PMID- 25863017 OWN - NLM STAT- MEDLINE DCOM- 20160210 LR - 20211203 IS - 1873-264X (Electronic) IS - 0731-7085 (Linking) VI - 111 DP - 2015 TI - Simultaneous determination of endocannabinoids in murine plasma and brain substructures by surrogate-based LC-MS/MS: Application in tumor-bearing mice. PG - 57-63 LID - S0731-7085(15)00194-6 [pii] LID - 10.1016/j.jpba.2015.03.017 [doi] AB - The endocannabinoids (eCBs), N-arachidonoylethanolamine (anandamide, AEA) and 2-ararchidonylglycerol (2-AG) have been identified as main endogenous ligands for cannabinoid receptors. Developing a sensitive and robust method to determine AEA and 2-AG has been shown to be essential to understand their effects in stress regulation and the pathogenesis of affective disorders. Since eCBs are endogenous molecules, there is no true blank matrix available to construct calibration curves, thus, it has been a challenge to determine eCBs in plasma and brain matrix. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method is developed to determine the concentrations of AEA and 2-AG in murine plasma and different brain substructures (prefrontal cortex, hippocampus and hypothalamus). To overcome the endogenous interference, a "surrogate analyte" approach was adopted using stable isotope-labeled standards as surrogates of authentic analytes to generate calibration curves in biological matrix. The mobile phase, composed of formic acid 0.1% in water-acetonitrile (40:60, v/v), was optimized to separate 2-AG and its non-bioactive isomer 1-AG. The analytes were extracted with ethyl acetate/n-hexane (9:1, v/v) and separated on an Xbridge C18 (2.1 x 100 mm, 3.5 mum) column using N-Oleoylethanolamine-d2 (OEA-d2) as the internal standard. Detection was performed in multiple reaction monitoring (MRM) mode with an electrospray ionization source operated in positive ion mode. The method was applied to assess plasma and brain eCBs in tumor-bearing mice. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Gong, Yuan AU - Gong Y AD - Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Li, Xinmin AU - Li X AD - Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Kang, Lei AU - Kang L AD - Department of Pharmacy, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Xie, Ying AU - Xie Y AD - Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Rong, Zhengxing AU - Rong Z AD - Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Hao AU - Wang H AD - Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Qi, Hong AU - Qi H AD - Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: qihong@shsmu.edu.cn. FAU - Chen, Hongzhuan AU - Chen H AD - Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150326 PL - England TA - J Pharm Biomed Anal JT - Journal of pharmaceutical and biomedical analysis JID - 8309336 RN - 0 (Arachidonic Acids) RN - 0 (Endocannabinoids) RN - 0 (Glycerides) RN - 0 (Polyunsaturated Alkamides) RN - 8D239QDW64 (glyceryl 2-arachidonate) RN - UR5G69TJKH (anandamide) SB - IM MH - Animals MH - Arachidonic Acids/blood/metabolism MH - Brain/*metabolism MH - Calibration MH - Chromatography, Liquid/methods MH - Endocannabinoids/*blood/*metabolism MH - Glycerides/blood/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neoplasms/*blood/*metabolism MH - Plasma/*chemistry MH - Polyunsaturated Alkamides MH - Reproducibility of Results MH - Spectrometry, Mass, Electrospray Ionization/methods MH - Tandem Mass Spectrometry/methods OTO - NOTNLM OT - 2-AG OT - AEA OT - LC-MS/MS OT - Surrogate analyte OT - Tumor-bearing mice EDAT- 2015/04/12 06:00 MHDA- 2016/02/11 06:00 CRDT- 2015/04/12 06:00 PHST- 2015/02/05 00:00 [received] PHST- 2015/03/16 00:00 [revised] PHST- 2015/03/18 00:00 [accepted] PHST- 2015/04/12 06:00 [entrez] PHST- 2015/04/12 06:00 [pubmed] PHST- 2016/02/11 06:00 [medline] AID - S0731-7085(15)00194-6 [pii] AID - 10.1016/j.jpba.2015.03.017 [doi] PST - ppublish SO - J Pharm Biomed Anal. 2015;111:57-63. doi: 10.1016/j.jpba.2015.03.017. Epub 2015 Mar 26.