van de Velde Daan, Bahmany Soma, Hitzerd Emilie, van Domburg Bart, Versmissen Jorie, Danser A H Jan, Koch Birgit C P
Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Paediatrics, Division of Neonatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Biomed Chromatogr. 2020 Mar;34(3):e4787. doi: 10.1002/bmc.4787. Epub 2020 Jan 19.
Endothelin receptor antagonists (ERAs) such as, ambrisentan, macitentan and sitaxentan are primarily used for the treatment of pulmonary arterial hypertension. Considering the rise in endothelin in pre-eclampsia, ERAs may also be useful in its treatment. To evaluate the pharmacokinetics of ERAs, a rapid ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated to determine the concentration of ambrisentan, macitentan and sitaxentan in human plasma. Plasma samples were treated with methanol to induce protein precipitation. A chromatographic separation was performed on a C column using a gradient of methanol-water containing 0.1% formic acid and 0.013% ammonium acetate and a flow rate of 0.5 ml/min. Multiple reaction monitoring was used for quantification. This method was validated in a linear range of 20.28-2028 μg/l for ambrisentan, 4.052-405.2 μg/l for macitentan and 205.4-10 270 μg/l for sitaxentan. The method was successfully validated according to US Food and Drug Administration guidelines to determine the concentrations of macitentan, ambrisentan and sitaxentan in human plasma. This method is now being used for study samples and clinical patient samples.
内皮素受体拮抗剂（ERA），如安立生坦、马西替坦和西他生坦，主要用于治疗肺动脉高压。鉴于子痫前期患者体内内皮素水平升高，ERA可能对其治疗也有用。为评估ERA的药代动力学，开发并验证了一种快速超高效液相色谱串联质谱法，用于测定人血浆中安立生坦、马西替坦和西他生坦的浓度。血浆样本用甲醇处理以诱导蛋白沉淀。在C柱上进行色谱分离，使用含0.1%甲酸和0.013%醋酸铵的甲醇-水梯度溶液，流速为0.5 ml/min。采用多反应监测进行定量分析。该方法在安立生坦20.28 - 2028μg/l、马西替坦4.052 - 405.2μg/l、西他生坦205.4 - 10270μg/l的线性范围内得到验证。根据美国食品药品监督管理局的指南，该方法成功验证可用于测定人血浆中马西替坦、安立生坦和西他生坦的浓度。此方法现正用于研究样本和临床患者样本。
