Rubio F, Miwa B J, Garland W A
J Chromatogr. 1982 Dec 10;233:157-65. doi: 10.1016/s0378-4347(00)81742-9.
A method is described for measuring midazolam, a new anesthesia induction agent and hypnotic, and its hydroxymethyl and desmethyl metabolites in human plasma. Deuterated analogues of each compound are added to plasma as internal standards. The compounds are extracted from plasma with benzene containing 20% 1,2-dichloroethane and after removal of the extracting solvent are dissolved in a solution of bis-(trimethylsilyl)acetamide and acetonitrile. An aliquot of this solution is analyzed by gas chromatography--mass spectrometry with the mass spectrometer set to monitor in the gas chromatographic effluent the M.- ions of drug, metabolites and internal standards generated by methane electron-capture negative chemical ionization. For all three compounds, the limit of quantitation is 1 ng ml-1, and the precision (relative standard deviation) at a concentration of 5 ng ml-1 is less than 6%. Measurable amounts of the hydroxymethyl, but not the desmethyl, metabolite of midazolam could be found in the plasma of humans given either an intravenous or an oral dose of midazolam maleate.
本文描述了一种测定人血浆中咪达唑仑（一种新型麻醉诱导剂和催眠药）及其羟甲基和去甲基代谢物的方法。将每种化合物的氘代类似物作为内标加入血浆中。用含20% 1,2 - 二氯乙烷的苯从血浆中提取这些化合物，去除提取溶剂后，将其溶解在双（三甲基硅基）乙酰胺和乙腈的溶液中。取该溶液的一份等分试样，用气相色谱 - 质谱联用仪进行分析，质谱仪设置为监测气相色谱流出物中由甲烷电子捕获负化学电离产生的药物、代谢物和内标的M.-离子。对于所有三种化合物，定量限为1 ng/ml，浓度为5 ng/ml时的精密度（相对标准偏差）小于6%。在静脉注射或口服马来酸咪达唑仑的人的血浆中，可以检测到咪达唑仑的羟甲基代谢物，但未检测到去甲基代谢物。
