report from the STRIDA project presents the prevalence, laboratory results, and clinical features in a series of intoxications involving MDPV over a 5-year period. Study design: Observational case series of consecutive patients with admitted or suspected intake of NPS presented at hospitals in Sweden from 2010 to 2014. Patients and methods: Blood and/or urine samples were collected from intoxicated patients with admitted or suspected intake of NPS presenting at hospitals over the country. Analysis of NPS was performed by a liquid chromatography-tandem mass spectrometry multicomponent method. Clinical data were collected when caregivers consulted the Swedish Poisons Information Centre and also retrieved from medical records. The severity of poisoning was graded retrospectively using the poisoning severity score. Results: During the 5-year study period, the number of MDPV-related inquiries to the Poisons Information Centre was 662 out of a total ∼4500 suspected NPS-related inquiries (∼15%), and 201 analytically confirmed MDPV intoxications were enrolled in the study. The study period covered the period when the use of MDPV in Sweden was at its peak and also the decline to an almost zero level. The age range of patients was 18-68 (mean 36, median 35) years, and 71% were males. The MDPV concentrations in serum ranged between 1.0 ng/mL and 1509 ng/mL (mean 63.6, median 20) and between 1.0 ng/mL and 81 000 ng/mL (mean 3880, median 1160) in urine. The urinary values were also creatinine corrected for variation in urine dilution, and the MDPV/creatinine ratio ranged between 0.10 ng/mmol and 2480 ng/mmol (mean 247, median 92.6). There was a statistically significant association between the serum MDPV concentration and the urinary MDPV/creatinine ratio, for 118 cases where both data were available (r = 0.764; p < 0.0001, Spearman's rank correlation). In 30 (15%) cases, MDPV was the single psychoactive substance identified in the serum or urine specimens. In the other 171 cases, other psychoactive substances were detected together with MDPV. The additional substances (n = 61) comprised of both conventional drugs of abuse, other NPS (n = 39), pharmaceuticals, and ethanol. The cathinone-derivative alpha-pyrrolidinovalerophenone (α-PVP) was the most frequent other NPS, and was detected in 58 (29%) cases, followed by methylone in 14 (7%) cases. The main clinical manifestations reported in patients testing positive for MDPV included agitation, tachycardia (≥100/min), and hypertension (systolic blood pressure ≥140 mmHg), which were observed in 130 (67%), 106 (56%), and 65 (34%) cases, respectively. Other symptoms included hallucinations (n = 31, 16%), delirium (n = 29, 15%), hyperthermia (>39°C/102.4°F; n = 18, 10%), and rhabdomyolysis (n = 16, 8%). In MDPV intoxications with serum levels >100 ng/mL, the cases were graded as more severe and hyperthermia was less common. Conclusions: In a large number of analytically confirmed MDPV intoxications from mostly polydrug users, the urine and serum MDPV concentrations showed a high variability. The clinical features were consistent with a severe sympathomimetic toxidrome. The results also demonstrated that MDPV prevailed as a drug of abuse for a long time, after its classification as a narcotic substance and despite a high incidence of severe poisonings.
    Clinical Toxicology 10/2015; DOI:10.3109/15563650.2015.1089576 · 3.67 Impact Factor
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    ABSTRACT: The use of khat (Catha edulis) while on medication may alter treatment outcome. In particular, the influence of khat on the metabolic activities of drug-metabolizing enzymes is not known. We performed a comparative 1-way crossover study to evaluate the effect of khat on cytochrome P450 (CYP)2D6 and CYP3A4 enzyme activity. After 1 week of khat abstinence, baseline CYP2D6 and CYP3A4 metabolic activities were determined in 40 Ethiopian male volunteers using 30 mg dextromethorphan (DM) as a probe drug and then repeated after 1 week of daily use of 400 g fresh khat leaves. Urinary concentrations of cathinone and cathine were determined to monitor the subjects' compliance to the study protocol. Genotyping for CYP2D6*3 and CYP2D6*4 was done. Plasma DM, dextrorphan and 3-methoxymorphinan concentrations were quantified. CYP2D6 and CYP3A4 enzyme activities were assessed by comparing plasma log DM/dextrorphan and log DM/methoxymorphinan metabolic ratio (MR) respectively in the presence and absence of khat. Cytochrome 2D6 MR was significantly increased from baseline by concurrent khat use (paired t test, P = 0.003; geometric mean ratio, 1.38; 95% confidence interval [95% CI], 1.12-1.53). Moreover, the inhibition of CYP2D6 activity by khat was more pronounced in CYP2D6*1/*1 compared with CYP2D6*1/*4 genotypes (P = 0.01). A marginal inhibition of CYP3A4 activity in the presence of khat was observed (P = 0.24). The mean percentage increase of CYP2D6 and CYP3A4 MR from baseline by khat use was 46% (95% CI, 20-72) and 31% (95% CI, 8-54), respectively. This is the first report linking khat use with significant inhibition of CYP2D6 metabolic activity in humans.
