JWH-122

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Volker Auwarter - One of the best experts on this subject based on the ideXlab platform.

  • Hair analysis for JWH-018, JWH-122, and JWH-210 after passive in vivo exposure to synthetic cannabinoid smoke
    Forensic Toxicology, 2015
    Co-Authors: Melanie Hutter, Bjoern Moosmann, Volker Auwarter, Merja A. Neukamm
    Abstract:

    Hair analysis is often used to confirm abstinence from drug use. However, interpretation of hair analysis results can be challenging, particularly with regard to smoked substances like synthetic cannabinoids, because hair can be contaminated by side-stream smoke. In this study, we measured the concentrations of synthetic cannabinoids in scalp hair after exposure to side-stream smoke from a cigarette containing the synthetic cannabinoids JWH-018, JWH-122, and JWH-210. Three participants exposed their hair to the side-stream smoke once each working day for 3 weeks to mimic realistic conditions experienced by consumers of these drugs. Two other participants exposed their hair once to the side-stream smoke of one cigarette. Scuba regulators with external air supply were used to avoid inhalation of smoke. Hair segments and wash solutions were analyzed by liquid chromatography–tandem mass spectrometry. The highest measured concentrations were 70 pg/mg of JWH-018, 260 pg/mg of JWH-122, and 950 pg/mg of JWH-210 in distal hair segments collected at the end of the exposure period. At 2–3 weeks after the end of the repeated exposure, all three synthetic cannabinoids were detected in the hair samples of both participants with longer hair. In these samples, the ratio of cannabinoid amount in acetone wash to that in hair was below 0.5 for all synthetic cannabinoids, which could be interpreted as evidence of consumption. However, with the nonconsumption of synthetic cannabinoids by our study participants being confirmed by urine testing, it is apparent that even high substance concentrations in hair samples do not prove consumption and can be explained by external contamination after contact with synthetic cannabinoids alone.

  • O23: Hair analysis for synthetic cannabinoids: How does handling of herbal mixtures during forensic analysis affect the analyst's hair concentrations?
    Toxicologie Analytique et Clinique, 2014
    Co-Authors: Volker Auwarter, Melanie Hutter, Merja A. Neukamm, Bjoern Moosmann
    Abstract:

    Introduction If narcotics police officers or other persons handling drug material at work are suspected of consuming drugs, hair analysis may be used to prove or refute such suspicion. However, it is known for many drugs that differentiation of actual drug use from external contamination can be challenging or sometimes impossible. The aim of this study was to evaluate the extent of external contamination caused by handling of synthetic cannabinoid containing drug material under realistic conditions in a forensic laboratory. Methods Hair of laboratory workers was systematically analyzed for synthetic cannabinoids with a validated LC-MS/MS method after a big seizure of legal high products had to be analyzed in our laboratory. Hair samples were taken two days after the last exposure and again one week later. In addition, hair samples of laboratory staff not directly in contact with the drug material and close relatives of exposed subjects were analyzed to check for cross contamination. Results All samples of persons who were in direct contact with drug material were tested positive for at least one of the synthetic cannabinoids (JWH-018, JWH-073, JWH-081, JWH-122, JWH-210, JWH-307, JWH-368, AM-2201, AM-2201 indazole derivative, AM- 2232, MAM-2201, RCS-4, XLR-11, 5F-PB-22, RCS-4 ortho isomer). Concentrations ranged from trace amounts up to a maximum of 170 pg/mg (JWH-210) and roughly reflected duration and intensity of exposition. There was no significant decline in concentrations from sample 1 to sample 2 (one week later). Unexpectedly, also subjects without direct contact to drug material showed measurable hair concentrations. In one case, a hair sample (21 cm) was taken 10 weeks after the last exposition with plant material. In this case, relevant concentrations of 5F-PB-22 were detected with an increase of concentrations from distal to proximal segments (7.9 – 20 pg/mg). Conclusion Depending on duration and intensity of exposition, relevant concentrations of synthetic cannabinoids may be found in hair samples of persons exposed to these drugs at work. Unexpectedly, even cross contamination from an exposed person to a close relative may occur and lead to (false) positive hair findings. Concentrations caused by contamination are in the typical range found in known users of these drugs and could lead to wrong conclusions. In contrast, detection of metabolites could strongly suggest an actual consumption. However, we did not detect such metabolites so far even in samples of known consumers of synthetic cannabinoids showing extremely high concentrations of the unchanged compounds. Therefore, body fluids have to be analyzed to unambiguously prove use of these drugs.

