Simultaneous assessment of serum levels and pharmacologic effects of cannabinoids on endocannabinoids and N-acylethanolamines by liquid chromatography-tandem mass spectrometry

• Verfasst von: Couttas, Timothy [VerfasserIn]
• Verfasst von: Boost, Carola [VerfasserIn]
• Verfasst von: Pahlisch, Franziska [VerfasserIn]
• Verfasst von: Sykorova, Eliska [VerfasserIn]
• Verfasst von: Leweke, Judith E. [VerfasserIn]
• Verfasst von: Köthe, Dagmar [VerfasserIn]
• Verfasst von: Endepols, Heike [VerfasserIn]
• Verfasst von: Rohleder, Cathrin [VerfasserIn]
• Verfasst von: Leweke, F. Markus [VerfasserIn]
• Titel: Simultaneous assessment of serum levels and pharmacologic effects of cannabinoids on endocannabinoids and N-acylethanolamines by liquid chromatography-tandem mass spectrometry
• Verf.angabe: Timothy A. Couttas, Carola Boost, Franziska Pahlisch, Eliska B. Sykorova, Judith E. Leweke, Dagmar Koethe, Heike Endepols, Cathrin Rohleder, and F. Markus Leweke
• E-Jahr: 2023
• Jahr: 9 August 2023
• Umfang: 13 S.
• Fussnoten: Im Titel ist der Buchstabe "N" bei "N-acylethanolamines" in kursiver Schrift geschrieben ; Gesehen am 18.06.2024
• Titel Quelle: Enthalten in: Cannabis and cannabinoid research
• Ort Quelle: New Rochelle, NY : Liebert, 2016
• Jahr Quelle: 2023
• Band/Heft Quelle: 8(2023), 4 vom: Aug., Seite 657-669
• ISSN Quelle: 2378-8763
• DOI: doi:10.1089/can.2021.0181
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1891403648

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.