    Journal of clinical psychopharmacology 10/2015; DOI:10.1097/JCP.0000000000000413 · 3.24 Impact Factor
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    L. Franzén · M. Bäckberg · O. Beck · A. Helander ·

    Toxicology Letters 10/2015; 238(2):S160. DOI:10.1016/j.toxlet.2015.08.496 · 3.26 Impact Factor
  • M. Bäckberg · O. Beck · A. Helander ·

    Toxicology Letters 10/2015; 238(2):S5. DOI:10.1016/j.toxlet.2015.08.032 · 3.26 Impact Factor
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    ABSTRACT: Exhaled breath (EB) is a promising matrix for bioanalysis of non-volatiles and has been routinely implemented for drugs of abuse analysis. Nothing is known regarding the pharmacokinetics of therapeutics and their metabolites in EB. Therefore, we used tramadol as a model drug. Twelve volunteers received a single oral dose of tramadol and repeated sampling of EB, plasma, and oral fluid (OF) was done for 48hours using a particle filter device for EB and the Quantisal-device for OF. Samples were analyzed with LC-MS/MS and the pharmacokinetic correlations between matrices were investigated. The initial tramadol half-life in EB was shorter than in plasma but it reappeared in EB after 8-11hours. The ratio of O-desmethyltramadol to tramadol was considerably lower in EB/OF compared to plasma. This pilot study compared for the first time the pharmacokinetics of a therapeutic drug+active metabolite in different biomatrices including EB and demonstrated its potential for bioanalysis.
    Biochemical pharmacology 09/2015; 98(3). DOI:10.1016/j.bcp.2015.09.008 · 5.01 Impact Factor
  • Gabriel Lenk · Jonas Hansson · Olof Beck · Niclas Roxhed ·
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    ABSTRACT: Inhomogeneous sample distribution in DBS is a problem for accurate quantitative analysis of DBS, and has often been explained by chromatographic effects. We present a model describing formation of inhomogeneous DBS during drying of the spot caused by higher evaporation rates of water at the edge as compared with the center. Color intensity analysis shows that the relative humidity and DBS card position affect the homogeneity of DBS. The so-called 'coffee-stain effect' explains the typical distribution pattern of analytes with higher concentrations measured along the edge of DBS as compared with the center. The driving mechanism and potential influencing factors should be considered when addressing the inhomogeneity of DBS in the future.
    Bioanalysis 09/2015; 7(16):1977-85. DOI:10.4155/bio.15.135 · 3.00 Impact Factor
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    ABSTRACT: DBS samples collected from a fingerprick typically vary in volume and homogeneity and hence make an accurate quantitative analysis of DBS samples difficult. We report a prototype which first defines a precise liquid volume and subsequently stores it to a conventional DBS matrix. Liquid volumes of 2.2 µl ± 7.1% (n = 21) for deionized water and 6.1 µl ± 8.8% (n = 15) for whole blood have been successfully metered and stored in DBS paper. The new method of collecting a defined volume of blood by DBS sampling has the potential to reduce assay bias for the quantitative evaluation of DBS samples while maintaining the simplicity of conventional DBS sampling.
    Bioanalysis 09/2015; 7(16):2085-94. DOI:10.4155/bio.15.134 · 3.00 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA2095. DOI:10.1183/13993003.congress-2015.PA2095 · 7.64 Impact Factor
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    ABSTRACT: Therapeutic drug monitoring of antiepileptic drugs in children with epilepsy assists for personalized drug therapy but require numerous patient visits for venous blood sampling. DBS is an alternative matrix applicable to home sampling which can save time and reduce stress for this patient group. A fast LC-MS/MS method for quantification of carbamazepine, lamotrigine and valproic acid based on DBS sampling was developed. The method showed linearity in therapeutically relevant concentration ranges and compatible with unknown volume sampling and expected hematocrit range of the patient group. A LC-MS/MS method for the three most commonly used antiepileptic drugs has been fully validated and clinically applied on DBSs from patients at the neuropediatric clinic at Karolinska University Hospital.