  • Driving under the influence of synthetic cannabinoids (“Spice”): a case series
    International Journal of Legal Medicine, 2014
    Co-Authors: Frank Musshoff, Melanie Hutter, Stefan Kneisel, Gerhard Kernbach-wighton, Wolfgang Bicker, Burkhard Madea, Volker Auwarter
    Abstract:

    Recreational use of synthetic cannabinoid receptor agonists—so-called “Spice” products—became very popular during the last few years. Several reports on clinical symptoms and poisonings were published. Unfortunately, most of these reports do not contain any analytical data on synthetic cannabinoids in body fluids, and no or only a limited number of cases were reported concerning driving under the influence (DUI) of this kind of drugs. In this article, several cases of DUI of synthetic cannabinoids (AM-2201, JWH-018, JWH-019, JWH-122, JWH-210, JWH-307, MAM-2201 (JWH-122 5-fluoropentyl derivative), and UR-144) are presented, focusing on analytical results and signs of impairment documented by the police or the physicians who had taken the blood sample from the suspects. Consumption of synthetic cannabinoids can lead to impairment similar to typical performance deficits caused by cannabis use which are not compatible with safe driving. These deficits include centrally sedating effects and impairment of fine motor skills necessary for keeping the vehicle on track. Police as well as forensic toxicologists and other groups should become familiar with the effects of synthetic cannabinoid use, and be aware of the fact that drug users may shift to these “legal” alternatives due to their nondetectability by commonly used drug screening tests based on antibodies. Sophisticated screening procedures covering the complete range of available compounds or their metabolites have to be developed for both blood/serum and urine testing.

  • P16: Hair analysis for synthetic cannabinoids: A study on the issue of passive contamination by side-stream smoke
    Toxicologie Analytique et Clinique, 2014
    Co-Authors: M. Hutter, Bjoern Moosmann, Volker Auwarter, H.c. Rudloff, Merja A. Neukamm
    Abstract:

    Introduction As hair analysis is often used for abstinence control it is crucial to consider contamination by passive exposure, particularly when drugs are smoked. In this study, the composition of main-stream and side-stream smoke of herbal mixtures containing synthetic cannabinoids was investigated and put into the context of head hair concentrations of samples collected from individuals repeatedly exposed to side-stream smoke. Methods To study the smoke composition a cigarette containing the synthetic cannabinoids JWH-018, JWH-122 and JWH-210 was smoked in a burning chamber by pulls of a piston syringe (puffvolume 35 mL/3 s, intervals 30 s). A constant air-flow of 1 L/min was applied to collect the side-stream smoke. The ethanolic solutions of main-stream and side-stream smoke condensates collected in gas wash bottles were analyzed by GC-MS. Hair contamination was studied with three volunteers who exposed their hair to the side-stream smoke of a synthetic cannabinoid cigarette five days a week during three consecutive weeks. Hair samples were obtained on a weekly basis during the exposure period and the following three weeks. Hair samples and wash solutions (water, acetone and petrol ether) were analyzed for synthetic cannabinoids by LC-MS/MS. Results Similar amounts of the synthetic cannabinoids were found in main-stream and in side-stream smoke condensates. The concentrations in hair increased with time during the exposure period (maximum concentrations were measured after the third week of exposure in a distal hair segment: 71 pg/mg JWH-018, 260 pg/mg JWH-122 and 600 pg/mg JWH-210). The concentrations decreased after the end of exposure, but most segments were still positive three weeks after the end of exposure. Regarding the washing solutions, only the acetone washings were tested positive and the analyte amounts were equal or less when compared with the amounts detected in the hair extracts. The concentration ratios of synthetic cannabinoids in hair were in good agreement with the concentration ratios in the mixture used for the exposure experiment with side-stream smoke. Conclusion Amounts of synthetic cannabinoids reaching the sidestream smoke are about as high as the amounts inhaled during smoking. Thus, hair contamination by side-stream smoke is very likely to occur and was confirmed by our smoke exposure study. The concentrations in hair after exposure are in the middle to high range compared to typical concentrations in forensic samples. Therefore, when utilizing hair analysis for abstinence control, candidates should be provided with information on the risks of external contamination. In forensic cases, utmost care has to be taken to prevent wrong conclusions when interpreting positive findings of synthetic cannabinoid in hair.

  • analysis of 30 synthetic cannabinoids in oral fluid using liquid chromatography electrospray ionization tandem mass spectrometry
    Drug Testing and Analysis, 2013
    Co-Authors: Stefan Kneisel, Jürgen Kempf, Volker Auwarter
    Abstract:

    In recent years, the analysis of synthetic cannabinoids in human specimens has gained enormous importance in the broad field of drug testing. Nevertheless, the considerable structural diversity among synthetic cannabinoids already identified in 'herbal mixtures' hampers the development of comprehensive analytical methods. As the identification of the main metabolites of newly appearing substances is very laborious and time-consuming, the detection of the parent compounds in blood samples is the current approach of choice for drug abstinence testing. Whenever blood sampling is not possible however, the need for alternative matrices arises. In this article, we present a fully validated liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the analysis of 30 synthetic cannabinoids in oral fluid samples collected with the Drager DCD 5000 collection device. The method proved to be suitable for the quantification of 28 substances. The limits of detection were in the range from 0.015 to 0.9 ng/ml, while the lower limits of quantification ranged from 0.15 to 3.0 ng/ml. The method was successfully applied to 264 authentic samples during routine analysis. A total of 31 samples (12%) was tested positive for at least one of the following synthetic cannabinoids: AM-694, AM-2201, JWH-018, JWH-019, JWH-081, JWH-122, JWH-203, JWH-210, JWH-250, JWH-307, MAM-2201, and RCS-4. Given that stabilization of the collection pads after sampling is warranted, the collection device provides satisfactory sensitivity. Hence, whenever blood sampling is not possible, the Drager DCD 5000 collection device offers a good tool for the analysis of synthetic cannabinoids in oral fluid in the broad field of drug testing. Language: en

Stefan Kneisel - One of the best experts on this subject based on the ideXlab platform.

