Olof Beck

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (220)697.35 Total impact

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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; DOI:10.3109/15563650.2015.1079325 · 3.12 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; DOI:10.3109/15563650.2015.1054505 · 3.12 Impact Factor
  • Anders Helander · Shahid Ullah · Olof Beck
    Clinical Chemistry 05/2015; DOI:10.1373/clinchem.2015.239848 · 7.77 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 · 2.12 Impact Factor
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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 · 3.12 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 · 2.69 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 · 4.29 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 · 2.01 Impact Factor
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    ABSTRACT: Morphine is still the mainstay in treatment of severe pain and is metabolized in the liver mainly by glucuronidation, partly to the pharmacologically active morphine-6-glucuronide (M6G). The sulfation pathway has attracted much less attention but may also form active metabolites. The aim of the present study was to study two sulfate metabolites of morphine in humans. Urine and plasma from newborns, adult heroin addicts, and terminal cancer patients was analyzed for the presence of morphine-3-sulfate (M3S) and morphine-6-sulfate (M6S) by a new liquid chromatography – tandem mass spectrometry (LC-MS/MS) method. In addition, morphine sulfation was studied in vitro in human liver cytosol preparations. M3S was present in urine and plasma from all study groups although at lower concentrations than morphine-3-glucuronide (M3G). The plasma M3S/M3G ratio was 30 times higher in newborns than in adults indicating that the relative sulfation is more important at early stage of life. M6S was measurable in only one plasma sample from a newborn patient, and in one of the urine sample from the drug testing group. The incubation of morphine with liver cytosol extracts resulted in approximately equal rate of formation of both M3S and M6S. In conclusion, sulfation of morphine is catalyzed in human liver but this minor metabolic pathway probably lacks clinical significance. The M6S metabolite is formed at a low rate, making it undetectable in most individuals.
    12/2014; 2(6). DOI:10.1002/prp2.71
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    ABSTRACT: Background. 3-Methylmethcathinone (3-MMC) is a synthetic cathinone stimulant structurally related to the new psychoactive substance (NPS) mephedrone (4-methylmethcathinone, 4-MMC). We describe a case series of analytically confirmed intoxications involving 3-MMC presented to emergency departments in Sweden and included in the STRIDA project. Study design. Observational case series of consecutive patients with self-reported or suspected use of NPS presenting to hospitals in Sweden between August 2012 and March 2014. Methods. NPS analysis was performed by a liquid chromatography-mass spectrometry (MS)/MS method that is updated with new substances as they appear. Data on clinical features were collected during Poisons Information Centre consultations and retrieved from medical records. Results. 3-MMC was detected in 50 (6.4%) of the 786 cases included in the STRIDA project during the 20-month study period, with the peak occurring in August 2013. The age range of patients testing positive for 3-MMC was 17-49 years (median 24) and 76% of them were men. The 3-MMC concentration in serum ranged between 0.002 and 1.49 μg/mL (median, 0.091) and between 0.007 and 290 μg/mL (median, 3.05) in urine. Co-exposure to other NPS and/or traditional drugs was very common, and 3-MMC mono-intoxication was found in only 4 (8%) cases. The most frequent clinical features were tachycardia (48% of cases) and agitation (42%). Other features included a reduced level of consciousness (32%), dilated pupils (24%), hallucinations (20%), diaphoresis (12%), seizures (8%), and hyperthermia (6%). Most patients (60%) needed hospital care for only 1 day but in 8% for 3 days or longer. Conclusion. The majority of patients with analytically confirmed 3-MMC exposure had sympathomimetic features similar to those associated with mephedrone intoxication. However, the high incidence of co-exposure to other drugs makes the clinical interpretation difficult. Nevertheless, 3-MMC was associated with a high admittance rate to intensive care (30%), and detected in two cases with a fatal outcome, suggesting that 3-MMC is a harmful drug.