    Bioanalysis 09/2015; 7(16):2031-9. DOI:10.4155/bio.15.99 · 3.00 Impact Factor
  • Matilda Bäckberg · Olof Beck · Anders Helander ·
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    ABSTRACT: 3-Methoxy-phencyclidine (3-MeO-PCP) and 4-methoxy-phencyclidine (4-MeO-PCP) are analogs of and drug substitutes for the dissociative substance PCP ("Angel dust"), a recreational drug that was most popular in the 1970s. In Sweden, use of methoxylated PCP analogs was noted starting in mid-2013, according to statistics from the Poisons Information Centre. The objective of this case series was to present clinical and bioanalytical data from analytically confirmed non-fatal intoxications associated with 3-MeO-PCP and/or 4-MeO-PCP within the STRIDA project. Observational case series of consecutive patients with self-reported or suspected exposure to new psychoactive substances (NPS) and who require hospital care. Blood and urine samples were collected from intoxicated patients presenting at emergency departments (ED) or intensive care units (ICU) all over Sweden. NPS analysis was performed by multicomponent liquid chromatographic-tandem mass spectrometric (LC-MS/MS) and LC-high-resolution MS (LC-HRMS) methods. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. The Poisons Information Centre registered its first call related to methoxylated PCP analogs in July 2013, while analytically confirmed cases first appeared in October 2013. From July 2013 to March 2015, 1243 cases of suspected NPS intoxication originating from ED or ICU were enrolled in the STRIDA project. During the 21-month period, 56 (4.5%) patients tested positive for 3-MeO-PCP and 11 (0.9%) for 4-MeO-PCP; 8 of these cases involved both substances. The 59 patients were aged 14-55 (median: 26) years and 51 (86%) were men. Co-exposure to other NPSs and/or classical drugs of abuse was common with only 7 cases (12%) indicated to be 3-MeO-PCP single-substance intoxications; prominent clinical signs seen in the latter cases were hypertension (systolic blood pressure ≥ 140 mmHg; 7 cases), tachycardia (≥ 100/min; 5 cases), and altered mental status (4 cases) including confusion, disorientation, dissociation, and/or hallucinations. Mixed-drug users displayed not only the same clinical features, but also more sympathomimetic effects including agitation (38%) and dilated pupils (33%). Patients testing positive for 3-/4-MeO-PCP were typically under medical care for 1-2 days (85%), and 37% of all cases were graded as severe intoxications (Poisoning Severity Score 3). Besides standard supportive therapy, 49% of the patients were treated with benzodiazepines and/or propofol. Laboratory analysis constitutes an important basis for the assessment of NPS hazard and availability. The adverse effects noted in cases of acute intoxications involving 3- and/or 4-MeO-PCP resembled those of other dissociatives such as PCP, ketamine, and methoxetamine. However, similar to intoxications involving other NPS, poly-substance use was found to be common.
