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@ARTICLE{Couttas:1047476,
      author       = {Couttas, Timothy A. and Boost, Carola and Pahlisch,
                      Franziska and Sykorova, Eliska B. and Leweke, Judith E. and
                      Koethe, Dagmar and Endepols, Heike and Rohleder, Cathrin and
                      Leweke, F. Markus},
      title        = {{S}imultaneous {A}ssessment of {S}erum {L}evels and
                      {P}harmacologic {E}ffects of {C}annabinoids on
                      {E}ndocannabinoids and {N}-{A}cylethanolamines by {L}iquid
                      {C}hromatography–{T}andem {M}ass {S}pectrometry},
      journal      = {Cannabis and cannabinoid research},
      volume       = {8},
      number       = {4},
      issn         = {2578-5125},
      address      = {New Rochelle, NY},
      publisher    = {Liebert},
      reportid     = {FZJ-2025-04327},
      pages        = {657 - 669},
      year         = {2023},
      note         = {This work was supported by Deputy Vice-Chancellor Research
                      (DVCR) start up grant to F.M.L. from the University of
                      Sydney.},
      abstract     = {Introduction: The primary compounds of Cannabis sativa,
                      delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol
                      (CBD), inflict a direct influence on the endocannabinoid
                      system-a complex lipid signaling network with a central role
                      in neurotransmission and control of inhibitory and
                      excitatory synapses. These phytocannabinoids often interact
                      with endogenously produced endocannabinoids (eCBs), as well
                      as their structurally related N-acylethanolamines (NAEs), to
                      drive neurobiological, nociceptive, and inflammatory
                      responses. Identifying and quantifying changes in these
                      lipid neuromodulators can be challenging owing to their low
                      abundance in complex matrices. Materials and Methods: This
                      article describes a robust liquid chromatography-tandem mass
                      spectrometry (LC-MS/MS) method for the extraction and
                      quantification of the eCBs anandamide and
                      2-arachidonoylglycerol, along with their congener NAEs
                      oleoylethanolamine and palmitoylethanolamine, and
                      phytocannabinoids CBD, Δ9-THC, and
                      11-Nor-9-carboxy-Δ9-tetrahydrocannabinol, a major
                      metabolite of Δ9-THC. Our method was applied to explore
                      pharmacokinetic and pharmacodynamic effects from
                      intraperitoneal injections of Δ9-THC and CBD on circulating
                      levels of eCBs and NAEs in rodent serum. Results: Detection
                      limits ranged from low nanomolar to picomolar in
                      concentration for eCBs (0.012-0.24 pmol/mL), NAEs (0.059
                      pmol/mL), and phytocannabinoids (0.24-0.73 pmol/mL). Our
                      method displayed good linearity for calibration curves of
                      all analytes (R2>0.99) as well as acceptable accuracy and
                      precision, with quality controls not deviating $>15\%$ from
                      their nominal value. Our LC-MS/MS method reliably identified
                      changes to these endogenous lipid mediators that followed a
                      causal relationship, which was dependent on both the type of
                      phytocannabinoid administered and its pharmaceutical
                      preparation. Conclusion: We present a rapid and reliable
                      method for the simultaneous quantification of
                      phytocannabinoids, eCBs, and NAEs in serum using LC-MS/MS.
                      The accuracy and sensitivity of our assay infer it can
                      routinely monitor endogenous levels of these lipid
                      neuromodulators in serum and their response to external
                      stimuli, including cannabimimetic agents.},
      cin          = {INM-5},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1089/can.2021.0181},
      url          = {https://juser.fz-juelich.de/record/1047476},
}