基于小鼠的他达拉非体内分布与代谢规律研究

Forensic Toxicological Study on the Distribution and Metabolism of Tadalafil in Mice

摘要: 通过优化样本处理条件和仪器检测条件建立生物样本中他达拉非的LC-MS/MS检测方法，研究其在小鼠体内的分布特征与代谢规律。分布实验设置低、中、高3组给药浓度，给药2 h后取心、脑、肝、肾、肌肉5种组织检测；代谢实验设置11个时间点，监测给药后0.17~24 h血药浓度变化。结果显示：他达拉非在小鼠体内分布规律为肝脏 > 肾脏 > 心脏 > 肌肉 > 大脑，肝脏检出量最高(检出比率0.18%)，大脑最低(检出比率0.04%)；血药浓度于给药后0.33 h达峰，0.5 h后缓慢下降，24 h仍有药物残留。所建LC-MS/MS方法线性关系良好、灵敏度高、专属性强，可用于生物样本中他达拉非的定性定量检测。本研究可为他达拉非相关中毒案件的法医学鉴定、检材选取与摄入量推断提供实验数据支撑。

Abstract: An LC-MS/MS method for the determination of tadalafil in biological samples was established by optimizing sample preparation and instrumental detection conditions, and applied to investigate its distribution characteristics and metabolic profiles in mice. For the tissue distribution study, three dose groups (low, medium, and high) were set, and five tissues including heart, brain, liver, kidney, and muscle were collected at 2 h after administration for analysis. For the pharmacokinetic study, 11 time points were designed to monitor plasma concentrations from 0.17 to 24 h post-dosing. The results showed that the tissue distribution pattern of tadalafil in mice was as follows: liver > kidney > heart > muscle > brain. The highest detection ratio was found in the liver (0.18%), while the lowest was in the brain (0.04%). The plasma concentration peaked at 0.33 h after administration, decreased slowly after 0.5 h, and drug residues were still detectable at 24 h. The established LC-MS/MS method exhibited good linearity, high sensitivity and strong specificity, which can be used for the qualitative and quantitative determination of tadalafil in biological samples. This study can provide experimental data support for forensic identification, sample selection and intake estimation in cases related to tadalafil poisoning.