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  1. AU="Concheiro, Marta"
  2. AU="Kang, Ji-Hoon"
  3. AU="González-Gómez, Julio César"
  4. AU="Eisinger, Felix"
  5. AU="van Arkel, Gijs H J"
  6. AU="Dukkipati, Haripriya"
  7. AU="Mansoor, Farheen"
  8. AU="Stanton, Clive"
  9. AU=Herholz K AU=Herholz K
  10. AU="Marichal, Axel"
  11. AU="Camon, Ana M"
  12. AU="Randall, Michael D"

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  1. Artikel ; Online: Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method including 25 novel synthetic opioids in hair and subsequent analysis of a Swiss opioid consumer cohort.

    Polke, Max / Concheiro, Marta / Cooper, Gail / Bogdal, Christian / Baumgartner, Markus R / Krämer, Thomas / Binz, Tina M

    Drug testing and analysis

    2024  

    Abstract: Major public health concern is raised by the evidence that common drugs like heroin are now frequently laced or replaced with highly potent novel synthetic opioids (NSOs). The objective of this study was to explore the prevalence and patterns of NSOs in ... ...

    Abstract Major public health concern is raised by the evidence that common drugs like heroin are now frequently laced or replaced with highly potent novel synthetic opioids (NSOs). The objective of this study was to explore the prevalence and patterns of NSOs in a cohort of Swiss opioid users by hair analysis. Hair analysis is considered an ideal tool for retrospective consumption monitoring. Hair samples from 439 opioid users in Zurich were analyzed. Study inclusion required a previous positive hair test result for heroin metabolites, oxycodone, fentanyl, methadone, or tramadol. The samples were extracted with a two-step extraction procedure, followed by a targeted LC-MS/MS (QTRAP® 6500+) analysis in multiple reaction monitoring mode for a total of 25 NSOs. The method underwent full validation and demonstrated good selectivity and sensitivity with limits of detection (LOD) as low as 0.1 pg/mg. The analyzed sample cohort demonstrated a positivity rate for NSOs of 2.5%, including the following NSOs: butyrylfentanyl, acrylfentanyl, furanylfentanyl, methoxyacetylfentanyl, ocfentanil, U-47700, isobutyrylfentanyl and benzylfentanyl. Furthermore, we were able to identify specific consumption patterns among drug users. The results indicate that hair analysis is a valuable tool for investigating the prevalence of NSOs in drug-using populations, which seems to be low in the case of Swiss opioid users. Nevertheless, the results highlight the need for sensitive analytical detection methods in forensic toxicology to identify and monitor substance distribution in different populations.
    Sprache Englisch
    Erscheinungsdatum 2024-02-21
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2462336-2
    ISSN 1942-7611 ; 1942-7603
    ISSN (online) 1942-7611
    ISSN 1942-7603
    DOI 10.1002/dta.3663
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Drug exposure during pregnancy: analytical methods and toxicological findings.

    Concheiro, Marta / Huestis, Marilyn A

    Bioanalysis

    2018  Band 10, Heft 8, Seite(n) 587–606

    Abstract: Drug use during pregnancy constitutes a major preventable worldwide public health issue. Birth defects, growth retardation and neurodevelopmental disorders are associated with tobacco, alcohol or drugs of abuse exposure during pregnancy. Besides these ... ...

    Abstract Drug use during pregnancy constitutes a major preventable worldwide public health issue. Birth defects, growth retardation and neurodevelopmental disorders are associated with tobacco, alcohol or drugs of abuse exposure during pregnancy. Besides these adverse health effects, drug use during pregnancy also raises legal and social concerns. Identification and quantification of drug markers in maternal and newborn biological samples offers objective evidence of exposure and complements maternal questionnaires. We reviewed the most recent analytical methods for quantifying drugs of abuse, tobacco, alcohol and psychotropic drugs in maternal, newborn and maternal-fetal unit biological samples by gas and liquid chromatography coupled to mass spectrometry. In addition, manuscripts comparing the usefulness of different biological samples to detect drug exposure during pregnancy were reviewed.
    Mesh-Begriff(e) Female ; Humans ; Maternal Exposure/adverse effects ; Pregnancy
    Sprache Englisch
    Erscheinungsdatum 2018-03-21
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ISSN 1757-6199
    ISSN (online) 1757-6199
    DOI 10.4155/bio-2017-0260
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Determination of 30 Synthetic Cathinones in Postmortem Blood Using LC-MS-MS.

