人体血浆中西布曲明及其活性代谢产物的HPLC-MS/MS测定方法研究

采用高效液相色谱 -串级质谱 (HPLC-MS/MS)法测定人体血浆中西布曲明及其两种活性代谢产物浓度。以安定为内标 ,用乙醚提取 ,流动相为 V(甲醇 )∶ V(乙酸铵 )∶ V(甲酸 ) =85∶ 7.5∶ 7.5 ,质谱扫描方式为多反应离子监测 (MRM)。结果表明 :西布曲明及其两种活性代谢产物的平均相对回收率均在 92 .7%～1 0 3 .0 % ,日内、日间标准偏差 sr均小于± 1 5 % ,浓度在 0 .0 5～ 2 5 μg/L范围 ,线性关系良好。本方法灵敏度高 ,特异性强 ,保留时间短 ,适合于药物代谢动力学的研究

Quantitative Determination of Sibutramine and Its Two Active Metabolites in Human Plasma by HPLC-MS/MS

A sensitive and specific HPLC-MS/MS method is developed for the determination of sibutramine and its two active metabolites in human plasma. Plasma samples are extracted with ethyl ether and separated on an ALLTIMA C18 column with 5 mmol ammonium acetate-0.2% formic acid-methanol as the mobile phase. Detection is performed on a tandem mass spectrometry in multiple reaction monitoring (MRM) mode. The limits of determination quantitatively of sibutramine and its two metabolites are 0.05 μg/L. The weighted calibration curve is linear in the range of 0.05~25 μg/L. Inter- and intra-day relative standard deviation of sibutramine and its two metabolites are all within ±15% and the accuracies are within 92.7%~103.0%. The method will be applied to the pharmacokinetic study of sibutramine and its metabolites in Chinese healthy volunteers.