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作 者:赵小平[1] 王永升[1] 钟皎[1] 陈燕 柳晓泉[1] 王广基[1]
机构地区:[1]中国药科大学药物代谢与动力学研究中心,南京210009
出 处:《中国药科大学学报》2006年第3期242-245,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.2003AA2Z347A);江苏省药物代谢动力学重点实验室资助项目(No.BM2001201)~~
摘 要:目的:建立测定比格犬血浆中长春氟宁浓度的LC-MS方法,用于研究其在犬体内的药代动力学。方法:血浆样品中加入内标非那雄胺,0.25mol/L NaOH碱化后用乙酸乙酯提取,取上清真空挥干,流动相150μL溶解,取40μL进行LC-MS测定。色谱柱为Shimadzu VP-ODS柱(150mm×4.6mm ID,5μm);流动相为0.01mol/L乙酸铵水溶液-甲醇(20:80),流速为1mL/min。ESI选择正离子检测:长春氟宁,m/z:817.3;非那雄胺,m/z:373.2。结果:线性范围为0.025-12.5μg/mL。日内和日间的精密度均小于7.8%,方法回收率在97.0%-100.2%之间,提取回收率大于80%。结论:该方法选择性好,灵敏度高,操作简便,符合生物样品的测定要求,可应用于长春氟宁在犬体内的药代动力学研究。Aim: To develop a method for the quantification of vinflunine in Beagle dog' s plasma by LC-MS, and to examine phannacokinetic characteristics of vinflunine in Beagle dogs. Methods:After being spiked with finasteride as internal standard and alkalization by 0.25 mol/L NaOH, plasma was extracted by ethyl acetate. The organic layer was evaporated and reconstituted with mobile phase. Analysis of plasma was carried out on a Shimadzu VP-ODS column (150 mm ×4.6 mm ID, packed with 5 μm C18 silica RP particle). The mobile phase was consisted of methanol-10 mmoL/L ammonium acetate buffer (80:20) with the flow rate of 1.0 mL/min. LC-MS was performed in the selected ion monitoring (SIM) mode with target ions at m/z:817.3 for vinflunine and m/z:373.2 for finasteride. Results: Calibration plots for vinflunine related to internal standard, finasteride, were linear over the concentration range of 0.025 - 12.5 μg/mL. The variability values of intra-assay and inter-assay were both less than 7.8%. The relative recovery of vinflunine from plasma was in the range of 97.0% - 100.2%. Conclusion: The established LC-MS method is simple, accurate, sensitive and applicable for pharmacokinetie study of vinflunine in dogs.
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