    Lau, Timothy / Concheiro, Marta / Cooper, Gail

    Journal of analytical toxicology

    2020  Band 44, Heft 7, Seite(n) 679–687

    Abstract: Synthetic cathinones, commonly referred to as "bath salts," are powerful amphetamine-like psychostimulants, and new derivatives are constantly appearing in the illicit market to evade judicial consequences. To keep up with these new stimulant drugs, a ... ...

    Abstract Synthetic cathinones, commonly referred to as "bath salts," are powerful amphetamine-like psychostimulants, and new derivatives are constantly appearing in the illicit market to evade judicial consequences. To keep up with these new stimulant drugs, a low-sample-size liquid chromatography-tandem mass spectrometry method was validated to quantify 30 synthetic cathinones in postmortem blood including N-ethylpentylone and eutylone. Mixed mode cation exchange solid-phase extraction using 0.25 mL postmortem blood was performed followed by detection using a triple quadrupole mass spectrometer operating electrospray ionization in positive mode. The reversed-phase chromatographic separation was achieved in 16 min, resolving all isobaric compounds. The linear range of the calibration curve was 1-500 ng/mL (R  2 > 0.99) for all compounds. Limit of quantification (LOQ) and limit of detection were determined to be at 1 ng/mL. Both imprecision and bias were evaluated and had met all allowed criteria (CV and bias <20%). No matrix effect was observed with values ranging from -5.1 to 13.3% (CV 11.4-17.5%, n = 10). Extraction efficiency (84.9-91.5%) and process efficiency (86.1-102.6%) were satisfactory, except for 4-chloroethcathinone which was 63 and 64.9%, respectively. No carryover after the upper LOQ was detected. Neither endogenous nor exogenous interferences were observed. Both dilution integrity and stability (24 h) yielded acceptable results. This method was applied to 18 postmortem cases received between 2015 and 2019. Eight different synthetic cathinones were detected in selected postmortem cases within the past 5 years, showing a wide range of concentrations from 1.4 to >500 ng/mL. While ethylone and methylone were detected in 2015, cases between 2016 and 2017 were predominantly butylone, dibutylone, pentylone and N-ethylpentylone which had also exhibited a significant increase in 2018. To our knowledge, this method is the most comprehensive methodology for the determination of up-to-date synthetic cathinones currently available in whole blood.
    Mesh-Begriff(e) Alkaloids/analysis ; Chromatography, Liquid ; Forensic Toxicology ; Humans ; Limit of Detection ; Substance Abuse Detection ; Tandem Mass Spectrometry
    Chemische Substanzen Alkaloids ; cathinone (540EI4406J)
    Sprache Englisch
    Erscheinungsdatum 2020-06-26
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 752391-9
    ISSN 1945-2403 ; 0146-4760
    ISSN (online) 1945-2403
    ISSN 0146-4760
    DOI 10.1093/jat/bkaa071
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Distribution of synthetic opioids in postmortem blood, vitreous humor and brain

    Chesser, Rachel / Concheiro, Marta / Cooper, Gail / Pardi, Justine

    Forensic science international. 2019 Dec., v. 305

    2019  

    Abstract: In the US, the use of synthetic opioids (e.g. fentanyl and derivatives) has become an increasing health issue with thousands of overdose deaths being observed since 2013. With the high mortality rate associated with these substances, postmortem analyses ... ...

