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反相液相色谱法测定人血浆中的氨鲁米特和N-乙酰氨鲁米特

Determination of aminoglutethimide and N-acetylaminoglutethimide in human plasma by reversed-phase liquid chromatography.

作者信息

Schanche J S, Lønning P E, Ueland P M, Kvinnsland S

出版信息

Ther Drug Monit. 1984;6(2):221-6. doi: 10.1097/00007691-198406000-00016.

DOI:10.1097/00007691-198406000-00016
PMID:6740741
Abstract

A liquid chromatography method for the determination of aminoglutethimide and N-acetylaminoglutethimide in human plasma is described. The assay involved precipitation of the plasma proteins using a mixture of acetonitrile and perchloric acid, without an extraction procedure. The supernatant was subjected to chromatography on a 3-micrometers ODS Hypersil column eluted isocratically with 11% acetonitrile in 100 mM ammonium formate buffer, pH 3.5. The absorbance was routinely recorded at 242 nm. The standard curves were linear in the range of 0.1-100 micrograms/ml, and the lower detection limit was approximately 0.1 microgram/ml for aminoglutethimide and its plasma metabolite N-acetylaminoglutethimide. The precision of the method, given as the coefficient of variation, was 3.9%. With this method, it was determined that aminoglutethimide and N-acetylaminoglutethimide were present in the plasma of patients receiving single-dose or continuous treatment with aminoglutethimide for breast cancer. No N-formylaminoglutethimide or nitroglutethimide could be demonstrated in the plasma from these patients. Interference from several drugs commonly given to patients with breast cancer was ruled out.

摘要

本文描述了一种用于测定人血浆中氨鲁米特和N-乙酰氨鲁米特的液相色谱法。该测定方法采用乙腈和高氯酸的混合物沉淀血浆蛋白,无需萃取步骤。上清液在3微米的ODS Hypersil柱上进行色谱分析,用含11%乙腈的100 mM甲酸铵缓冲液(pH 3.5)等度洗脱。通常在242 nm处记录吸光度。标准曲线在0.1 - 100微克/毫升范围内呈线性,氨鲁米特及其血浆代谢物N-乙酰氨鲁米特的最低检测限约为0.1微克/毫升。该方法的精密度以变异系数表示为3.9%。采用该方法测定了接受氨鲁米特单剂量或连续治疗乳腺癌患者血浆中氨鲁米特和N-乙酰氨鲁米特的含量。在这些患者的血浆中未检测到N-甲酰氨鲁米特或硝鲁米特。排除了几种常用于乳腺癌患者的药物的干扰。

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The influence of a graded dose schedule of aminoglutethimide on the disposition of the optical enantiomers of warfarin in patients with breast cancer.
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