Asgari Arezoo, Kobarfard Farzad, Keyhanfar Fariborz, Mohebbi Shohreh, Noubarani Maryam
Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2015 Summer;14(3):739-46.
In previous studies, mebudipine, a dihydropyridine calcium channel blocker, showed a considerable potential to be used in cardiovascular diseases. The aim of the current study was to develop a valid method using reversed-phase high performance liquid chromatography coupled with electrospray ionization mass spectrometry to assay mebudipine in the human plasma. Separation was achieved on a Zorbax Eclipse(®) C18 analytical column using a mobile phase consisted of methanol/water (90:10, v/v). The flow rate was 0.6 mL/min and carbamazepine was used as an internal standard (IS). This method involved the use of M +Na ions of mebudipine and IS at m/z 411 and 259, respectively with the selected ion monitoring (SIM) mode. There were no interfering peaks from endogenous components in blank plasma chromatograms. Standard curves were linear (r(2)>0.99) between 5 to 100 ng/mL. The mean extraction efficiency was about 84% and the limit of quantification for mebudipine was 5 ng/mL in plasma. The coefficient of variation and error at all of the intra-day and inter-day assessments were less than 11%. The results indicated that this method is a fast, accurate, sensitive, selective and reliable method for the determination of mebudipine in the human plasma. The assay method has been successfully used to estimate plasma concentration of mebudipine after the oral administration of 2.5 mg tablet in healthy adults.
在先前的研究中，二氢吡啶类钙通道阻滞剂美布地尔在心血管疾病治疗方面显示出了巨大的应用潜力。本研究的目的是开发一种有效的反相高效液相色谱-电喷雾电离质谱联用方法，用于测定人血浆中的美布地尔。采用Zorbax Eclipse(®) C18分析柱进行分离，流动相为甲醇/水（90:10，v/v）。流速为0.6 mL/min，卡马西平用作内标（IS）。该方法采用选择离子监测（SIM）模式，分别监测美布地尔和内标的m/z 411和259处的M +Na离子。空白血浆色谱图中无内源性成分干扰峰。标准曲线在5至100 ng/mL之间呈线性（r(2)>0.99）。平均提取效率约为84%，血浆中美布地尔的定量限为5 ng/mL。日内和日间评估的变异系数和误差均小于11%。结果表明，该方法是一种快速、准确、灵敏、选择性好且可靠的人血浆中美布地尔测定方法。该测定方法已成功用于健康成年人口服2.5 mg片剂后美布地尔血浆浓度的估算。