    Clinical Toxicology 11/2014; 53(1):1-8. DOI:10.3109/15563650.2014.981823 · 3.12 Impact Factor
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    ABSTRACT: Introduction The oral direct thrombin inhibitor dabigatran is increasingly used to prevent thromboembolic stroke in patients with atrial fibrillation (AF). Routine laboratory monitoring is currently not recommended, but measurements of dabigatran and/or its effect are desirable in certain situations. We studied dabigatran exposure and compared different tests for monitoring of dabigatran in a real-life cohort of AF patients. Material and methods Ninety AF patients (68 ± 9 years, 67% men, mean CHADS2 score 1.5) were treated with dabigatran 150 (n = 73) or 110 mg BID (n = 17). Trough plasma concentrations of total and free dabigatran by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) were compared to indirect measurements by Hemoclot thrombin inhibitors (HTI) and Ecarin clotting assay (ECA), as well as PT-INR and aPTT. Results Total plasma dabigatran varied 20-fold (12–237 ng/mL with 150 mg BID) and correlated well with free dabigatran (r2 = 0.93). There were strong correlations between LC-MS/MS and HTI or ECA (p < 0.001) but these assays were less accurate with dabigatran below 50 ng/mL. The aPTT assay was not dependable and PT-INR not useful at all. There were weak correlations between creatinine clearance (Cockcroft-Gault) and LC-MS/MS, HTI and ECA (p < 0.001 for all). A high body weight with normal kidney function was associated with low dabigatran levels. Conclusions HTI and ECA reflect the intensity of dabigatran anticoagulation, but LC-MS/MS is required to quantify low levels or infer absence of dabigatran. Most real life patients with a normal creatinine clearance had low dabigatran levels suggesting a low risk of bleeding but possibly limited protection against stroke.
    Thrombosis Research 10/2014; 134(4). DOI:10.1016/j.thromres.2014.06.016 · 2.43 Impact Factor
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    ABSTRACT: The “STRIDA” project monitors the occurrence and trends of new psychoactive substances (NPS; “Internet drugs/designer drugs/legal highs”) in Sweden, and collects information about their clinical symptoms, toxicity and associated health hazards. The initial results of the project documented a widespread use of many different NPS by mainly adolescents and young (age range 13–63 years, median 20), male (79%) adults, among cases of drug intoxications presenting at emergency departments and intensive care units across the country. The new substances were identified in samples of urine and blood by a multi-component LC-MS/MS method, and the severity of clinical symptoms were graded by the Poisoning Severity Score (PSS). Of the initial 189 samples submitted for laboratory investigation, 156 (83%) tested positive for at least one drug. Besides classical substances such as ethanol, cannabis and amphetamines, many NPS were detected comprising synthetic cannabinoid receptor agonists (“Spice”), piperazines, substituted phenethylamines, synthetic cathinones, hallucinogenic tryptamines, piperidines, opioid related substances, ketamine and related substances, and GABA analogues (in total more than 50 substances). About half of the cases were demonstrated to be multiple drug intoxications, sometimes making it hard to associate the clinical presentations with one specific substance. In conclusion, the STRIDA project has documented use of a broad variety of NPS among mainly young people all over Sweden.
    Forensic science international 10/2014; 243. DOI:10.1016/j.forsciint.2014.02.022 · 2.12 Impact Factor
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    ABSTRACT: Exhaled breath has recently been proposed as a matrix for drug testing. This study aims to further explore, develop and validate exhaled breath as a safe and effective non-invasive method for drug testing in a clinical setting. Self-reported drug use was recorded and drug testing was performed by mass spectrometry and immunochemical methods using breath, plasma and urine samples from 45 individuals voluntarily seeking treatment for recreational drug use. Cannabis was the most prevalent drug detected by any method. Urine sampling detected most cases. The exhaled breath technique was less sensitive (73%) than plasma analysis for detection of cannabis uses but captures a more recent drug intake than both plasma and urine. Exhaled breath was the preferred specimen to donate according to interview data of the participants. Testing illicit drugs with the exhaled breath sampling technique is a sufficient, non-invasive and safe alternative and complement to plasma and/or urine sampling.
