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一种使用整体柱测定人血浆中氯沙坦的快速高效液相色谱法。

A rapid HPLC method for the determination of losartan in human plasma using a monolithic column.

作者信息

Zarghi Afshin, Foroutan Seyyed Mohsen, Shafaati Alireza, Khoddam Arash

机构信息

Department of Pharmaceutical Chemistry, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Arzneimittelforschung. 2005;55(10):569-72. doi: 10.1055/s-0031-1296906.

Abstract

A rapid and simple high-performance liquid chromatography (HPLC) method using a monolithic column has been developed for quantification of losartan (CAS 12450-98-8) in plasma. The assay enables the measurement of losartan for therapeutic drug monitoring. The method involves a simple, one-step extraction procedure. The analytical recovery was complete. The separation was carried out in reversed-phase conditions using a Chromolith Performance (RP-18e, 100 x 4.6 mm) column with an isocratic mobile phase consisting of 0.01 mol/L disodium hydrogen phosphate buffer-acetonitrile (60:40 v/v) adjusted to pH 3.5. The wavelength was set at 254 nm. Thioridazine (CAS 50-52-2) was used as internal standard. Losartan, thioridazine and the EXP 3174, the active metabolite of losartan, appeared 3.4, 5.0 and 10.5 min post injection, respectively. The calibration curve was linear over the concentration range 5-300 ng mL(-1) with a minimum detectable limit of 2 ng mL(-1). The coefficients of variation for the inter-day and intra-day assay were found to be less than 8 %. The applicability of this method for pharmacokinetic studies in humans was demonstrated. The present assay is rapid, simple, precise, and accurate and is suitable for pharmacokinetic studies.

摘要

已开发出一种使用整体柱的快速简便的高效液相色谱(HPLC)方法,用于定量测定血浆中的氯沙坦(CAS 12450 - 98 - 8)。该测定法可用于治疗药物监测中氯沙坦的测量。该方法涉及一个简单的一步提取程序。分析回收率完全。分离在反相条件下进行,使用Chromolith Performance(RP - 18e,100×4.6 mm)柱,等度流动相由0.01 mol/L磷酸氢二钠缓冲液 - 乙腈(60:40 v/v)组成,pH调至3.5。波长设定为254 nm。硫利达嗪(CAS 50 - 52 - 2)用作内标。氯沙坦、硫利达嗪和氯沙坦的活性代谢物EXP 3174分别在进样后3.4、5.0和10.5分钟出现。校准曲线在5 - 300 ng mL(-1)浓度范围内呈线性,最低检测限为2 ng mL(-1)。日间和日内测定的变异系数均小于8%。证明了该方法在人体药代动力学研究中的适用性。本测定法快速、简便、精确且准确,适用于药代动力学研究。

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