目的 测定乙酰谷酰胺及其体内分解产物谷氨酸及γ-氨基丁酸的血、脑微透析的体外回收率,为乙酰谷酰胺在血液及脑内的药动学研究奠定基础。方法 采用LC-MS/MS测定血、脑微透析液中乙酰谷酰胺、谷氨酸及γ-氨基丁酸的浓度,计算探针回收率;考察不同灌流速度、不同药物浓度对探针体外正、反透析法回收率的影响。结果 3种检测成分血、脑探针的回收率均与流速成反比,与药物浓度无关,体外正、反2种透析法得到的探针回收率相近。同时,探针体外回收率在6 h内保持稳定。结论 反透析法能够作为乙酰谷酰胺体内回收率的测定方法,微透析技术能够用于乙酰谷酰胺血、脑药动学的研究。
Abstract
OBJECTIVE To determine the recovery rates of blood and brain microdialysis probes of acetylglutamine(NAG) and its decomposition products glutamic acid (Glu) and γ-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.
关键词
乙酰谷酰胺 /
微透析 /
谷氨酸 /
γ-氨基丁酸 /
液相色谱串联质谱法 /
探针回收率
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Key words
acetylglutamine /
microdialysis /
glutamic acid /
γ-aminobutyric acid /
LC-MS/MS /
probe recovery
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中图分类号：
R969.1
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脚注
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基金
国家自然科学基金项目资助(81373898);浙江省自然科学基金项目资助(LZ18H270001);浙江省卫生高层次创新人才培养工程项目资助(2014)
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