    Journal of Substance Abuse Treatment 09/2014; 48(1). DOI:10.1016/j.jsat.2014.09.003 · 3.14 Impact Factor
  • Karin Nilsson · Maria Andersson · Olof Beck
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    ABSTRACT: A semi-automated method for quantification of budesonide in human plasma was developed, validated, and applied for high-volume analysis of samples in connection with a pharmacokinetic study. Protein and phospholipid removal was performed using an Ostro 96-well filter plate and subsequently combined with C18 solid-phase extraction on a Hamilton Microlab STARlet automation robot. The final extracts were evaporated to dryness and redissolved in 20% acetonitrile/water. The procedure used budesonide-d8 as internal standard and gave a 3.5-fold concentration of plasma to extract. The final extracts (5μL injected) were analyzed with selected reaction monitoring liquid chromatography-tandem mass spectrometry (LC-MS/MS) using electrospray ionization in positive mode. The chromatography system used a 100mm ACQUITY BEH UPLC column and a gradient system consisting of aqueous 0.1% formic acid and acetonitrile as organic modifier. Phospholipid removal was found to be needed during method development in order to reduce ion suppression effects from matrix and to increase method sensitivity. The measuring range was 50-5000pg/mL with and LOD 24pg/mL. Calibration response showed good linearity (correlation coefficients<0.99) over the measuring range. The absolute recovery over the sample preparation procedure was estimated to 67%. Total imprecision was <9% at three levels and accuracy was between 98.9 and 103%. The method was successfully applied for analysis of 864 study samples in a short time. The quality control samples at concentration levels 200 and 2000pg/mL gave a total imprecision of 7.4% and 4.2%, respectively, (n=95).
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 09/2014; 970C:31-35. DOI:10.1016/j.jchromb.2014.08.035 · 2.69 Impact Factor
  • A Helander · M Bäckberg · O Beck
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    ABSTRACT: Background. MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) is an opioid analgesic drug candidate developed in the 1970s that has recently been introduced as a new psychoactive substance (NPS) on the "recreational" drug market. We describe a case series of non-fatal intoxications associated with MT-45 within the Swedish STRIDA project. Study design. Observational case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals in Sweden from November 2013 to February 2014. Patients and methods. Blood and urine samples were collected from intoxicated patients presenting to emergency departments and intensive care units over the country. NPS analysis was performed by an LC-MS/MS multi-component method. Clinical data were collected when caregivers consulted the Poisons Information Centre and also retrieved from medical records. Case series. Among nine intoxications where MT-45 was detected in the biological samples, four cases were indicated to only involve MT-45, while one or several psychoactive substances were found along with MT-45 in the others. All patients were men aged 17-32 years and they commonly presented with opioid-like adverse symptoms, such as unconsciousness and respiratory depression. Naloxone appeared to have utility in the treatment of MT-45 intoxication in several cases. Three patients complained of bilateral hearing loss that in one case persisted after two weeks. Conclusion. MT-45 should be added to the growing list of harmful NPS causing life-threatening poisonings, and rapid actions taken to make it a controlled substance.
    Clinical Toxicology 09/2014; 52(8):1-4. DOI:10.3109/15563650.2014.943908 · 3.12 Impact Factor
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    ABSTRACT: Abstract AIM: Assess association between UGT2B7 polymorphism -900G>A (rs7438135, also known as -842G>A) with morphine kinetics in preterm newborns undergoing mechanical ventilation. MATERIALS & METHODS: Thirty-four infants were enrolled in a randomized clinical trial and allocated to rapid sequence intubation with remifentanil (1 µg/kg) or morphine (0.3 mg/kg). The latter group was included in our study. RESULTS: Morphine plasma concentrations at 20 min post intubation were associated with postnatal age (p = 0.017) and UGT2B7 -900G>A (p = 0.036). UGT2B7 -900A allele carriers (n = 13) had lower morphine levels compared with UGT2B7 -900G/G patients (n = 2). Morphine-3-glucuronide and morphine-6-glucuronide plasma concentrations were only found to be associated with gestational and postnatal age. However, -900A allele carriers had a higher morphine-3-glucuronide:morphine metabolic ratio compared with patients genotyped as -900G/G (p = 0.005), as determined by linear regression. CONCLUSION: Our small pilot study illustrates that in addition to gestational and postnatal age, the UGT2B7 -900G>A polymorphism significantly alters morphine pharmacokinetics in preterm infants. Original submitted 8 April 2014; Revision submitted 22 July 2014.