    Abstract In the US, the use of synthetic opioids (e.g. fentanyl and derivatives) has become an increasing health issue with thousands of overdose deaths being observed since 2013. With the high mortality rate associated with these substances, postmortem analyses and interpretation of synthetic opioids has become extremely important. However, due to the novelty of these compounds, the available data are limited and provides challenges to toxicologists. The objectives of this study were (1) to develop and validate analytical methods for the determination of synthetic opioids in vitreous humor and brain, and (2) to investigate the postmortem distribution of new synthetic opioids in blood, vitreous humor, and brain tissue. Vitreous humor (0.5mL) and brain tissue (5g) homogenized in water (diluted 1:3, w/w) were extracted by mixed mode cation exchange-reversed phase solid phase extraction. Extracts were analyzed by liquid chromatography tandem mass spectrometry (LC–MSMS). The chromatographic separation was performed by reversed-phase with 0.1% formic acid in water and in acetonitrile as mobile phases in gradient mode, with a total run time of 21min. Data were acquired with ESI+ in dynamic multiple reaction mode (dMRM), monitoring 2 transitions per compound. The methods were succesfully validated following SWGTOX guidelines, with limits of quantification of 0.1ng/mL in vitreous humor and 0.1ng/g in brain. Fifty-eight authentic case samples from the New York City Office of the Chief Medical Examiner (NYC-OCME) were analyzed to assess the distribution and detectability of synthetic opioids in these postmortem samples. Of the fifteen synthetic opioids included in the method, six synthetic opioids and metabolites (4-ANPP, acetylfentanyl, fentanyl, furanylfentanyl, norfentanyl, U-47700) were detected in the authentic cases. Concentrations for most analytes were within the 0.1 to 100ng/mL or ng/g calibration range across all three matrices, with only concentrations from acetylfentanyl and U-47700 exceeding 100ng/mL or ng/g. The highest concentrations were observed in brain (except norfentanyl), followed by blood and vitreous humor. Most analytes were detected in all three matrices in a given case. This was followed by detection of an analyte in combinations of brain and another matrix or brain only. Through the case analyses, vitreous humor and brain demonstrated to be viable alternatives to blood when performing postmortem analyses of synthetic opioids. Brain exhibited a higher detectability for most analytes when compared to blood and vitreous humor.
    Schlagwörter acetonitrile ; blood ; brain ; cations ; chemical species ; fentanyl ; formic acid ; guidelines ; liquid chromatography ; metabolites ; monitoring ; mortality ; narcotics ; overdose ; solid phase extraction ; tandem mass spectrometry ; New York
    Sprache Englisch
    Erscheinungsverlauf 2019-12
    Erscheinungsort Elsevier B.V.
    Dokumenttyp Artikel
    ZDB-ID 424042-x
    ISSN 1872-6283 ; 0379-0738
    ISSN (online) 1872-6283
    ISSN 0379-0738
    DOI 10.1016/j.forsciint.2019.109999
    Datenquelle NAL Katalog (AGRICOLA)

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  5. Artikel ; Online: Validation of an LC-MS/MS Method for the Quantification of 13 Designer Benzodiazepines in Blood.

    Mei, Victoria / Concheiro, Marta / Pardi, Justine / Cooper, Gail

    Journal of analytical toxicology

    2019  Band 43, Heft 9, Seite(n) 688–695

    Abstract: The misuse of designer benzodiazepines, as an alternative to prescription benzodiazepines and for drug-facilitated sexual assaults, has emerged as a growing threat, due in part to the ease of purchasing these drugs on the internet at low prices. Causing ... ...