  • Driving under the influence of synthetic cannabinoids (“Spice”): a case series
    International Journal of Legal Medicine, 2014
    Co-Authors: Frank Musshoff, Melanie Hutter, Stefan Kneisel, Gerhard Kernbach-wighton, Wolfgang Bicker, Burkhard Madea, Volker Auwarter
    Abstract:

    Recreational use of synthetic cannabinoid receptor agonists—so-called “Spice” products—became very popular during the last few years. Several reports on clinical symptoms and poisonings were published. Unfortunately, most of these reports do not contain any analytical data on synthetic cannabinoids in body fluids, and no or only a limited number of cases were reported concerning driving under the influence (DUI) of this kind of drugs. In this article, several cases of DUI of synthetic cannabinoids (AM-2201, JWH-018, JWH-019, JWH-122, JWH-210, JWH-307, MAM-2201 (JWH-122 5-fluoropentyl derivative), and UR-144) are presented, focusing on analytical results and signs of impairment documented by the police or the physicians who had taken the blood sample from the suspects. Consumption of synthetic cannabinoids can lead to impairment similar to typical performance deficits caused by cannabis use which are not compatible with safe driving. These deficits include centrally sedating effects and impairment of fine motor skills necessary for keeping the vehicle on track. Police as well as forensic toxicologists and other groups should become familiar with the effects of synthetic cannabinoid use, and be aware of the fact that drug users may shift to these “legal” alternatives due to their nondetectability by commonly used drug screening tests based on antibodies. Sophisticated screening procedures covering the complete range of available compounds or their metabolites have to be developed for both blood/serum and urine testing.

  • analysis of 30 synthetic cannabinoids in oral fluid using liquid chromatography electrospray ionization tandem mass spectrometry
    Drug Testing and Analysis, 2013
    Co-Authors: Stefan Kneisel, Jürgen Kempf, Volker Auwarter
    Abstract:

    In recent years, the analysis of synthetic cannabinoids in human specimens has gained enormous importance in the broad field of drug testing. Nevertheless, the considerable structural diversity among synthetic cannabinoids already identified in 'herbal mixtures' hampers the development of comprehensive analytical methods. As the identification of the main metabolites of newly appearing substances is very laborious and time-consuming, the detection of the parent compounds in blood samples is the current approach of choice for drug abstinence testing. Whenever blood sampling is not possible however, the need for alternative matrices arises. In this article, we present a fully validated liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the analysis of 30 synthetic cannabinoids in oral fluid samples collected with the Drager DCD 5000 collection device. The method proved to be suitable for the quantification of 28 substances. The limits of detection were in the range from 0.015 to 0.9 ng/ml, while the lower limits of quantification ranged from 0.15 to 3.0 ng/ml. The method was successfully applied to 264 authentic samples during routine analysis. A total of 31 samples (12%) was tested positive for at least one of the following synthetic cannabinoids: AM-694, AM-2201, JWH-018, JWH-019, JWH-081, JWH-122, JWH-203, JWH-210, JWH-250, JWH-307, MAM-2201, and RCS-4. Given that stabilization of the collection pads after sampling is warranted, the collection device provides satisfactory sensitivity. Hence, whenever blood sampling is not possible, the Drager DCD 5000 collection device offers a good tool for the analysis of synthetic cannabinoids in oral fluid in the broad field of drug testing. Language: en

  • Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism.
    Journal of Mass Spectrometry, 2013
    Co-Authors: Melanie Hutter, Stefan Kneisel, Volker Auwarter
    Abstract:

    Aminoalkylindoles, a subclass of synthetic cannabinoid receptor agonists, show an extensive and complex metabolism in vivo, and due to their structural similarity, they can be challenging in terms of unambiguous assignment of metabolic patterns in urine samples to consumed substances. The situation may even be more complicated as these drugs are usually smoked, and the high temperature exposure may lead to formation of artifacts. Typical metabolites of JWH-018 (Naphthalen-1-yl(1-pentyl-1H-indol-3-yl)methanone) were reportedly detected not only in urine samples collected after consumption of JWH-018 but also after AM-2201 (1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone) use. The aim of the presented study was to evaluate if typical JWH-018 metabolites can be formed metabolically in humans and if JWH-018 may be formed artifactually during smoking of AM-2201. Therefore, one of the authors ingested 5 mg of pure AM-2201, and serum as well as urine samples were analyzed subsequently. Additionally, the smoke condensate from a cigarette laced with pure AM-2201 was investigated. In addition, urine samples of patients after known consumption of AM-2201 or JWH-018 were evaluated. The results of the study prove that typical metabolites of JWH-018 and JWH-073 are built in humans after ingestion of AM-2201. However, the N-(4-hydroxypentyl) metabolite of JWH-018, which is the major metabolite after JWH-018 use, was not detected after the self-experiment. In the smoke condensate, small amounts of JWH-018 and JWH-022 (Naphthalen-1-yl[1-(pent-4-en-1-yl)-1H-indol-3-yl]methanone) were detected. Nevertheless, the results of our study suggest that the amounts absorbed by smoking do not significantly influence the metabolic pattern in urine samples. Therefore, the N-(4-hydroxypentyl) metabolite of JWH-018 can serve as a valuable marker to distinguish consume of products containing AM-2201 from JWH-018 use. Copyright © 2013 John Wiley & Sons, Ltd.

  • Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM‐2201 regarding its chemistry and metabolism
    Journal of mass spectrometry : JMS, 2013
    Co-Authors: Melanie Hutter, Stefan Kneisel, Bjoern Moosmann, Volker Auwarter
    Abstract:

    Aminoalkylindoles, a subclass of synthetic cannabinoid receptor agonists, show an extensive and complex metabolism in vivo, and due to their structural similarity, they can be challenging in terms of unambiguous assignment of metabolic patterns in urine samples to consumed substances. The situation may even be more complicated as these drugs are usually smoked, and the high temperature exposure may lead to formation of artifacts. Typical metabolites of JWH-018 (Naphthalen-1-yl(1-pentyl-1H-indol-3-yl)methanone) were reportedly detected not only in urine samples collected after consumption of JWH-018 but also after AM-2201 (1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone) use. The aim of the presented study was to evaluate if typical JWH-018 metabolites can be formed metabolically in humans and if JWH-018 may be formed artifactually during smoking of AM-2201. Therefore, one of the authors ingested 5 mg of pure AM-2201, and serum as well as urine samples were analyzed subsequently. Additionally, the smoke condensate from a cigarette laced with pure AM-2201 was investigated. In addition, urine samples of patients after known consumption of AM-2201 or JWH-018 were evaluated. The results of the study prove that typical metabolites of JWH-018 and JWH-073 are built in humans after ingestion of AM-2201. However, the N-(4-hydroxypentyl) metabolite of JWH-018, which is the major metabolite after JWH-018 use, was not detected after the self-experiment. In the smoke condensate, small amounts of JWH-018 and JWH-022 (Naphthalen-1-yl[1-(pent-4-en-1-yl)-1H-indol-3-yl]methanone) were detected. Nevertheless, the results of our study suggest that the amounts absorbed by smoking do not significantly influence the metabolic pattern in urine samples. Therefore, the N-(4-hydroxypentyl) metabolite of JWH-018 can serve as a valuable marker to distinguish consume of products containing AM-2201 from JWH-018 use. Copyright © 2013 John Wiley & Sons, Ltd.

  • acute toxicity due to the confirmed consumption of synthetic cannabinoids clinical and laboratory findings
    Addiction, 2013
    Co-Authors: Maren Hermannsclausen, Stefan Kneisel, Bela Szabo, Volker Auwarter
    Abstract:

    Aims Recently, several synthetic cannabinoids were identified in herbal mixtures consumed as recreational drugs alternative to cannabis products. The aim was to characterize the acute toxicity of synthetic cannabinoids as experienced by emergency patients. Design This was a retrospective study targeting patients seeking emergency treatment after recreational use of synthetic cannabinoids. Setting and participants Patients were selected from the database of the Poisons Information Center Freiburg between September 2008 and February 2011. The inclusion criteria were: hospitalization, available clinical reports and analytical verification of synthetic cannabinoid uptake. In total, 29 patients were included (age 14–30 years, median 19; 25 males, four females). Measurements Clinical reports were evaluated and synthetic cannabinoids and other drugs were determined analytically. Findings CP-47,497-C8 (one), JWH-015 (one), JWH-018 (eight), JWH-073 (one), JWH-081 (seven), JWH-122 (11), JWH-210 (11), JWH-250 (four) and AM 694 (one) were quantified in blood samples. JWH-018 was most common in 2008–9, JWH-122 in 2010, and JWH-210 in 2011. Tachycardia, agitation, hallucination, hypertension, minor elevation of blood glucose, hypokalaemia and vomiting were reported most frequently. Chest pain, seizures, myoclonia and acute psychosis were also noted. Conclusions There appears to have been an increase in use of the extremely potent synthetic cannabinoids JWH-122 and JWH-210. Acute toxic symptoms associated with their use are also reported after intake of high doses of cannabis, but agitation, seizures, hypertension, emesis and hypokalaemia seem to be characteristic to the synthetic cannabinoids, which are high-affinity and high-efficacy agonists of the CB1 receptor. Thus, these effects are due probably to a strong CB1 receptor stimulation.

Marilyn A Huestis - One of the best experts on this subject based on the ideXlab platform.

