液相色谱-电喷雾串联质谱法测定人血浆中班布特罗:在药代动力学研究中的应用

DETERMINATION OF BAMBUTEROL IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY-ELECTROSPRAY TANDEM MASS SPECTROMETRY: APPLICATION TO PHARMACOKINETIC STUDY

目的 建立液相色谱 串联质谱法测定人血浆中班布特罗浓度 ,研究中国受试者口服该药的动力学特点。方法 血浆样品经液 液萃取后 ,采用液相色谱 电喷雾串联质谱法以选择离子反应监测 (SRM)方式进行检测。结果班布特罗的线性范围为 0 0 5 - 4 0ng·mL- 1 ,最低定量浓度为 0 0 5ng·mL- 1 ,该法的日内及日间精密度 (RSD)小于8% ,准确度 (RE)在± 9%范围内。 18名中国健康受试者单剂量口服班布特罗 10mg后 ,主要药动学参数Tmax,Cmax,T1 2 和AUC0 -t分别为 (2 3± 1 3)h ,(3 95± 2 2 0 )ng·mL- 1 ,(11 4± 6 1)h和 (2 6 85± 11 77)ng·h·mL- 1 。结论 该法灵敏度高 ,操作简便、快速 。

AIM To develop a sensitive, specific and accurate method for quantifying bambuterol in human plasma and to study pharmacokinetics of bambuterol in male healthy Chinese. METHODS Plasma samples were prepared based on a simple liquid liquid extraction. The extracted samples were analyzed on liquid chromatography using a Zorbax SB C 18 column interfaced with a triple quadrupole tandem mass spectrometer and detected by use of selected reaction monitoring mode. RESULTS The linear calibration curves were obtained in the concentration range of 0 05-4 0 ng·mL -1 . The limit of quantification was 0 05 ng·mL -1 . The intra and inter run precision was measured to be below 7%. The inter run accuracy was less than 8% for the analyte. After an oral administration of 10 mg bambuterol hydrochloride to 18 healthy Chinese volunteers the main pharmacokinetic parameters of bambuterol were as follows: T max was (2 3±1 3) h; C max was (3 95±2 20) ng·mL -1 ; T 1/2 was (11 4±6 1) h and AUC 0-t was (26 85±11 77) ng·h·mL -1 . CONCLUSION The method is shown to be accurate, robust and convenient, and suitable for pharmacokinetic studies of bambuterol. It was found that there was marked inter individual difference in the pharmacokinetics of bambuterol in Chinese volunteers after a single oral dose, which may be attributed to the difference of activity of cholinesterase, an enzyme catalyzing bambuterol metabolism.