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目的建立测定Beagle犬血浆中多奈哌齐的UPLC-MS/MS方法,并将其应用于盐酸多奈哌齐片在Beagle犬体内的药物动力学研究。方法采用沉淀蛋白法进行样品预处理,色谱柱为Acquity UPLC BEH C_(18)(50 mm×2.1 mm,1.7μm)柱,流动相采用乙腈(含体积分数0.3%甲酸)-水(含体积分数0.3%甲酸),梯度洗脱,以正离子扫描多反应监测(MRM)模式进行检测。结果血浆中多奈哌齐在质量浓度0.10~100.80μg·L~(-1)内线性关系良好,日内和日间精密度RSD均不超过10%,提取回收率为83.9%~88.1%,基质效应为95.5%~100.1%,多奈哌齐血浆样品在所考察的储存条件下均可保持稳定。结论该方法适用于盐酸多奈哌齐片在Beagle犬体内的药物动力学研究,国内研制的盐酸多奈哌齐片和国外参比制剂在Beagle犬体内的药物动力学行为具有一致性。
OBJECTIVE: To establish a UPLC-MS / MS method for the determination of donepezil in Beagle dogs plasma and to study the pharmacokinetics of donepezil hydrochloride tablets in Beagle dogs. Methods Precipitation protein was used to pretreat samples. The column was Acquity UPLC BEH C 18 (50 mm × 2.1 mm, 1.7 μm). The mobile phase consisted of acetonitrile (volume fraction 0.3% formic acid) - water (volume fraction 0.3% formic acid), gradient elution, positive ion scanning multiple reaction monitoring (MRM) mode for testing. Results Donepezil had a good linearity in the range of 0.10-100.80μg · L -1. The RSD of intra-day and inter-day precision was less than 10%, and the extraction recovery was 83.9% -88.1%. The matrix effect was 95.5 % To 100.1%, donepezil plasma samples remained stable under the storage conditions considered. Conclusion This method is suitable for the pharmacokinetics study of donepezil hydrochloride tablets in Beagle dogs. The pharmacokinetic behavior of donepezil hydrochloride tablets developed in China and foreign reference formulations are consistent in Beagle dogs.