    Abstract The misuse of designer benzodiazepines, as an alternative to prescription benzodiazepines and for drug-facilitated sexual assaults, has emerged as a growing threat, due in part to the ease of purchasing these drugs on the internet at low prices. Causing concern for safety is the lack of dosage information resulting in users self-medicating, often leading to unintended overdoses, coma or death at higher doses. With limited published data regarding the quantification of designer benzodiazepines in forensic cases, a method was validated for the determination of 13 designer benzodiazepines in postmortem blood, to add to the in-house method that already included a limited number of common designer benzodiazepines. The developed method included 3-hydroxyphenazepam, clobazam, clonazolam, delorazepam, deschloroetizolam, diclazepam, flualprazolam, flubromazepam, flubromazolam, flunitrazolam, meclonazepam, nifoxipam and pyrazolam in 0.5 mL postmortem blood using liquid chromatography-tandem mass spectrometry. The analytes were treated with solid phase extraction before undergoing separation on a C18 column and analyzed on the mass spectrometer in electrospray positive mode using multiple reaction monitoring. The linear range of the calibration curve was 1-200 ng/mL and up to 500 ng/mL for 3-hydroxyphenazepam, clobazam, flubromazepam and pyrazolam. The limits of detection and quantitation were 0.5 ng/mL (signal-to-noise ratio >3) and 1 ng/mL, respectively. The calculated bias, intra-day imprecision, relative standard deviation (RSD) and inter-day imprecision RSD were ±12%, 3-20% and 4-21%. Matrix effects ranged from -52% to 33% with RSD values ranging from 3-20%, indicating consistent effects throughout multiple sources. Recovery ranged from 35 to 90%, where only two compounds were <50%. Other parameters tested included carryover, stability, interference and dilution integrity, which all yielded acceptable results. With the application of this method to blood specimens from the New York City Office of Chief Medical Examiner, this validated method proved to be simple, reproducible, sensitive and robust.
    Mesh-Begriff(e) Benzodiazepines/blood ; Chromatography, Liquid/methods ; Diazepam/analogs & derivatives ; Humans ; Nordazepam/analogs & derivatives ; Substance Abuse Detection/methods ; Tandem Mass Spectrometry/methods
    Chemische Substanzen 2-chlorodiazepam (070818R7PB) ; Benzodiazepines (12794-10-4) ; flubromazolam (1BF1HN5GWD) ; Nordazepam (67220MCM01) ; deschloroetizolam (69HF7J354D) ; 3-hydroxyphenazepam (70030-11-4) ; pyrazolam (8LH16383PK) ; chlordesmethyldiazepam (O91W32476G) ; Diazepam (Q3JTX2Q7TU)
    Sprache Englisch
    Erscheinungsdatum 2019-11-18
    Erscheinungsland England
    Dokumenttyp Journal Article ; Validation Study
    ZDB-ID 752391-9
    ISSN 1945-2403 ; 0146-4760
    ISSN (online) 1945-2403
    ISSN 0146-4760
    DOI 10.1093/jat/bkz063
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Distribution of synthetic opioids in postmortem blood, vitreous humor and brain.

    Chesser, Rachel / Pardi, Justine / Concheiro, Marta / Cooper, Gail

    Forensic science international

    2019  Band 305, Seite(n) 109999

    Abstract: In the US, the use of synthetic opioids (e.g. fentanyl and derivatives) has become an increasing health issue with thousands of overdose deaths being observed since 2013. With the high mortality rate associated with these substances, postmortem analyses ... ...

    Abstract In the US, the use of synthetic opioids (e.g. fentanyl and derivatives) has become an increasing health issue with thousands of overdose deaths being observed since 2013. With the high mortality rate associated with these substances, postmortem analyses and interpretation of synthetic opioids has become extremely important. However, due to the novelty of these compounds, the available data are limited and provides challenges to toxicologists. The objectives of this study were (1) to develop and validate analytical methods for the determination of synthetic opioids in vitreous humor and brain, and (2) to investigate the postmortem distribution of new synthetic opioids in blood, vitreous humor, and brain tissue. Vitreous humor (0.5mL) and brain tissue (5g) homogenized in water (diluted 1:3, w/w) were extracted by mixed mode cation exchange-reversed phase solid phase extraction. Extracts were analyzed by liquid chromatography tandem mass spectrometry (LC-MSMS). The chromatographic separation was performed by reversed-phase with 0.1% formic acid in water and in acetonitrile as mobile phases in gradient mode, with a total run time of 21min. Data were acquired with ESI+ in dynamic multiple reaction mode (dMRM), monitoring 2 transitions per compound. The methods were succesfully validated following SWGTOX guidelines, with limits of quantification of 0.1ng/mL in vitreous humor and 0.1ng/g in brain. Fifty-eight authentic case samples from the New York City Office of the Chief Medical Examiner (NYC-OCME) were analyzed to assess the distribution and detectability of synthetic opioids in these postmortem samples. Of the fifteen synthetic opioids included in the method, six synthetic opioids and metabolites (4-ANPP, acetylfentanyl, fentanyl, furanylfentanyl, norfentanyl, U-47700) were detected in the authentic cases. Concentrations for most analytes were within the 0.1 to 100ng/mL or ng/g calibration range across all three matrices, with only concentrations from acetylfentanyl and U-47700 exceeding 100ng/mL or ng/g. The highest concentrations were observed in brain (except norfentanyl), followed by blood and vitreous humor. Most analytes were detected in all three matrices in a given case. This was followed by detection of an analyte in combinations of brain and another matrix or brain only. Through the case analyses, vitreous humor and brain demonstrated to be viable alternatives to blood when performing postmortem analyses of synthetic opioids. Brain exhibited a higher detectability for most analytes when compared to blood and vitreous humor.
    Mesh-Begriff(e) Analgesics, Opioid/analysis ; Analgesics, Opioid/pharmacokinetics ; Brain Chemistry ; Chromatography, Liquid ; Forensic Toxicology ; Humans ; Psychotropic Drugs/analysis ; Psychotropic Drugs/pharmacokinetics ; Solid Phase Extraction ; Synthetic Drugs/analysis ; Synthetic Drugs/pharmacokinetics ; Tandem Mass Spectrometry ; Vitreous Body/chemistry
    Chemische Substanzen Analgesics, Opioid ; Psychotropic Drugs ; Synthetic Drugs
    Sprache Englisch
    Erscheinungsdatum 2019-10-21
    Erscheinungsland Ireland
    Dokumenttyp Journal Article
    ZDB-ID 424042-x
    ISSN 1872-6283 ; 0379-0738
    ISSN (online) 1872-6283
    ISSN 0379-0738
    DOI 10.1016/j.forsciint.2019.109999
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Evaluation and applicability of Alere iCup DX 14 for rapid postmortem urine drug screening at autopsy.