    Clinical Toxicology 08/2015; 53(9):1-9. DOI:10.3109/15563650.2015.1079325 · 3.67 Impact Factor
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    ABSTRACT: The supply of unregulated "new psychoactive substances" (NPS) has shown a steady increase over the past six years. This report from the Swedish STRIDA project describes analytically confirmed non-fatal intoxications involving butyrfentanyl (butyrylfentanyl) or 4-fluorobutyrfentanyl (para-fluorobutyrfentanyl), two fentanyl analogues recently introduced as NPS opioids. Observational case series of consecutive patients with suspected acute NPS exposure and requiring hospital care from all over Sweden. From May 2014 to January 2015, blood and urine samples were obtained from four intoxication cases involving butyrfentanyl and one case involving 4-fluorobutyrfentanyl (men, 19-30 years) presenting in emergency departments (ED) or intensive care units (ICU). Laboratory analysis of serum and/or urine samples was performed by multi-component liquid chromatography-mass spectrometry methods. Data on clinical features were collected during consultations with the Poisons Information Centre and retrieved from medical records. Of the five patients, two were discharged home from the ED and three were admitted to the ICU, of whom two required intubation and mechanical ventilation. Clinical features included typical opioid symptoms such as unconsciousness, respiratory depression, and apnea. In one case, naloxone successfully countered the effects. All patients were discharged the same or the following day. Butyrfentanyl was detected in two serum (0.6 and 0.9 ng/mL) and three urine (2.0-65.6 ng/mL) samples from three of four cases; three cases also contained fentanyl. In the 4-fluorobutyrfentanyl case, the substance was detected in serum (∼15 ng/mL) and urine (∼10 ng/mL). In four cases, other NPS and/or classical drugs were also detected. Analysis of two "butyrfentanyl" NPS products (nasal spray and powder) brought to hospital by patients showed that the 10-fold more potent fentanyl was the main active ingredient (∼7.5-10-fold higher amount) in both. Typical and potentially life-threatening opioid toxicity was seen in acute intoxications involving butyrfentanyl, 4F-butyrfentanyl, and fentanyl. The incorrect labelling of butyrfentanyl NPS products which instead mainly contained fentanyl is alarming, given the narrow range between a safe and a lethal dose for opioids.
    Clinical Toxicology 06/2015; 53(7). DOI:10.3109/15563650.2015.1054505 · 3.67 Impact Factor
  • Anders Helander · Shahid Ullah · Olof Beck ·

    Clinical Chemistry 05/2015; 61(7). DOI:10.1373/clinchem.2015.239848 · 7.91 Impact Factor
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    ABSTRACT: Heroin is de-acetylated in the body to morphine in two steps. The intermediate 6-acetylmorphine (6-AM) is formed rapidly and is considered important for the pharmacological effect of heroin. In urine drug testing, an atypical pattern of morphine and 6-AM is known to occur in low frequency. The aim of this study was to investigate this atypical pattern in more detail and to identify responsible substances for a possible inhibition of the conversion from 6-AM to morphine. Urine samples were selected from a routine flow of samples sent for drug testing. Out of 695 samples containing morphine and 6-acetylmorphine, 11.5% had the atypical pattern of a 6-AM to morphine ratio above 0.26 as derived from a bimodal frequency distribution. An in vitro study of the conversion of 6-acetylmorphine to morphine in human liver homogenates demonstrated that a number of known carboxylesterase inhibitors were able to inhibit the reaction mimicking the situation in vivo. Compound 3 (3,6-Dimethoxy-4-acetoxy-5-[2-(N-methylacetamido)ethyl]phenanthrene) a substance formed from thebaine during the production of heroin was found to be a strong inhibitor. Liquid chromatography-mass spectrometry was used to identify possible inhibitors present in vivo. This part of the investigation demonstrated that several components may contribute to the effect. It is concluded that inhibition of liver carboxylesterase activity is a possible mechanism causing the atypical pattern and that one candidate compound is the result of the heroin production process. An inhibition of 6-AM metabolism is likely to increase the pharmacological effect of heroin and may be related to a higher risk of lethal toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Forensic science international 05/2015; 252. DOI:10.1016/j.forsciint.2015.05.002 · 2.14 Impact Factor
  • Anders Helander · Olof Beck · Matilda Bäckberg ·
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    ABSTRACT: Diphenidine (1-(1,2-diphenylethyl)piperidine) and its 2-methoxylated derivative methoxphenidine (MXP, 2-MeO-diphenidine) are substances with dissociative effects that were recently introduced for "recreational" purpose through the online-based sale of new psychoactive substances (NPS). A number of analytically confirmed non-fatal intoxications associated with diphenidine or MXP have occurred in Sweden and were included in the STRIDA project. Observational case series of consecutive patients with admitted or suspected intake of NPS and requiring intensive treatment in an emergency room and hospitalization in Sweden. Blood and urine samples were collected from intoxicated patients presenting at emergency departments all over the country. NPS analysis was performed by multi-component liquid chromatography-mass spectrometry methods. Data on clinical features were collected during telephone consultations with the Poisons Information Centre and retrieved from medical records. Information was also