LC-MS/MS法测定人血浆中氨氯地平浓度:改善色谱条件消除基质效应  

Quantification of amlodipine in human plasma by LC-MS/MS method: elimination of matrix effects by improving chromatographic conditions

作　　者：李丹[1] 黄建耿[1] 杨丛莲[1] 斯陆勤[1] 李高[1] 

机构地区：[1]华中科技大学同济医学院药学院,湖北武汉430030

出　　处：《药学学报》2016年第6期1004-1009,共6页Acta Pharmaceutica Sinica

摘　　要：苯磺酸氨氯地平是新型二氢吡啶类钙离子拮抗剂,对血管选择性高,主要作用于外周血管,也可扩张冠状动脉和肾动脉。该药物适用于各型高血压的治疗,也可用于稳定型心绞痛患者。A liquid chromatography-tandem mass spectrometry（LC-MS/MS） method was developed and validated for the quantification of amlodipine in human plasma. The influence of alkalizer, extraction solvent and the chromatographic conditions on the matrix effects was investigated. The stable isotope-labeled amlodipine（amlodipine-d4） was used as an internal standard. Sample preparation involved simple liquid-liquid extraction procedure using methyl tertiary butyl ether. Chromatographic separation was achieved on a Welch Ultimate XB-C18（100 mm × 2.1 mm, 3 μm） column with acetonitrile/2 mmol·L^（-1） ammonium formate（p H 3.0） under gradient condition at a flow rate of 0.6 m L·min-1. Detection was performed using electrospray ionization（ESI） in positive ion multiple reaction monitoring（MRM） mode. The linear range of the analyte was 0.1-20.0 μg·L^（-1）, with the lower limit of quantitation（LLOQ） of 0.1 μg·L^（-1）. The matrix factor for low, medium, high concentration quality control samples and internal standard was（93.9 ± 1.8） %,（95.8 ± 4.9） %,（93.9 ± 1.5） % and（97.9 ± 5.3） %, respectively. The method showed excellent specificity, linearity, intra-day and inter-day accuracy and precision, extraction recovery and stability, according to the CFDA guidance for bioanalytical method validation. The matrix effect was significantly improved through optimizing the chromatographic conditions. This economical, simple, robust, sensitive and specific method is entirely able to meet the requirement of the determination of amlodipine in human plasma samples obtained from bioequivalence studies.

关 键 词：LC-MS/MS 氨氯地平 基质效应 生物等效性 

分 类 号：R917[医药卫生—药物分析学]