Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
J Chromatogr B Analyt Technol Biomed Life Sci. 2020 May 15;1145:122094. doi: 10.1016/j.jchromb.2020.122094. Epub 2020 Apr 6.
This study shows the development and validation of two enantioselective LC-MS/MS methods for the determination of fexofenadine in biological matrices including the elution order determination. Plasma (200 µL) or urine (50 µL) aliquots were added to the internal standard solution [(S)-(-)-metoprolol] and extracted in the acid medium with chloroform. Resolution of the (R)-(+)- and (S)-(-)-fexofenadine enantiomers was performed in a Chirobiotic V column. The methods showed linearity at the range of 0.025-100 ng/mL plasma and 0.02-10 µg/mL urine for each fexofenadine enantiomer. These methods were applied to the maternal-fetal pharmacokinetics of fexofenadine enantiomers in plasma and urine of parturient women (n = 8) treated with a single oral 60 mg dose of racemic fexofenadine. Enantiomeric ratio in plasma (AUC) was close to 1.5, nevertheless in urine was closed to unity. The transplacental transfer was approximately 18% for both fexofenadine enantiomers. The enantioselective methods can also be useful in future clinical studies of chiral discrimination of drug transporters.
本研究开发并验证了两种用于测定生物基质中特非那定的对映体选择性 LC-MS/MS 方法，包括洗脱顺序的确定。取血浆（200 μL）或尿液（50 μL）等分试样，加入内标溶液[（S）-（-）-美托洛尔]，用酸性介质中的氯仿萃取。（R）-（+）-和（S）-（-）-特非那定对映体在 Chirobiotic V 柱上实现分离。两种方法在血浆中每个特非那定对映体的 0.025-100ng/mL 和尿液中 0.02-10μg/mL 的范围内均表现出线性。这些方法应用于接受单口服 60mg 消旋特非那定的产妇血浆和尿液中特非那定对映体的母体-胎儿药代动力学研究（n=8）。血浆中环（AUC）的对映体比值接近 1.5，而尿液中接近 1。两种特非那定对映体的胎盘转运率约为 18%。对映体选择性方法也可用于未来药物转运体手性分辨的临床研究。