    Towler, Steven / Concheiro, Marta / Pearring, Sue / Rodda, Luke N

    Journal of forensic sciences

    2020  Band 66, Heft 1, Seite(n) 375–382

    Abstract: Performing point-of-care urine drug screen testing at autopsy by a forensic pathologist may provide an early indication of the presence of analytes of interest during autopsy. An evaluation for the screening of 14 classes of common drugs of abuse in ... ...

    Abstract Performing point-of-care urine drug screen testing at autopsy by a forensic pathologist may provide an early indication of the presence of analytes of interest during autopsy. An evaluation for the screening of 14 classes of common drugs of abuse in postmortem urine by the point-of-care screening device, Alere iCup DX 14, is presented. One hundred ninety postmortem urine samples were screened with the iCup occurring at autopsy by the forensic pathologist. Positive and negative results obtained from the screening kit were evaluated against confirmatory test results obtained using routine forensic toxicology analyses that employed LC-MS/MS and GC-MS to detect a combination of over 85 common drugs of abuse and medications. Sensitivity for each respective iCup drug class ranged from 66% (buprenorphine) to 100% (methadone, tricyclic antidepressants). Specificity for each respective iCup drug class ranged from 89% (benzodiazepines) to 100% (amphetamines, barbiturates, buprenorphine, 3,4-methylenedioxymethamphetamine, methadone). Positive predictive values ranged from 44% (benzodiazepines) to 100% (amphetamines, barbiturates, buprenorphine, methylenedioxymethamphetamine, methadone), while negative predictive values ranged from 96% (methamphetamine) to 100% (barbiturates, methadone, tricyclic antidepressants). A high false-positive rate was yielded by the benzodiazepine class. The lack of fentanyl screening in the point-of-care device is a significant limitation considering its prolific prevalence in forensic casework. The results obtained in the study should be acknowledged when considering the use of the Alere iCup DX 14 in the context of postmortem casework to help indicate potential drug use contemporaneously with autopsy and when requiring such preliminary results prior to the release of a final forensic toxicology report.
    Mesh-Begriff(e) Autopsy ; Chromatography, Liquid ; Forensic Toxicology/instrumentation ; Gas Chromatography-Mass Spectrometry ; Humans ; Illicit Drugs/urine ; Pharmaceutical Preparations/urine ; Point-of-Care Systems ; Predictive Value of Tests ; Sensitivity and Specificity ; Substance Abuse Detection/instrumentation ; Tandem Mass Spectrometry
    Chemische Substanzen Illicit Drugs ; Pharmaceutical Preparations
    Sprache Englisch
    Erscheinungsdatum 2020-10-06
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 219216-0
    ISSN 1556-4029 ; 0022-1198
    ISSN (online) 1556-4029
    ISSN 0022-1198
    DOI 10.1111/1556-4029.14577
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel: Postmortem Toxicology of New Synthetic Opioids.