    Pharmacogenomics 09/2014; 15(12):1589-97. DOI:10.2217/pgs.14.115 · 3.43 Impact Factor
  • Addiction 09/2014; 109(9):1571-1572. DOI:10.1111/add.12674 · 4.60 Impact Factor
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    ABSTRACT: Breath has been investigated as an alternative matrix for detecting recent cocaine intake; however, there are no controlled cocaine administration studies that investigated the drug's disposition into breath. Breath was collected from 10 healthy adult cocaine users by asking them to breathe into a SensAbues device for 3 min before and up to 22 h following 25 mg intravenous (IV) cocaine dosing on days 1, 5, and 10, and assayed with a validated liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method to quantify breath cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), and norcocaine. The assay was linear from 25 to 1,000 pg/filter, extraction efficiencies were 83.6-126 %, intra- and inter-assay imprecision was <10.6 %, and bias was between -8.5 and 16.8 %. No endogenous or exogenous interferences were observed for more than 75 tested. Analytes were generally stable under short-term storage conditions. Ion suppression was less than 46 %. Of breath specimens collected after controlled cocaine administration, 2.6 % were positive for cocaine (26.1-66 pg/filter, 1-9.5 h), 0.72 % BE (83.3-151 pg/filter, 6.5-12.5 h), and 0.72 % EME (50-69.1 pg/filter, 6.5-12.5 h); norcocaine was not detected. Methanolic extraction of the devices themselves, after filters were removed, yielded 19.2 % positive cocaine tests (25.2-36.4 pg/device, 10 min-22 h) and 4.3 % positive BE tests (26.4-93.7 pg/device, 10 min-22 h), explaining differences between the two extraction techniques. These results suggest that the device reflects the drug in oral fluid as well as lung microparticles, while the filter reflects only drug-laden microparticles. A sensitive and specific method for cocaine, BE, EME, and norcocaine quantification in breath was developed and validated. Cocaine in breath identifies recent cocaine ingestion, but its absence does not preclude recent use.
    Analytical and Bioanalytical Chemistry 08/2014; 406(25). DOI:10.1007/s00216-014-8051-x · 3.58 Impact Factor
  • Olof Beck · Magnus Ericsson
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    ABSTRACT: The advent of LC combined with MS made it possible to design analytical methods for urine drug testing based on the very simple concept of diluting urine with an internal standard as the sole preparation procedure prior to instrumental analysis. The number of publications using this method design increased after the development of high-efficiency LC based on sub-2 μm particles. The success of this method design for drug testing, doping control and toxicological investigations of urine is now well documented and comprise both screening and confirmation methods. The nondiscriminating nature of this method design makes it even more attractive in combination with high-resolution MS for multicomponent target and general unknown analysis applications.
    Bioanalysis 08/2014; 6(17):2229-44. DOI:10.4155/bio.14.192 · 3.03 Impact Factor
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    ABSTRACT: Background. Therapeutic drug monitoring (TDM) of the antiepileptic drug valproic acid (VPA) is recommended in patients with multiple drug therapy or with concomitant disabilities to ensure treatment efficacy and avoid adverse reactions in both adults and children. The use of sampling techniques compatible with home sampling, such as dried blood spot sampling could potentially facilitate this for patients. Aim. To assess the usefulness of a bioanalytical method for quantification of VPA in dried blood spots. Materials and methods. Quantification was based on liquid chromatography-mass spectrometry (LC-MS), both for the DBS method and the plasma-based reference method. Results. The method was validated in the range 10–1200 μmol/L. Total imprecision ranged from 4.9–8.9 (%CV) and accuracy was within ± 14%. Conclusion. The validated method has potential for evaluation in therapeutic drug monitoring in combination with home sampling of DBS. The impact of spot size can be controlled through acceptance criteria and hematocrit in the range 30–60% can be accepted in sampling. Comparison of VPA levels between plasma and whole blood cannot be done without considering the blood-plasma ratio.
    Scandinavian Journal of Clinical and Laboratory Investigation 07/2014; 74(7). DOI:10.3109/00365513.2014.933360 · 2.01 Impact Factor

Publication Stats

4k Citations
697.35 Total Impact Points

Institutions

  • 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