Li Xiaobing, Shi Fuguo, He Xiaojing, Jian Lingyan, Ding Li
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, 563099, China.
J Pharm Biomed Anal. 2016 Sep 5;128:67-72. doi: 10.1016/j.jpba.2016.05.013. Epub 2016 May 6.
A rapid and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of lercanidipine (LER) in human plasma. The plasma sample was deproteinized with methanol after addition of diazepam (internal standard, IS) and separated on a 38°C Hedera ODS-2 analytical column with a mobile phase of methanol and 5mM ammonium acetate buffer solution containing 0.1% formic acid at an isocratic flow rate of 400μL/min. The detection was performed on an API 4000 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ESI mode. Quantification was conducted by multiple reaction monitoring (MRM) of the transitions of m/z 612.2→280.2 for LER and m/z 285.1→193.1 for IS, respectively. The method exhibited high sensitivity (LLOQ of 0.015ng/mL) and good linearity over the concentration range of 0.015-8.0ng/mL. No matrix effect and carry-over effect were observed. The values on both the occasions (intra- and inter-day) were all within 15% at three concentration levels. This robust method was successfully applied in a bioequivalence study to evaluate the pharmacokinetics of LER in 59 healthy male Chinese volunteers after a single oral administration of 10mg LER.
已开发并验证了一种快速且高灵敏度的液相色谱-串联质谱（LC-MS/MS）方法，用于测定人血浆中的乐卡地平（LER）。在加入地西泮（内标，IS）后，血浆样品用甲醇进行蛋白沉淀，然后在38°C的Hedera ODS-2分析柱上分离，流动相为甲醇和含0.1%甲酸的5mM醋酸铵缓冲溶液，等度流速为400μL/min。检测在配备电喷雾电离（ESI）源的API 4000串联质谱仪上以正ESI模式进行。分别通过对LER的m/z 612.2→280.2和IS的m/z 285.1→193.1的多反应监测（MRM）进行定量。该方法具有高灵敏度（LLOQ为0.015ng/mL），在0.015 - 8.0ng/mL的浓度范围内具有良好的线性。未观察到基质效应和残留效应。在三个浓度水平下日内和日间的值均在15%以内。这种稳健的方法成功应用于一项生物等效性研究，以评估59名健康中国男性志愿者单次口服10mg LER后LER的药代动力学。
