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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},
}