  • Urinary prevalence, metabolite detection rates, temporal patterns and evaluation of suitable LC-MS/MS targets to document synthetic cannabinoid intake in US military urine specimens.
    Clinical Chemistry and Laboratory Medicine, 2015
    Co-Authors: Ariane Wohlfarth, Marisol S. Castaneto, Nathalie A. Desrosiers, Thomas M. Martin, Kevin L. Klette, Karl B. Scheidweiler, Adarsh Gandhi, Marilyn A Huestis
    Abstract:

    Identifying synthetic cannabinoid designer drug abuse challenges toxicologists and drug testing programs. The best analytical approach for reliably documenting intake of emerging synthetic cannabinoids is unknown. Primarily metabolites are found in urine, but optimal metabolite targets remain unknown, and definitive identification is complicated by converging metabolic pathways. We screened 20,017 US military urine specimens collected from service members worldwide for synthetic cannabinoids between July 2011 and June 2012. We confirmed 1432 presumptive positive and 1069 presumptive negative specimens by qualitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis including 29 biomarkers for JWH-018, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, RCS-4, AM2201 and MAM2201. Specimen preparation included enzyme hydrolysis and acetonitrile precipitation prior to LC-MS/MS analysis. We evaluated individual synthetic cannabinoid metabolite detection rates, prevalence, temporal patterns and suitable targets for analytical procedures. Prevalence was 1.4% with 290 confirmed positive specimens, 92% JWH-018, 54% AM2201 and 39% JWH-122 metabolites. JWH-073, JWH-210 and JWH-250 also were identified in 37%, 4% and 8% of specimens, respectively. The United States Army Criminal Investigation Command seizure pattern for synthetic cannabinoid compounds matched our urine specimen results over the time frame of the study. Apart from one exception (AM2201), no parent compounds were observed. Hydroxyalkyl metabolites accounted for most confirmed positive tests, and in many cases, two metabolites were identified, increasing confidence in the results, and improving detection rates. These data also emphasize the need for new designer drug metabolism studies to provide relevant targets for synthetic cannabinoid identification.

  • nontargeted swath acquisition for identifying 47 synthetic cannabinoid metabolites in human urine by liquid chromatography high resolution tandem mass spectrometry
    Analytical and Bioanalytical Chemistry, 2015
    Co-Authors: Karl B. Scheidweiler, Michael Jarvis, Marilyn A Huestis
    Abstract:

    Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463–8474, [9]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599–3609, [10]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary synthetic cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 synthetic cannabinoid metabolites from 21 synthetic cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). β-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-μL mobile phase consisting of 80 % A (0.1 % formic acid in water) and 20 % B (0.1 % formic acid in acetonitrile). Fifty microliters was injected, and SWATH™ MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOF® mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25–5 μg/L (N = 10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 μg/L. Extraction efficiencies and matrix effects (N = 10) were 55–104 and −65–107 %, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 synthetic cannabinoid metabolites in human urine.

  • Nontargeted SWATH acquisition for identifying 47 synthetic cannabinoid metabolites in human urine by liquid chromatography-high-resolution tandem mass spectrometry
    Analytical and Bioanalytical Chemistry, 2015
    Co-Authors: Karl B. Scheidweiler, Michael J. Y. Jarvis, Marilyn A Huestis
    Abstract:

    Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463–8474, [ 9 ]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599–3609, [ 10 ]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary synthetic cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 synthetic cannabinoid metabolites from 21 synthetic cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). β-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-μL mobile phase consisting of 80 % A (0.1 % formic acid in water) and 20 % B (0.1 % formic acid in acetonitrile). Fifty microliters was injected, and SWATH™ MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOF® mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25–5 μg/L ( N  = 10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 μg/L. Extraction efficiencies and matrix effects ( N  = 10) were 55–104 and −65–107 %, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 synthetic cannabinoid metabolites in human urine. Graphical Abstract SWATH acquisition MS experiment

  • Urinary prevalence, metabolite detection rates, temporal patterns and evaluation of suitable LC-MS/MS targets to document synthetic cannabinoid intake in US military urine specimens
    Clinical chemistry and laboratory medicine, 2015
    Co-Authors: Ariane Wohlfarth, Marisol S. Castaneto, Nathalie A. Desrosiers, Thomas M. Martin, Kevin L. Klette, Karl B. Scheidweiler, Adarsh Gandhi, Marilyn A Huestis
    Abstract:

