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通过液-液萃取的液相色谱法测定血浆中奥美拉唑及其两种主要代谢物来研究CYP2C19和CYP3A4的表型。

Phenotype of CYP2C19 and CYP3A4 by determination of omeprazole and its two main metabolites in plasma using liquid chromatography with liquid-liquid extraction.

作者信息

González Héctor M, Romero Elba M, Chavez Teresa de J, Peregrina A Aaron, Quezada Víctor, Hoyo-Vadillo Carlos

机构信息

Laboratories de Investigación y Desarrollo Farmacéutico, Departamento de Farmacobiología, Universidad de Guadalajara, 44840 Guadalajara, Jal, Mexico.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 25;780(2):459-65. doi: 10.1016/s1570-0232(02)00573-1.

DOI:10.1016/s1570-0232(02)00573-1
PMID:12401374
Abstract

We present a new simple and reliable HPLC method for measuring omeprazole and its two main metabolites in plasma. This can be used for studying CYP2C19 and CYP3A4 genetic polymorphisms using omeprazole as the probe drug. Omeprazole, hydroxyomeprazole and omeprazole sulfone were extracted from plasma samples with phosphate buffer and dichloromethane-ether (95:5). HPLC separation was achieved using an Ultrasphere ODS C(18) (Beckman) column. The mobile phase was acetonitrile-phosphate buffer (24:76, pH 8), containing nonylamine at 0.015%. Retention times were 9.5 min for omeprazole, 3.25 min for hydroxyomeprazole, 7.4 min for omeprazole sulfone and 6.27 min for internal standard (phenacetine). Detection (UV at 302 nm) of analytes was linear in the range from 96 to 864 ng/ml. This is useful for calculating metabolic index for CYP2C19 and CYP3A4 in adults and children. This method is stable, reproducible, improves resolution and has practical advantages such as low cost.

摘要

我们提出了一种用于测定血浆中奥美拉唑及其两种主要代谢物的简单可靠的高效液相色谱新方法。该方法可用于以奥美拉唑为探针药物研究CYP2C19和CYP3A4基因多态性。用磷酸盐缓冲液和二氯甲烷 - 乙醚(95:5)从血浆样品中提取奥美拉唑、羟基奥美拉唑和奥美拉唑砜。使用Ultrasphere ODS C(18)(贝克曼)柱进行高效液相色谱分离。流动相为乙腈 - 磷酸盐缓冲液(24:76,pH 8),含有0.015%的壬胺。奥美拉唑的保留时间为9.5分钟,羟基奥美拉唑为3.25分钟,奥美拉唑砜为7.4分钟,内标(非那西丁)为6.27分钟。分析物的检测(302 nm处紫外检测)在96至864 ng/ml范围内呈线性。这对于计算成人和儿童CYP2C19和CYP3A4的代谢指数很有用。该方法稳定、可重复,提高了分离度,具有成本低等实际优点。

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