摘要
目的:建立高效液相色谱-串联质谱(HPLC-MS/MS)法测定肝功能不全患者血浆中利伐沙班浓度的方法。方法:采用Agilent SB-C18色谱柱(50 mm×2.1 mm,1.8μm);流动相:乙腈-10 mmol·L^-1醋酸铵缓冲液-冰醋酸(50∶50∶0.45);流速:0.2 ml·min^-1,柱温:20℃。质谱条件为电喷雾离子源,正离子模式检测,扫描方式为多反应离子监测(MRM)模式;内标法定量,用于定量分析的离子反应为m/z 436.1→145.1(利伐沙班),m/z 837.0/679.4(内标罗红霉素)。结果:血浆利伐沙班浓度在5~1000 ng·ml^-1范围内线性关系良好(r=0.9992)。日内和日间精密度均<7%,绝对回收率98.19%~103.47%,基质效应85.53%~104.06%。血浆样品室温放置6 h、反复冻融3次及-20℃冷冻30 d稳定性良好,样品浓度均无显著变化。应用本文所建立的方法测定了3例肝功能不全患者服用利伐沙班后的血药浓度,发现餐后服用和空腹服用利伐沙班可能会影响其吸收,而肝功能不全的严重程度可能会使利伐沙班的体内药动学存在较大差异。结论:所建方法快速简便、灵敏准确,可用于测定人血浆中利伐沙班的浓度,并可为利伐沙班在人体中的药动学研究提供方法学基础。
Objective:To establish an HPLC-MS/MS method for the determination of rivaroxaban in human plasma.Methods:An Agilent SB-C18 column(50 mm×2.1 mm,1.8μm)was used,the mobile phase was acetonitrile-10 mmol·L^-1 ammonium acetate buffer-glacial acetic acid(50∶50∶0.45),the flow rate was 0.2 ml·min^-1,and the column temperature was 20℃.The mass spectrometric conditions were electrospray ion source,positive ion mode detection and scanning multi reaction ion monitoring(MRM)mode.The internal standard method was used for the quantitative analysis,and the quantitative analysis of the ion reaction was m/z 436.1→145.1(rivaroxaban),and m/z 837.0/679.4(internal standard roxithromycin).Results:The linear range of rivaroxaban was 5-1000 ng·ml^-1(r=0.9992).Both the inter-and intra-day RSDs were less than 7%,the absolute recovery was 98.19%-103.47%,and the matrix effect was 85.53%-104.06%.The spiked plasma samples were stable at-20℃in a long-term stability test,after three freeze-thaw cycles and 6 h after extraction,and the changes in the concentration of rivaroxaban were not obvious.The rivaroxaban plasma concentrations in three patients with liver insufficiency were determined by the established method.Taking the drug with food or not affected the absorption of rivaroxaban,and the severity of liver insufficiency was related to the differences in rivaroxaban’s pharmacokinetics.Conclusion:The method is rapid,simple,sensitive and accurate,which can be used to determine the concentration of rivaroxaban in human plasma,and provides methodological basis for the pharmacokinetic study of rivaroxaban in human.
作者
宋尧
李哲
李任
余俊先
程晟
Song Yao;Li Zhe;Li Ren;Yu Junxian;Cheng Sheng(Department of Pharmacy,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)
出处
《中国药师》
CAS
2019年第11期2134-2137,共4页
China Pharmacist
