Albayrak Mevlut, Atıla Alptug, Yılmazel Ucar Elif, Araz Omer, Kadıoglu Yucel
Department of Medical Laboratory Techniques, Health Services Vocational Training School, Ataturk University, Erzurum, Turkey.
Department of Analytical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
Biomed Chromatogr. 2019 May;33(5):e4502. doi: 10.1002/bmc.4502. Epub 2019 Feb 18.
Macitentan is an endothelin receptor antagonist commonly used in the treatment of pulmonary arterial hypertension (PAH). A novel, rapid, simple and sensitive UPLC-MS/MS method was developed and validated for pharmacokinetic study and the determination of macitentan in PAH patients. Macitentan and bosentan, which are used as internal standards, were detected using atmospheric pressure chemical ionization in positive ion and multiple reaction monitoring mode by monitoring the mass transitions m/z 589.1 → 203.3 and 552.6 → 311.5, respectively. Chromatographic separation was performed on a reverse-phase C18 column (5 μm, 4.6 × 150 mm) with an isocratic mobile phase, which consisted of water containing 0.2% acetic acid-acetonitrile (90:10, v/v) at a flow rate of 1 mL/min. Retention times were 1.97 and 1.72 min for macitentan and IS, respectively. The calibration curve with high correlation coefficient (0.9996) was linear in the range 1-500 ng/mL. The lower limit of quantitation and average recovery values were determined as 1 ng/mL and 89.8%, respectively. This method is the first UPLC-MS/MS method developed and validated for the determination of macitentan from human plasma. The developed analytical method was fully validated for linearity, selectivity, specificity, accuracy, precision, sensitivity, stability, matrix effect and recovery according to US Food and Drug Administration guidelines. The developed method was applied successfully for pharmacokinetic study and the determination of macitentan in PAH patients.
马昔腾坦是一种常用于治疗肺动脉高压（PAH）的内皮素受体拮抗剂。开发并验证了一种新颖、快速、简单且灵敏的超高效液相色谱-串联质谱（UPLC-MS/MS）方法，用于PAH患者的药代动力学研究及马昔腾坦的测定。马昔腾坦和用作内标的波生坦，采用大气压化学电离在正离子和多反应监测模式下进行检测，分别监测质荷比m/z 589.1→203.3和552.6→311.5的质量跃迁。色谱分离在反相C18柱（5μm，4.6×150mm）上进行，采用等度流动相，该流动相由含0.2%乙酸的水-乙腈（90:10，v/v）组成，流速为1mL/min。马昔腾坦和内标的保留时间分别为1.97和1.72分钟。相关系数高（0.9996）的校准曲线在1-500ng/mL范围内呈线性。定量下限和平均回收率分别确定为1ng/mL和89.8%。该方法是首个开发并验证用于测定人血浆中马昔腾坦的UPLC-MS/MS方法。根据美国食品药品监督管理局的指导原则，对所开发的分析方法在线性、选择性、特异性、准确性、精密度、灵敏度、稳定性、基质效应和回收率方面进行了全面验证。所开发的方法成功应用于PAH患者的药代动力学研究及马昔腾坦的测定。