    Concheiro, Marta / Chesser, Rachel / Pardi, Justine / Cooper, Gail

    Frontiers in pharmacology

    2018  Band 9, Seite(n) 1210

    Abstract: One hundred fifteen Americans die every day from opioid overdose. These overdose fatalities have been augmented by the increased availability of potent synthetic opioids, such as fentanyl and its derivatives. The death rate of synthetic opioids, other ... ...

    Abstract One hundred fifteen Americans die every day from opioid overdose. These overdose fatalities have been augmented by the increased availability of potent synthetic opioids, such as fentanyl and its derivatives. The death rate of synthetic opioids, other than methadone, increased by 72.2% from 2014 to 2015, and doubled from 2015 to 2016, situating the USA in the midst of an opioid overdose epidemic. The analytical identification of these opioids in postmortem samples and the correct toxicological data interpretation is critical to identify and implement preventive strategies. This article reviews the current knowledge of postmortem toxicology of synthetic opioids and the chemical and pharmacological factors that may affect drug concentrations in the different postmortem matrices and therefore, their interpretation. These factors include key chemical properties, essential pharmacokinetics parameters (metabolism), postmortem redistribution and stability data in postmortem samples. Range and ratios of concentrations reported in traditional and non-traditional postmortem specimens, blood, urine, vitreous humor, liver and brain, are summarized in tables. The review is focused on fentanyl and derivatives (e.g., acetyl fentanyl, butyryl fentanyl, carfentanil, furanyl fentanyl, 4-methoxybutyrylfentanyl, 4-fluorobutyrylfentanyl, ocfentanil) and non-traditional opioid agonists (e.g., AH-7921, MT-45, U-47700). All of these data are critically compared to postmortem data, and chemical and pharmacological properties of natural opioids (morphine), semi-synthetic (oxycodone, hydrocodone, hydromorphone, and oxymorphone), and synthetic opioids (methadone and buprenorphine). The interpretation of drug intoxication in death investigation is based on the available published literature. This review serves to facilitate the evaluation of cases where synthetic opioids may be implicated in a fatality through the critical review of peer reviewed published case reports and research articles.
    Sprache Englisch
    Erscheinungsdatum 2018-10-26
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2018.01210
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Fast and Sensitive Method for the Determination of 17 Designer Benzodiazepines in Hair by Liquid Chromatography-Tandem Mass Spectrometry.

    DeFreitas, Laura / Fonseca Pego, Ana Miguel / Kronstrand, Robert / Lendoiro, Elena / de Castro-Ríos, Ana / Concheiro, Marta

    Journal of analytical toxicology

    2022  Band 46, Heft 8, Seite(n) 852–859

    Abstract: In recent years, identification and analysis of designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogs of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been ... ...

    Abstract In recent years, identification and analysis of designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogs of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop analytical methods to determine these compounds in different biological samples. Our aim was to develop and validate a fast, sensitive and specific method for determining 17 designer benzodiazepines (adinazolam, clobazam, clonazolam, delorazepam, deschloroetizolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam, flunitrazolam, N-desmethylclobazam, nifoxipam, nitrazolam, meclonazepam, pyrazolam and zolazepam) in hair by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Hair samples were decontaminated and pulverized, and a 20 mg aliquot was incubated in methanol in an ultrasound bath (1 h, 25°C). The supernatant was evaporated and reconstituted in 200 µL of mobile phase, and the extracts were filtered (nano-filter vials) before injection into LC-MS-MS. All analytes were eluted from the chromatographic column in 8 min, and two multiple-reaction monitoring (MRM) transitions were used to identify each compound. The limits of quantification were 5 or 25 pg/mg depending on the analyte, and the calibration functions were linear to 200 pg/mg. Imprecision was <19.2% (n = 15), and bias was from -13.7 to 18.3% (n = 15). All the analytes yielded high extraction efficiencies >70% and displayed ion suppression between -62.8% and -23.9% (n = 10). The method was applied to 19 authentic cases. Five samples were positive for flualprazolam (<LOQ-> 200 pg/mg) and/or etizolam (47.4-88.5 pg/mg). In conclusion, the present validated method has proven to be fast, sensitive, specific and capable of determining 17 designer benzodiazepines in hair using LC-MS-MS.
    Mesh-Begriff(e) Benzodiazepines/analysis ; Chromatography, Liquid/methods ; Clobazam ; Hair/chemistry ; Methanol/analysis ; Substance Abuse Detection/methods ; Tandem Mass Spectrometry/methods ; Zolazepam/analysis
    Chemische Substanzen Benzodiazepines (12794-10-4) ; Clobazam (2MRO291B4U) ; Zolazepam (G1R474U58U) ; Methanol (Y4S76JWI15)
    Sprache Englisch
    Erscheinungsdatum 2022-06-24
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 752391-9
    ISSN 1945-2403 ; 0146-4760
    ISSN (online) 1945-2403
    ISSN 0146-4760
    DOI 10.1093/jat/bkac044
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Brain Concentrations of MDPV and its Metabolites in Male Rats: Relationship to Pharmacodynamic Effects.