obtained from online drug discussion forums. Over a 12-month period from January to December 2014, 750 cases of suspected NPS intoxication originating from emergency departments were enrolled in the STRIDA project of which 14 (1.9%) tested positive for diphenidine and 3 (0.4%) tested positive for MXP. Co-exposure to several other NPS (e.g., 5-/6-(2-aminopropyl)benzofuran, 2-4-bromomethcathinone, butylone, 3,4-dichloromethylphenidate, 5-methoxy-N-isopropyltryptamine, methiopropamine, and α-pyrrolidinopentiothiophenone), also including other dissociative substances (3-/4-methoxyphencyclidine), and classical drugs of abuse (e.g., cannabis and ethanol) was documented in 87% of these cases. The 17 patients were aged 20-48 (median: 32) years, and 13 (76%) were men. They commonly presented with hypertension (76%), tachycardia (47%), anxiety (65%), and altered mental status (65%) including confusion, disorientation, dissociation, and/or hallucinations. Eight patients (47%) displayed severe intoxication (Poisoning Severity Score 3). The diphenidine- or MXP-positive patients required hospitalization for 1-3 (median: 2) days. In addition to standard supportive therapy, half of the cases were treated with benzodiazepines and/or propofol. The adverse effects noted in analytically confirmed cases of NPS intoxication involving diphenidine or MXP were similar to those reported for other dissociative substances such as ketamine and methoxetamine. However, the high proportion of polysubstance use might have played a role in the intoxication and clinical features in some cases.
    Clinical Toxicology 04/2015; 53(5):1-8. DOI:10.3109/15563650.2015.1033630 · 3.67 Impact Factor
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    ABSTRACT: A mass spectrometric method for drugs of abuse testing in exhaled breath employing a sampling device collecting aerosol particles was developed and applied in routine use. Analytes covered were amphetamine, methamphetamine, 6-acetylmorphine, morphine, cocaine, benzoylecgonine, diazepam, oxazepam and tetrahydrocannabinol. The method involved eluting drugs from the collection filter with methanol, quantification using deuterated analogs as internal standards, reversed phase chromatography with gradient elution, positive electrospray ionization and monitoring of two product ions per analyte in selected reaction monitoring mode. The measuring range was 6.0-1000pg/filter. The intra- and inter-assay imprecision expressed as the coefficient of variation was less than 7%. Influence from matrix was noted for most compounds but was compensated for the use of co-eluting internal standards. The LLOQ was 6.0pg/filter with intra-assay CV <5% and accuracy within 99-102% for all analytes. No chromatographic interference was observed in 20 negative control samples. The LC-MS/MS method was successfully applied for measuring drugs in unknown samples collected for the purpose of drug testing. Among the 1096 analyzed samples analytical findings were made in breath in 39 cases (3.6%). Most frequently found substances were the following: amphetamine (25 cases) methamphetamine (10 cases), THC (8 cases), cocaine (4 cases), benzoylecgonine (2 cases) and diazepam (2 cases). In conclusion, a fully validated and robust screening method suitable for the routine measurement of drugs of abuse in exhaled breath with a simple procedure for specimen collection and sample preparation was successfully developed. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Chromatography B 02/2015; 985C. DOI:10.1016/j.jchromb.2015.01.032 · 2.73 Impact Factor
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    ABSTRACT: Here we rationally evaluate surface-enhanced Raman spectroscopy (SERS) substrates in terms of limit of detection (LOD), limit of identification (LOI) and dynamic range for ten common narcotic drug analytes. The drugs were amphetamine, cocaine, methadone, diazepam, methylphenidate, oxazepam, tramadol, morphine, buprenorphine and 6-monoacetylmorphine. A Raman microscope system was complemented with portable instrumentation, both in conjunction with commercial SERS substrates, and, by vibrational peak assignments, the functionality of substrates and pureness of samples was ensured. The dynamic range is explored qualitatively by concentration series measurements, where the Langmuir adsorption isotherm provided good fits. Moreover, an output fit parameter, the inverse of Langmuir constant, was found to roughly scale with LOD and can therefore be helpful in SERS substrate evaluations. Four different statistical methodologies were tested to estimate LOD: (i) a general formula to calculate a one-sided prediction interval for the mean value of blanks (LODB), (ii–iii) calculated from a one-sided prediction interval (at significance level 0.05) of a linear regression line, where the obtained limit of detection in the signal domain was sometimes outside the linear concentration range, which is why the corresponding concentration was calculated from (ii) a linear calibration curve (LODLR) and (iii) a non-linear calibration curve (LODNR), and (iv) using receiver operating characteristic (ROC) curves to estimate LODROC. Here, a new optimization approach was introduced for LODROC estimation, based on interpolation and thus better suited to handle a few data points spanning a large concentration range. LOI was assessed by discriminant analysis of partial least squares (PLS-DA) classification for seven of the drug compounds using PLS-DA, and the extracted LOIs were found to be higher than the LODs and were varying with respect to accuracy of the model which is strongly correlated to the probability of false positive detection that can be accepted.
