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目的建立HPLC-MS法测定大鼠血浆中利福布汀浓度的方法,并对大鼠灌胃给药利福布汀后,研究利福布汀在大鼠体内的药动学。方法采用HPLC-MS法测定血浆中利福布汀的浓度。色谱柱:Waters Xbridge-C_(18)(100 mm×3.0mm,3.5μm),流动相:乙腈-水(含0.1%甲酸)=70:30;流速:0.4 ml·min~(-1),分析时间5 min,柱温:25℃,进样量:5μl,质谱条件:采用ESI源负离子模式,毛细管电压3500 V,干燥气流速10 L·min~(-1),雾化气压力35 psi,干燥气温度350℃。选择离子模式(SIM)下,利福布汀的监测离子为[M-H]~-m/z845.4和内标A3的监测离子为[M-H]~-m/z 509.3,碎片电压100 eV。结果利福布汀在0.15~30μg·ml~(-1)浓度范围内线性关系良好(r=0.9987);最低定量限为0.15μg·ml~(-1);低、中、高浓度的提取回收率为86.42%~95.80%;日内、日间精密度RSD均<11.5%。其药动学参数分别为:C_(max)(2.08±0.783)μg·ml~(-1)、T_(max)(2.20±1.247)h、t_(1/2)(12.58±4.909)h、CLz/F(1.15±0.098)L·h·kg~(-1)、Vz/F(20.31±7.276)L·kg~(-1)、AUC_(0-∞)(26.32±2.144)μg·h·ml~(-1)、MRT_(0-∞)(18.29±5.05)h、VRT_(0-∞)(379.94±195.84)h~2。结论该方法简便、准确、可靠,可用于测定大鼠血浆中利福布汀的浓度,并应用于其药代动力学研究。单次口服利福布汀后,药物吸收迅速,消除缓慢,能快速达到峰浓度,且能长时间维持较高浓度。
OBJECTIVE To establish a HPLC-MS method for the determination of rifabutin in rat plasma and to study the pharmacokinetics of rifabutin in rats after intragastric administration of rifabutin. Methods The concentrations of Rifabutin in plasma were determined by HPLC-MS. Column: Waters Xbridge-C 18 (100 mm × 3.0 mm, 3.5 μm) The analysis time was 5 min, the column temperature was 25 ℃, the injection volume was 5μl. The mass spectrometry conditions were as follows: ESI source negative ion mode, capillary voltage 3500 V, dry gas flow 10 L · min -1, atomization gas pressure 35 psi , The drying temperature is 350 ℃. Under selected ion mode (SIM), the monitored ions of rifabutin were [M-H] ~ -m / z845.4 and the internal standard A3 was [M-H] ~ -m / z 509.3 with a fragment voltage of 100 eV. Results The linear range of rifabutin was 0.15 ~ 30μg · ml ~ (-1) (r = 0.9987), the lowest limit of quantification was 0.15μg · ml ~ (-1) The recoveries ranged from 86.42% to 95.80%. The intra-day and inter-day RSDs were <11.5%. The pharmacokinetic parameters were as follows: C max 2.08 ± 0.783 μg · ml ~ (-1), T max (2.20 ± 1.247) h, t 1/2 (12.58 ± 4.909) h, The average values of CLz / F (1.15 ± 0.098) L · h · kg -1, Vz / F (20.31 ± 7.276) L · kg -1 and AUC 0-∞ (26.32 ± 2.144) μg · h Ml -1, MRT 0 -∞ 18.29 ± 5.05 h and VRT 0 -∞ 379.94 ± 195.84 h ~ 2. Conclusion The method is simple, accurate and reliable and can be used to determine the concentration of rifabutin in rat plasma and to be used in its pharmacokinetic study. After a single oral administration of rifabutin, the drug absorbed rapidly and slowly, reaching peak concentrations rapidly and maintaining a high concentration over a long period of time.