    Concheiro, Marta / Towler, Steven / Elmore, Joshua S / Chojnacki, Michael R / Acosta, Teeshavi / Suzuki, Masaki / Rice, Kenner C / Baumann, Michael H

    Current pharmaceutical design

    2022  Band 28, Heft 32, Seite(n) 2653–2663

    Abstract: Background: MDPV (3,4-methylenedioxypyrovalerone) is a synthetic stimulant that blocks transmitter uptake at transporters for dopamine and norepinephrine. Less is known about MDPV pharmacokinetics, especially with respect to brain concentrations of the ... ...

    Abstract Background: MDPV (3,4-methylenedioxypyrovalerone) is a synthetic stimulant that blocks transmitter uptake at transporters for dopamine and norepinephrine. Less is known about MDPV pharmacokinetics, especially with respect to brain concentrations of the drug and its metabolites.
    Objectives: The goal of the present study was: 1) to determine brain concentrations of MDPV and its metabolites, 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxy-pyrovalerone (4-OH-3-MeOPV), after administration of MDPV, and 2) to relate brain pharmacokinetic measures to pharmacodynamic endpoints in the same subjects.
    Methods: Male Sprague-Dawley rats (300-400 g) received s.c. MDPV injection (1, 2, or 4 mg/kg) or its saline vehicle. Groups of rats were decapitated at 40 min and 240 min postinjection. Locomotor behavior was rated before decapitation, and the core temperature was obtained. Plasma and frontal cortex were analyzed to quantitate MDPV and its metabolites. Striatal samples were analyzed to measure dopamine, serotonin (5-HT), and their metabolites.
    Results: MDPV displayed brain-to-plasma ratios greater than 1 (range 8.8-12.1), whereas 3,4-catechol-PV and 4-OH-3-MeO-PV showed ratios less than 1 (range 0-0.3). MDPV increased behavioural scores reflective of locomotor stimulation at 40 and 240 min and produced slight hyperthermia at 240 min. MDPV had no effect on striatal dopamine but produced an increase in the metabolite homovanillic acid (HVA). Brain MDPV concentrations were positively correlated with behavioural scores and striatal HVA but not with other endpoints.
    Conclusion: The behavioural effects of MDPV are related to brain concentrations of the parent drug and not its metabolites. The modest effects of MDPV on monoamine systems suggest that other non-monoamine mechanisms may contribute to the effects of the drug in vivo.
    Mesh-Begriff(e) Animals ; Rats ; Male ; Serotonin ; Dopamine/metabolism ; Rats, Sprague-Dawley ; Homovanillic Acid/pharmacology ; Pyrrolidines/pharmacokinetics ; Brain ; Norepinephrine ; Dose-Response Relationship, Drug
    Chemische Substanzen Serotonin (333DO1RDJY) ; Dopamine (VTD58H1Z2X) ; Homovanillic Acid (X77S6GMS36) ; Pyrrolidines ; Norepinephrine (X4W3ENH1CV)
    Sprache Englisch
    Erscheinungsdatum 2022-09-09
    Erscheinungsland United Arab Emirates
    Dokumenttyp Journal Article
    ZDB-ID 1304236-1
    ISSN 1873-4286 ; 1381-6128
    ISSN (online) 1873-4286
    ISSN 1381-6128
    DOI 10.2174/1381612828666220907100036
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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