    Background Identifying synthetic cannabinoid designer drug abuse challenges toxicologists and drug testing programs. The best analytical approach for reliably documenting intake of emerging synthetic cannabinoids is unknown. Primarily metabolites are found in urine, but optimal metabolite targets remain unknown, and definitive identification is complicated by converging metabolic pathways. Methods We screened 20,017 US military urine specimens collected from service members worldwide for synthetic cannabinoids between July 2011 and June 2012. We confirmed 1432 presumptive positive and 1069 presumptive negative specimens by qualitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis including 29 biomarkers for JWH-018, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, RCS-4, AM2201 and MAM2201. Specimen preparation included enzyme hydrolysis and acetonitrile precipitation prior to LC-MS/MS analysis. We evaluated individual synthetic cannabinoid metabolite detection rates, prevalence, temporal patterns and suitable targets for analytical procedures. Results Prevalence was 1.4% with 290 confirmed positive specimens, 92% JWH-018, 54% AM2201 and 39% JWH-122 metabolites. JWH-073, JWH-210 and JWH-250 also were identified in 37%, 4% and 8% of specimens, respectively. The United States Army Criminal Investigation Command seizure pattern for synthetic cannabinoid compounds matched our urine specimen results over the time frame of the study. Apart from one exception (AM2201), no parent compounds were observed. Conclusions Hydroxyalkyl metabolites accounted for most confirmed positive tests, and in many cases, two metabolites were identified, increasing confidence in the results, and improving detection rates. These data also emphasize the need for new designer drug metabolism studies to provide relevant targets for synthetic cannabinoid identification.

  • Simultaneous quantification of 20 synthetic cannabinoids and 21 metabolites, and semi-quantification of 12 alkyl hydroxy metabolites in human urine by liquid chromatography-tandem mass spectrometry.
    Journal of Chromatography A, 2013
    Co-Authors: Karl B. Scheidweiler, Marilyn A Huestis
    Abstract:

    Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative efforts, complicating toxicological analysis. No extensive synthetic cannabinoid quantitative urinary methods are reported in the literature. We developed and validated a liquid chromatography tandem mass spectrometric (LC-MS/MS) method for simultaneously quantifying JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, RCS-4, AM-2201, MAM-2201, UR-144, CP 47,497-C7, CP 47,497-C8 and their metabolites, and JWH-203, AM-694, RCS-8, XLR-11 and HU-210 parent compounds in urine. Non-chromatographically resolved alkyl hydroxy metabolite isomers were considered semi-quantitative. β-glucuronidase hydrolyzed urine was extracted with 1 ml Biotage SLE+ columns. Specimens were reconstituted in 150 µL mobile phase consisting of 50% A (0.01% formic acid in water) and 50% B (0.01% formic acid in 50:50 methanol:acetonitrile). 4 and 25 µL injections were performed to acquire data in positive and negative ionization modes, respectively. The LC-MS/MS instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5500 Qtrap mass spectrometer with an electrospray source. Gradient chromatographic separation was achieved utilizing a Restek Ultra Biphenyl column with a 0.5 ml/min flow rate and an overall run time of 19.5 and 11.4 min for positive and negative mode methods, respectively. Quantification was by multiple reaction monitoring with CP 47,497 compounds and HU-210 ionized via negative polarity; all other analytes were acquired in positive mode. Lower and upper limits of linearity were 0.1–1.0 and 50–100 µg/l (r2 > 0.994). Validation parameters were evaluated at three concentrations spanning linear dynamic ranges. Inter-day analytical recovery (bias) and imprecision (N=20) were 88.3–112.2% and 4.3–13.5% coefficient of variation, respectively. Extraction efficiencies and matrix effect (N=10) were 44–110 and −73 to 52%, respectively. We present a novel LC-MS/MS method for simultaneously quantifying 20 synthetic cannabinoids and 21 metabolites, and semi-quantifying 12 alkyl hydroxy metabolites in urine.

Karl B. Scheidweiler - One of the best experts on this subject based on the ideXlab platform.

  • Urinary prevalence, metabolite detection rates, temporal patterns and evaluation of suitable LC-MS/MS targets to document synthetic cannabinoid intake in US military urine specimens.
    Clinical Chemistry and Laboratory Medicine, 2015
    Co-Authors: Ariane Wohlfarth, Marisol S. Castaneto, Nathalie A. Desrosiers, Thomas M. Martin, Kevin L. Klette, Karl B. Scheidweiler, Adarsh Gandhi, Marilyn A Huestis
    Abstract:

    Identifying synthetic cannabinoid designer drug abuse challenges toxicologists and drug testing programs. The best analytical approach for reliably documenting intake of emerging synthetic cannabinoids is unknown. Primarily metabolites are found in urine, but optimal metabolite targets remain unknown, and definitive identification is complicated by converging metabolic pathways. We screened 20,017 US military urine specimens collected from service members worldwide for synthetic cannabinoids between July 2011 and June 2012. We confirmed 1432 presumptive positive and 1069 presumptive negative specimens by qualitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis including 29 biomarkers for JWH-018, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, RCS-4, AM2201 and MAM2201. Specimen preparation included enzyme hydrolysis and acetonitrile precipitation prior to LC-MS/MS analysis. We evaluated individual synthetic cannabinoid metabolite detection rates, prevalence, temporal patterns and suitable targets for analytical procedures. Prevalence was 1.4% with 290 confirmed positive specimens, 92% JWH-018, 54% AM2201 and 39% JWH-122 metabolites. JWH-073, JWH-210 and JWH-250 also were identified in 37%, 4% and 8% of specimens, respectively. The United States Army Criminal Investigation Command seizure pattern for synthetic cannabinoid compounds matched our urine specimen results over the time frame of the study. Apart from one exception (AM2201), no parent compounds were observed. Hydroxyalkyl metabolites accounted for most confirmed positive tests, and in many cases, two metabolites were identified, increasing confidence in the results, and improving detection rates. These data also emphasize the need for new designer drug metabolism studies to provide relevant targets for synthetic cannabinoid identification.

