Abstract��OBJECTIVE To determine the recovery rates of blood and brain microdialysis probes of acetylglutamine(NAG) and its decomposition products glutamic acid (Glu) and ��-aminobutyric acid (GABA) in vitro, and lay the foundation for the pharmacokinetic study of NAG in blood and brain.METHODS The concentrations of NAG, Glu and GABA in blood and brain microdialysates were determined by LC-MS/MS and the probe recoveries were calculated. The in vitro recoveries of NAG, Glu and GABA were studied using positive dialysis and retrodialysis methods at different flow rates and concentrations.RESULTS The in vitro recoveries of blood and brain probes of NAG, Glu and GABA were inversely proportional to the perfusate flow rates while independent of drug concentrations. The recovery rates obtained by positive dialysis and retrodialysis methods in vitro were approximately equal under the same condition, and were stable for at least 6 h.CONCLUSION Retrodialysis method can be used to study the probe recovery of NAG, and microdialysis can be used for blood and brain pharmacokinetic study of NAG.
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DENG Ling, WAN Hai-tong, YU Li, ZHOU Hui-fen, CHEN Jian-zhen, HE Yu. Analysis on Blood and Brain Microdialysis Probes Recovery of N-acetyl-L-glutamine, Glutamic Acid and ��-Aminobutyric Acid in Vitro Using LC-MS/MS. Chinese Pharmaceutical Journal, 2018, 53(9): 719-724.
ZHANG R, YANG N, JI C, et al. Neuroprotective effects of aceglutamide on motor function in a rat model of cerebral ischemia and reperfusion[J] . Restor Neurol Neuros, 2015, 33 (5):741-759.
[2]
YANG J J, LU S G. Effects of aceglutamide on newborn rats with hypoxic-ischemic encephalopathy[J] . Heilongjiang Med J(������ҽҩ), 2013, 126 (4):589-591.
[3]
YANG L, WANG Y, WANG Y Q, et al. N-Methyl-D-aspartate receptors subunits expression in neurons derived from rat neural stem cell[J] . Neurosci Bull (��ѧͨ��), 2005, 21(1):58-62.
[4]
CHAURASIA C S. In vivo microdialysis sampling:theory and applications[J] . Biomed Chromatogr, 1999, 13 (5):317-332.
[5]
DARVESH A S, CARROLL R T, GELDENHUYS W J, et al. In vivo brain microdialysis:advances in neuropsychopharmacology and drug discovery[J] . Expert Opin Drug Dis, 2011, 6 (2):109-127.
[6]
HOLMGAARD R, NIELSEN J B, BENFELDT E. Microdialysis sampling for investigations of bioavailability and bioequivalence of topically administered drugs:current state and future perspectives[J] . Skin Pharmacol Phys, 2010, 23 (5):225-243.
[7]
BENVENISTE H, H��TTEMEIER P C. Microdialysis--theory and application[J] . Prog Neurobiol, 1990, 35 (3):195-215.
[8]
BOURNE J A. Intracerebral microdialysis:30 years as a tool for the neuroscientist[J] . Clin Exp Pharmacol P, 2003, 30(2):16-24.
[9]
SNOWDEN M K, BAXTER J H, BERGANA M M, et al. Stability of N-acetylglutamine and glutamine in aqueous solution and in a liquid nutritional product by an improved HPLC method[J] . J Food Sci, 2002, 67(1):384-389.
[10]
XIAO J, TIAN H, LIANG J G. Determination of relevant substance in aceglutamide injection by RP-HPLC[J] . Cent South Pharm (����ҩѧ),2010, 8 (11):808-811.
[11]
SHAO R H, YUAN W. Determination of aceglutamide and related substances in aceglutamide and glucose injection by HPLC[J] . Qilu Pharm Aff(��³ҩ��), 2007, 26 (6):336-338.
[12]
ZHANG Y, HE Z F, TANG Z, et al. Microdialysis recovery of oxymatrine in vitro and in vivo[J] . Chin J Tradit Chin Med Pharm (�л���ҽҩ��־), 2015,30(9):3108-3111.
[13]
YOSHITAKE S, IJIRI S, KEHR J, et al. Inhibition of histamine release by local and intracerebroventricular infusion of galanin in hypothalamus, hippocampus and prefrontal cortex of awake rat: a microdialysis study[J] . Neurosci Lett, 2013, 534 (1):58-63.
[14]
PRETTI L, BAZZU G, SERRA P A, et al. A novel method for the determination of ascorbic acid and antioxidant capacity in Opuntia ficus indica, using in vivo, microdialysis[J] . Food Chem, 2014, 147 (6):131-137.
[15]
ROGERS M L, BRENNAN P A, LEONG C L, et al. Online rapid sampling microdialysis (rsMD) using enzyme-based electroanalysis for dynamic detection of ischaemia during free flap reconstructive surgery[J] . Anal Bioanal Chem, 2013, 405(11):3881-3888.
[16]
JIANG Y Y, YE G M, WANG D. In vitro and in vivo microdialysis recovery of berberine hydrochloride[J] . Chin J Pharm Anal (ҩ�������־), 2016,7 (36):1184-1189.
[17]
DE LANGE E C,DE BOER A G, BREIMER D D. Methodological issues in microdialysis sampling for pharmacokinetic studies[J] . Adv Drug Deliv Rev, 2000, 45(2):125-148.
[18]
THOLANCE Y, BARCELOS G, QUADRIO I, et al. Analytical validation of microdialysis analyzer for monitoring glucose, lactate and pyruvate in cerebral microdialysates[J] . Clin Chim Acta, 2011, 412 (7-8):647-654.
[19]
STENKEN J A. Methods and issues in microdialysis calibration[J] . Anal Chim Acta, 1999, 379 (3):337-358.
[20]
ZHANG Y, HE Z F, TANG Z, et al. In vitro and in vivo microdialysis recovery of matrine[J] . Chin Pharm J(�й�ҩѧ��־), 2014, 49 (22):2031-2035.
[21]
SHI Z Y, HU X, CHEN X H, et al. Study on brain pharmacokinetics of S-ornidazole after oral administration in rats by microdialysis[J] . Chin Pharm J (�й�ҩѧ��־), 2011, 46(21):1661-1664.
[22]
CHEN T F, LIU J X, ZHANG Y, et al. Analysis on microdialysis probe recovery of baicalin in vitro and in vivo based on LC-MS/MS[J] . China J Chin Mater Med (�й���ҩ��־), 2017, 42(11):2168-2174.
2018, Vol. 53 
