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SHR Neuro Cancer Cardio Lipid Metab Microb
Weiermair, T; Svehlikova, E; Magnes, C; Boulgaropoulos, B; Altendorfer-Kroath, T; Hummer, J; Eberl, A.
Implementation and validation of a UHPLC-MS/MS method for quantification of the endocannabinoids AEA and 2-AG in cerebral interstitial fluid and plasma.
J Pharm Biomed Anal. 2024; 238:115844
Doi: 10.1016/j.jpba.2023.115844
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Boulgaropoulos Beate
- Svehlikova Eva
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- Abstract:
- Endogenous endocannabinoids such as N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are involved in the patho-biochemistry of several neurological diseases and have been associated with mood-enhancing phenomena. Although they have been intensively studied in recent years, accurate and reliable quantification of these analytes in cerebral interstitial fluid (cISF) to elucidate their neuro-modulatory role is still challenging. Moreover, there is a need for an analytical method that can analyze plasma in addition to cISF and is thus able to address research questions in both preclinical and clinical studies. Aim was to implement a method for simultaneous quantification of AEA and 2-AG in cISF and plasma, to validate it by taking the requirements of the U.S. Food and Drug Administration into account, and to test its usability in three different case studies. A UHPLC-MS/MS method with preceding liquid-liquid extraction to determine AEA and 2-AG in cISF and plasma was successfully implemented, and the parameters selectivity, specificity, linearity, accuracy, precision, sensitivity, carry-over and stability met the validation criteria. The usability of the analytical method was demonstrated in an in vitro study with cerebral open flow microperfusion (cOFM), an in vivo cOFM study in rats, and a clinical study in human plasma. The developed method allowed quantification of AEA and 2-AG in the biologically relevant concentration ranges in cISF and plasma. The availability of a reliable, complementary, time-resolved dataset of endocannabinoid concentrations in both matrices can be of considerable future importance for the evaluation of drug efficacy.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Rats - administration & dosage
- Animals - administration & dosage
- Endocannabinoids - administration & dosage
- Tandem Mass Spectrometry - methods
- Chromatography, High Pressure Liquid - methods
- Extracellular Fluid - administration & dosage
- Polyunsaturated Alkamides - administration & dosage
- Plasma - administration & dosage
- Find related publications in this database (Keywords)
- Endocannabinoid
- Cerebral interstitial fluid
- Human plasma
- UHPLC-MS/MS
- Cerebral open flow microperfusion
- Method implementation
- N-arachidonoylethanolamine
- 2-arachidonoylglycerol