液相色谱/质谱法测定人血清中特布他林及其药代动力学

DETERMINATION OF TERBUTALINE CONCENTRATION IN HUMAN SERUM BY LC MS AND STUDY OF ITS PHARMACOKINETICS

目的：测定人血清中特布他林浓度，研究中国男性健康志愿者口服该药后药代动力学规律。方法：用ＬＣＭＳ法测定特布他林浓度。流动相：２％冰乙酸—异丙醇（９８５∶１５）；色谱柱：ＳｈｉｍａｄｚｕＶＰＯＤＳ；流速：０５ｍＬ·ｍｉｎ－１；柱温：３０℃。结果：特布他林浓度在０２～２０ｎｇ·ｍＬ－１范围内线性关系良好（γ＝０９９９８）。方法的回收率高于９０％，最低浓度的日内及日间精密度分别为８２％和１２９％，最低检测限为００５ｎｇ。１０名健康志愿者单剂量口服特布他林口服液７５ｍｇ后，药代动力学行为符合二房室模型。结论：此法灵敏度高、选择性强，符合生物样品分析要求。

AIM: To determine the concentration of terbutaline in human serum and study the pharmacokinetics of terbutaline in Chinese male volunteers following a 7 5 mg oral dose. METHODS: A liquid chromatographic mass spectrometric assay has been developed for the determination of terbutaline in human serum. Mobile phase: 2% glacial acetic acid isopropanol (98 5∶1 5); chromatographic column: Shimadzu VP ODS, 5 μm, 4 6 mm×150 mm; flow rate: 0 5 mL·min -1 ; column temperature: 30℃. RESULTS: Assay linearity was obtained in the range of 0 2～20 ng·mL -1 (γ=0 9998). The recovery of terbutaline from human serum was more than 90%. The intra and inter assay relative standard deviations for the lowest concentration (0 5 ng·mL -1 ) examined were 8 2% and 12 9%, respectively. The method was utilized to determine the concentrations of terbutaline in Chinese male volunteers. The concentration time curve was fitted to a two compartment model. Its main pharmacokinetic parameters were: T max =(4 6±1 6) h, C max =(8 07±1 78) ng·mL -1 , T 1/2β =(9 83±2 21) h. CONCLUSION: The method is sensitive and specific enough to determine accurately the concentration of terbutaline in serum.