  • nontargeted swath acquisition for identifying 47 synthetic cannabinoid metabolites in human urine by liquid chromatography high resolution tandem mass spectrometry
    Analytical and Bioanalytical Chemistry, 2015
    Co-Authors: Karl B. Scheidweiler, Michael Jarvis, Marilyn A Huestis
    Abstract:

    Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463–8474, [9]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599–3609, [10]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary synthetic cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 synthetic cannabinoid metabolites from 21 synthetic cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). β-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-μL mobile phase consisting of 80 % A (0.1 % formic acid in water) and 20 % B (0.1 % formic acid in acetonitrile). Fifty microliters was injected, and SWATH™ MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOF® mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25–5 μg/L (N = 10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 μg/L. Extraction efficiencies and matrix effects (N = 10) were 55–104 and −65–107 %, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 synthetic cannabinoid metabolites in human urine.

  • Nontargeted SWATH acquisition for identifying 47 synthetic cannabinoid metabolites in human urine by liquid chromatography-high-resolution tandem mass spectrometry
    Analytical and Bioanalytical Chemistry, 2015
    Co-Authors: Karl B. Scheidweiler, Michael J. Y. Jarvis, Marilyn A Huestis
    Abstract:

    Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463–8474, [ 9 ]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599–3609, [ 10 ]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary synthetic cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 synthetic cannabinoid metabolites from 21 synthetic cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). β-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-μL mobile phase consisting of 80 % A (0.1 % formic acid in water) and 20 % B (0.1 % formic acid in acetonitrile). Fifty microliters was injected, and SWATH™ MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOF® mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25–5 μg/L ( N  = 10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 μg/L. Extraction efficiencies and matrix effects ( N  = 10) were 55–104 and −65–107 %, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 synthetic cannabinoid metabolites in human urine. Graphical Abstract SWATH acquisition MS experiment

  • Urinary prevalence, metabolite detection rates, temporal patterns and evaluation of suitable LC-MS/MS targets to document synthetic cannabinoid intake in US military urine specimens
    Clinical chemistry and laboratory medicine, 2015
    Co-Authors: Ariane Wohlfarth, Marisol S. Castaneto, Nathalie A. Desrosiers, Thomas M. Martin, Kevin L. Klette, Karl B. Scheidweiler, Adarsh Gandhi, Marilyn A Huestis
    Abstract:

    Background Identifying synthetic cannabinoid designer drug abuse challenges toxicologists and drug testing programs. The best analytical approach for reliably documenting intake of emerging synthetic cannabinoids is unknown. Primarily metabolites are found in urine, but optimal metabolite targets remain unknown, and definitive identification is complicated by converging metabolic pathways. Methods We screened 20,017 US military urine specimens collected from service members worldwide for synthetic cannabinoids between July 2011 and June 2012. We confirmed 1432 presumptive positive and 1069 presumptive negative specimens by qualitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis including 29 biomarkers for JWH-018, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, RCS-4, AM2201 and MAM2201. Specimen preparation included enzyme hydrolysis and acetonitrile precipitation prior to LC-MS/MS analysis. We evaluated individual synthetic cannabinoid metabolite detection rates, prevalence, temporal patterns and suitable targets for analytical procedures. Results Prevalence was 1.4% with 290 confirmed positive specimens, 92% JWH-018, 54% AM2201 and 39% JWH-122 metabolites. JWH-073, JWH-210 and JWH-250 also were identified in 37%, 4% and 8% of specimens, respectively. The United States Army Criminal Investigation Command seizure pattern for synthetic cannabinoid compounds matched our urine specimen results over the time frame of the study. Apart from one exception (AM2201), no parent compounds were observed. Conclusions Hydroxyalkyl metabolites accounted for most confirmed positive tests, and in many cases, two metabolites were identified, increasing confidence in the results, and improving detection rates. These data also emphasize the need for new designer drug metabolism studies to provide relevant targets for synthetic cannabinoid identification.

  • Simultaneous quantification of 20 synthetic cannabinoids and 21 metabolites, and semi-quantification of 12 alkyl hydroxy metabolites in human urine by liquid chromatography-tandem mass spectrometry.
    Journal of Chromatography A, 2013
    Co-Authors: Karl B. Scheidweiler, Marilyn A Huestis
    Abstract:

    Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative efforts, complicating toxicological analysis. No extensive synthetic cannabinoid quantitative urinary methods are reported in the literature. We developed and validated a liquid chromatography tandem mass spectrometric (LC-MS/MS) method for simultaneously quantifying JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, RCS-4, AM-2201, MAM-2201, UR-144, CP 47,497-C7, CP 47,497-C8 and their metabolites, and JWH-203, AM-694, RCS-8, XLR-11 and HU-210 parent compounds in urine. Non-chromatographically resolved alkyl hydroxy metabolite isomers were considered semi-quantitative. β-glucuronidase hydrolyzed urine was extracted with 1 ml Biotage SLE+ columns. Specimens were reconstituted in 150 µL mobile phase consisting of 50% A (0.01% formic acid in water) and 50% B (0.01% formic acid in 50:50 methanol:acetonitrile). 4 and 25 µL injections were performed to acquire data in positive and negative ionization modes, respectively. The LC-MS/MS instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5500 Qtrap mass spectrometer with an electrospray source. Gradient chromatographic separation was achieved utilizing a Restek Ultra Biphenyl column with a 0.5 ml/min flow rate and an overall run time of 19.5 and 11.4 min for positive and negative mode methods, respectively. Quantification was by multiple reaction monitoring with CP 47,497 compounds and HU-210 ionized via negative polarity; all other analytes were acquired in positive mode. Lower and upper limits of linearity were 0.1–1.0 and 50–100 µg/l (r2 > 0.994). Validation parameters were evaluated at three concentrations spanning linear dynamic ranges. Inter-day analytical recovery (bias) and imprecision (N=20) were 88.3–112.2% and 4.3–13.5% coefficient of variation, respectively. Extraction efficiencies and matrix effect (N=10) were 44–110 and −73 to 52%, respectively. We present a novel LC-MS/MS method for simultaneously quantifying 20 synthetic cannabinoids and 21 metabolites, and semi-quantifying 12 alkyl hydroxy metabolites in urine.

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  • analysis of 30 synthetic cannabinoids in oral fluid using liquid chromatography electrospray ionization tandem mass spectrometry
    Drug Testing and Analysis, 2013
    Co-Authors: Stefan Kneisel, Jürgen Kempf, Volker Auwarter
    Abstract:

    In recent years, the analysis of synthetic cannabinoids in human specimens has gained enormous importance in the broad field of drug testing. Nevertheless, the considerable structural diversity among synthetic cannabinoids already identified in 'herbal mixtures' hampers the development of comprehensive analytical methods. As the identification of the main metabolites of newly appearing substances is very laborious and time-consuming, the detection of the parent compounds in blood samples is the current approach of choice for drug abstinence testing. Whenever blood sampling is not possible however, the need for alternative matrices arises. In this article, we present a fully validated liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the analysis of 30 synthetic cannabinoids in oral fluid samples collected with the Drager DCD 5000 collection device. The method proved to be suitable for the quantification of 28 substances. The limits of detection were in the range from 0.015 to 0.9 ng/ml, while the lower limits of quantification ranged from 0.15 to 3.0 ng/ml. The method was successfully applied to 264 authentic samples during routine analysis. A total of 31 samples (12%) was tested positive for at least one of the following synthetic cannabinoids: AM-694, AM-2201, JWH-018, JWH-019, JWH-081, JWH-122, JWH-203, JWH-210, JWH-250, JWH-307, MAM-2201, and RCS-4. Given that stabilization of the collection pads after sampling is warranted, the collection device provides satisfactory sensitivity. Hence, whenever blood sampling is not possible, the Drager DCD 5000 collection device offers a good tool for the analysis of synthetic cannabinoids in oral fluid in the broad field of drug testing. Language: en

  • Analysis of 30 synthetic cannabinoids in oral fluid using liquid chromatography‐electrospray ionization tandem mass spectrometry
    Drug Testing and Analysis, 2012
    Co-Authors: Stefan Kneisel, Volker Auwarter, Jürgen Kempf
    Abstract:

    In recent years, the analysis of synthetic cannabinoids in human specimens has gained enormous importance in the broad field of drug testing. Nevertheless, the considerable structural diversity among synthetic cannabinoids already identified in 'herbal mixtures' hampers the development of comprehensive analytical methods. As the identification of the main metabolites of newly appearing substances is very laborious and time-consuming, the detection of the parent compounds in blood samples is the current approach of choice for drug abstinence testing. Whenever blood sampling is not possible however, the need for alternative matrices arises. In this article, we present a fully validated liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for the analysis of 30 synthetic cannabinoids in oral fluid samples collected with the Drager DCD 5000 collection device. The method proved to be suitable for the quantification of 28 substances. The limits of detection were in the range from 0.015 to 0.9 ng/ml, while the lower limits of quantification ranged from 0.15 to 3.0 ng/ml. The method was successfully applied to 264 authentic samples during routine analysis. A total of 31 samples (12%) was tested positive for at least one of the following synthetic cannabinoids: AM-694, AM-2201, JWH-018, JWH-019, JWH-081, JWH-122, JWH-203, JWH-210, JWH-250, JWH-307, MAM-2201, and RCS-4. Given that stabilization of the collection pads after sampling is warranted, the collection device provides satisfactory sensitivity. Hence, whenever blood sampling is not possible, the Drager DCD 5000 collection device offers a good tool for the analysis of synthetic cannabinoids in oral fluid in the broad field of drug testing. Language: en

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