Abstract：
This study aimed to establish a simple and sensitive analytical method to simultaneously quantify donepezil (DPZ) and tadalafil (TAD) in rat plasma using lansoprazole (LPZ) as an internal standard (IS) by using liquid chromatography tandem mass spectrometry. The fragmentation pattern of DPZ, TAD, and IS was elucidated using multiple reaction monitoring in electrospray ionization positive ion mode for the quantification of precursor to production at m/z 380.1 → 91.2 for DPZ, m/z 390.2 → 268.1 for TAD, and m/z 370.3 → 252.0 for LPZ. The extracted DPZ and TAD from plasma using acetonitrile-induced protein precipitation was separated using Kinetex C18 (100 × 2.1 mm, 2.6 µm) column with a gradient mobile phase system consisting of 2 mM ammonium acetate and 0.1% formic acid in acetonitrile at a flow rate of 0.25 mL/min for 4 min. The selectivity, lower limit of quantification, linearity, precision, accuracy, stability, recovery, and matrix effect of this developed method was validated according to the guidelines of the U.S. Food and Drug Administration and the Ministry of Food and Drug Safety of Korea. The established method achieved acceptance criteria in all validation parameters, ensuring reliability, reproducibility, and accuracy, and was successfully implemented in a pharmacokinetic study on the co-administration of DPZ and TAD orally in rats.
摘要：
本研究以兰索拉唑(LPZ)为内标(IS),建立一种简便、灵敏的同时定量大鼠血浆多奈哌齐(DPZ)和他达拉非(TAD)的液相色谱串联质谱分析方法。DPZ的碎片模式，TAD,并使用电喷雾电离正离子模式下的多反应监测来阐明IS，以量化DPZ在m/z380.1→91.2时的前体产量，对于TAD，m/z390.2→268.1，LPZ的m/z为370.3→252.0。使用乙腈诱导的蛋白沉淀从血浆中提取的DPZ和TAD使用KinetexC18（100×2.1mm，2.6µm）的色谱柱，其梯度流动相系统由2mM乙酸铵和0.1％甲酸在乙腈中以0.25mL/min的流速组成，持续4分钟。选择性,定量下限，线性度精度,准确度,稳定性,recovery,并根据美国食品和药物管理局和韩国食品药品安全部的指南验证了该方法的基质效应。所建立的方法在所有验证参数中都达到了验收标准，确保可靠性，再现性，和准确性，并在大鼠口服DPZ和TAD共同给药的药代动力学研究中成功实施。
