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目的 建立 LC-MS测定人血浆中地洛他定浓度的定量方法 ,测定志愿者口服地洛他定胶囊后的血药浓度 ,并对供试制剂与参比制剂的生物等效性进行评价。方法 血浆中加入氟西汀为内标 ,碱化后经乙酸乙酯提取 ,进行 LC-MS测定。色谱柱为 Phenomenex Luna C1 8(5 μm,2 5 0 mm× 4.6mm) ,流动相为甲醇 -乙腈 -0 .0 1mol/L醋酸铵溶液 (65∶ 5∶ 3 0 ) ,流速为 1 .0 ml/min;ESI选择性正离子检测。临床实验方案采用双交差实验设计法。结果 地洛他定血浆线性范围为 0 .1～ 3 0 ng/ml,检测限为 0 .0 5 ng/ml。方法回收率大于 80 %。应用本法测定 2 0名志愿者单剂量交叉口服供试制剂与参比制剂后的血药浓度经时过程 ,测得二者的主要药代动力学参数无显著性差异 ,试验胶囊的相对生利用度为 (96.0 4± 1 1 .1 0 ) %。结论 本方法专属性强 ,灵敏度高 ,准确性好。试验胶囊和参比片剂生物等效
OBJECTIVE To establish a quantitative method for the determination of desloratadine in human plasma by LC-MS, and to determine the plasma concentration of volunteers after oral administration of desloratadine. The bioequivalence of the test preparations and reference preparations was also evaluated. Methods Fluoxetine was added to the plasma as an internal standard, basified and extracted with ethyl acetate for LC-MS determination. The chromatographic column was Phenomenex Luna C1 8 (5 μm, 250 mm × 4.6 mm) with a mobile phase of methanol-acetonitrile-0.1 mol / L ammonium acetate solution (65: 5: 30) ml / min; ESI selective positive ion detection. Clinical experimental program using double crossover experimental design. Results The linear range of loratadine ranged from 0.1 to 30 ng / ml with a detection limit of 0.05 ng / ml. Recovery rate of more than 80%. This method was used to determine the time course of blood concentration of 20 volunteers after single-dose oral administration of test preparation and reference preparation. There was no significant difference between the two main pharmacokinetic parameters. The degree of utilization is (96.0 4 ± 1 1 .1 0)%. Conclusion This method is specific, sensitive and accurate. The test capsules are bioequivalent to the reference tablets