中文摘要：

目的 建立高效液相色谱-串联质谱测定大鼠血浆左氧氟沙星含量的方法,并研究急进高原前后大鼠体内左氧氟沙星的药代动力学变化情况。方法 采用超快速液相色谱串联质谱（UFLC-MS/MS）法,以Gemini 3uC18柱（75mm×3mm,3μm）分离,以乙腈∶水∶甲酸（体积比55∶45∶0.1）为流动相进行洗脱,流速0.4mL/min,柱温30℃,进样10μL,电喷雾正离子电离（ESI）模式、多反应监测（multiple reaction monitoring,MRM）模式进行检测。12只大鼠被随机分为平原组与高原组（n=6）,实验前禁食12h。实验时,大鼠灌胃给予左氧氟沙星（20mg/kg）。于给药前（0h）和给药后0.25、0.5、0.75、1、1.5、2、4、6、8、12和24h,由眼眶静脉丛采血0.2mL,并采用UFLC-MS/MS法测定大鼠体内左氧氟沙星浓度。结果 左氧氟沙星的峰面积与其质量浓度在一定浓度范围内均呈良好的线性关系（r=0.999 5）,该方法线性范围为5.00~2.00×105μg/L,最低检测限为5.00μg/L。比较急进高原组与平原组大鼠体内左氧氟沙星药动学参数,发现其发生了显著变化,药时曲线下面积从（5 799.27±1 867.18）（μg·h）/L增大到（33 828.41±8 196.08）（μg·h）/L,峰浓度增大、体内平均驻留时间延长、总清除率降低,且差异均有统计学意义（均P〈0.05）。结论 急进高原后,左氧氟沙星在大鼠体内代谢过程发生明显变化,研究结果为平原和急进高原后临床合理应用左氧氟沙星提供参考依据。

英文摘要：

Objective To measure the contents of levofloxacin in rats by UFLC-MS/MS in an attempt to examine the chan ges of pharmacokinetics of levofloxacin in rats after acute ascent to high altitude. Methods The plasma concentration of levofloxacin was detected by UFLC-MS/MS. The Gemini 3u C18 column（75 mm× 3 mm,3 μm）was used for isolation,and acetoni trile-water-formic acid（volume ratio 55 ： 45： 0.1）as the mobile phase for elution. The flow rate of the mobile phase through the Gemini 3u C18 column was 0.4 mL/min,the column temperature was 30℃ and the adding sample was 10 μL. The MS/MS de tection was performed in multiple reaction monitoring mode（MRM）with positive electrospray ionization（ESI）. Twelve rats were randomly divided into plain group and high altitude group（n=6）. After fasting for 12 h,levofloxacin at 20 mg/kg was given by garage. Blood（0.2 mL）was collected from the orbital venous plexus before administration（0 h）and 0. 25,0. 5,0. 75,1,1. 5,2,4, 6,8,12 and 24 h after administration, respectively, and the levofloxacin concentrations were determined in the rat plasma by UFLC-MS/MS. Results The peak area showed a good linear relationship with levofloxacin（r=0. 999 5）in a certain concentration range. The linear range of levofloxacin was 5.00 - 2.00 × 10^5 μg/L and the limit of quantification （LQ） was 5.00 μg/ L. Pharmacokinetics of Levofloxacin was significantly different between the high altitude group and the plain group. The area under the curve increased from（5 799.27±1 867.18） （μg · h）/L in the plain group to（33 828. 41±8 196.08） （μg ·h）/L in the high altitude group. The Cmax was significantly higher and the average intracorporal residence time significantly prolonged and the total body clearance markedly lower in the high altitude group than in the plain group（P〈0.05）. Conclusion The in vivo metabolism of levofloxacin changed significantly in rats after acute ascent to high altitude,which provides references for clinical rational appli