    Sensors and Actuators B Chemical 02/2015; 207. DOI:10.1016/j.snb.2014.09.116 · 4.10 Impact Factor
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    ABSTRACT: Aim: Exhaled breath has recently been identified as a possible matrix for drug testing. This study explored the potential of this new method for compliance monitoring of patients being treated for dependence disorders. Methods: Outpatients in treatment programs were recruited for this study. Urine was collected as part of clinical routine and a breath sample was collected in parallel together with a questionnaire about their views of the testing procedure. Urine was analyzed for amphetamines, benzodiazepines, cannabis, cocaine, buprenorphine, methadone and opiates using CEDIA immunochemical screening and mass spectrometry confirmation. The exhaled breath was collected using the SensAbues device and analyzed by mass spectrometry for amphetamine, methamphetamine, diazepam, oxazepam, tetrahydrocannabinol, cocaine, benzoylecgonine, buprenorphine, methadone, morphine, codeine and 6-acetylmorphine. Results: A total of 122 cases with parallel urine and breath samples were collected; 34 of these were negative both in urine and breath. Out of 88 cases with positive urine samples 51 (58%) were also positive in breath. Among the patients on methadone treatment, all were positive for methadone in urine and 83% were positive in breath. Among patients in treatment with buprenorphine, 92% were positive in urine and among those 80% were also positive in breath. The questionnaire response documented that in general, patients accepted drug testing well and that the breath sampling procedure was preferred. Conclusion: Compliance testing for the intake of prescribed and unprescribed drugs among patients in treatment for dependence disorders using the exhaled breath sampling technique is a viable method and deserves future attention.
    Scandinavian Journal of Clinical and Laboratory Investigation 01/2015; 75(2):1-6. DOI:10.3109/00365513.2014.993336 · 1.90 Impact Factor
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    ABSTRACT: Drugs of abuse testing is used in various areas of society for detection and follow-up of drug use. In routine laboratory drug testing, immunoassays are employed for initial screening of specimens to indicate the presence of drugs. To confirm a positive screening test, a secondary analysis by mass spectrometry is performed. The »cut-off« is the pre-defined concentration threshold of a drug or drug metabolite above which the sample is considered positive. A reading below this level implies a negative test result. Swedish drug testing laboratories currently employ varying cut-offs to distinguish between a positive and a negative test result. Because a positive drug test may have serious legal consequences to the individual, it is of importance that testing is performed and judged equally, regardless of where it is performed. A national harmonization of cut-offs is therefore warranted. Based on data from four major Swedish drug testing laboratories, and considering the recommendations in international guidelines, a proposal for national harmonization of urine cut-offs for the most common set of drugs of abuse is presented.
    Lakartidningen 01/2015; 112(39).

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4k Citations
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  • 1990-2015
    • Karolinska University Hospital
      • • Department of Clinical Pharmacology
      • • Department of Clinical Microbiology
      Tukholma, Stockholm, Sweden
  • 1975-2015
    • Karolinska Institutet
      • • Department of Laboratory Medicine
      • • Department of Clinical Neuroscience
      • • Department of Clinical Pharmacology
      Solna, Stockholm, Sweden
  • 2007
    • Stockholm University
      • The Centre for Social research on Alcohol and Drugs (SoRAD)
      Tukholma, Stockholm, Sweden
  • 2004
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
  • 1996
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden
  • 1992
    • Capio S:t Görans sjukhus
      Tukholma, Stockholm, Sweden
  • 1988
    • Stanford University
      • Department of Psychiatry and Behavioral Sciences
      Stanford, California, United States
  • 1985-1986
    • Stanford Medicine
      • Department of Psychiatry and Behavioral Sciences
      Stanford, California, United States