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采用电子捕获气相色谱法测定血浆中7-氯-3-(4-甲基-1-哌嗪基)-4H-1,2,4-苯并噻二嗪-1,1-二氧化物(DU-717)

Determination of 7-chloro-3-(4-methyl-1-piperazinyl)-4h-1,2,4-benzothiadiazine-1,1-dioxide (DU-717) in plasma using electron-capture gas chromatography.

作者信息

Yamaguchi T, Miyamoto M, Utsui Y, Sekine Y, Hashimoto M

出版信息

J Chromatogr. 1978 Oct 11;160(1):181-90. doi: 10.1016/s0021-9673(00)91794-1.

DOI:10.1016/s0021-9673(00)91794-1
PMID:730789
Abstract

A gas chromatographic method has been developed which enables accurate determination of a new antihypertensive agent, DU-717, in plasma. DU-717 is first extracted with ethyl acetate and, after a clean-up procedure, derivatized with peracetic acid followed by diazomethane to form 2-methyl DU-717 N-oxide (direct methylation leads to mixtures). The N-oxide is then pyrolyzed to 2-methyl DU-717 on a gas chromatograph equipped with electron-capture detection. Accurate determinations are possible over a concentration range from 10 to 150 ng/ml of DU-717 in plasma at a relative standard deviation of 6.2%. The minimum detectable concentration is 1 ng/ml. Plasma levels of DU-717 in spontaneously hypertensive and normotensive rats following single oral administrations (10 mg/kg) have also been determined.

摘要

已开发出一种气相色谱法,可准确测定血浆中的新型抗高血压药物DU-717。首先用乙酸乙酯萃取DU-717,经过净化程序后,先用过氧乙酸进行衍生化,再用重氮甲烷处理,形成2-甲基DU-717 N-氧化物(直接甲基化会产生混合物)。然后在配备电子捕获检测器的气相色谱仪上将该N-氧化物热解为2-甲基DU-717。在血浆中DU-717浓度范围为10至150 ng/ml时,可进行准确测定,相对标准偏差为6.2%。最低检测浓度为1 ng/ml。还测定了自发性高血压大鼠和正常血压大鼠单次口服给药(10 mg/kg)后血浆中DU-717的水平。

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