摘要
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。
AIM A LC MS method was established for the study of bioavailability and pharmacokinetics of descarboethoxyloratadine (DCL) in human plasma. METHODS After adding fluoxetine, the internal standard, and 0.1 mol/L NaOH 100 μl, the plasma samples were extracted with ethyl acetate and determined by LC MS. The mobile phase was CH 3OH CH 3CN 0.010 mol/L NH 4Ac (65∶5∶30,V/V). Analyses were conducted at a flow rate of 1.0 ml/min. Concentrations of DCL in 20 men plasma after oral administration of 20 mg DCL capsules and reference tablets were determined, at random by 2 way crossover design. Pharmacokinetic parameters were also estimated. RESULTS The assay exhibited a linear range from 0.1 to 30.0 ng/ml and gave a correlation of 0.9998. The test capsules were found to be bioequivalent to the reference tablets. The method was proved to be simple,sensitive and rapid.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2002年第4期308-311,共4页
Journal of China Pharmaceutical University
