摘要
目的：建立生物样本中长春瑞滨的LC—MS测定方法，研究长春瑞滨大鼠体内的药动学过程。方法：生物样本经乙酸乙酯萃取后，用LC—MS法测定长春瑞滨浓度。色谱柱为Shimadzu ODS（150mm×2．0mm，5μm），以梯度洗脱方式进行色谱分离，流速为0．2mL／min，采用电啧雾（ESI）离子源以正离子方式检测。大鼠尾静脉注射长春瑞滨乳剂，剂量为2．0、4．0和8．0mg／kg，采用DAS2．0计算药动学参数。结果：内源性杂质不干扰长春瑞滨的测定，且未出现明显的基质效应；线性范围为0．01～5．0μg／mL（r=0．9994），回收率大于90％，最低检测限为0．002μg／mL（S／N〉3）；精密度及准确度均符合生物样本测定要求。大鼠静脉注射长春瑞滨后，广泛分布于各组织中；在研究的剂量范围内，AUC与剂量间均呈良好的线性关系。结论：本实验建立的血药浓度测定方法简便、灵敏、特异，适用于大鼠血浆中长春瑞滨浓度的测定及药动学研究。
Aim： To establish an LC/MS method for the analysis of pharmacokinetics of vinorelbine in rats. Methods： The biological samples were extracted with acetic ether. The chromatographic conditions were as follows： Shimadzu ODS column （ 150 mm × 2.0 ram, 5 μm） was used. Linear gradient elution was employed at a flow rate of 0.2 mL/min. The LC-MS system was operated using an electrospray ionization probe in the positive ion mode. The pharmacokinetic parameters were calculated by DAS 2.0. Results： No interference was observed in blank plasma samples, and no ionization suppression effects were found in the biological samples. The linear range of vinorelbine in plasma was 0. 01-5. 0 μg/mL （ r = 0. 999 4） with a recovery more than 90% ; the lowest limit of determination （LLOD） for vinorelbine was 0. 002μg/mL. The sensitive and specific method was is suitable for vinorelbine determination in biological samples. After iv administration, vinorelbine was rapidly distributed into tissues, and the AUC increased linearly as the increasing of the dose. Conclusion： The method is accurate, stable and reliable, and can be used for the investigation of vinorelbine in pharmacokinetic research.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2008年第4期329-332,共4页
Journal of China Pharmaceutical University
基金
国家高技术研究发展计划("八六三"计划)资助项目(No.2002AA2Z3141)~~
