人血中盐酸苯环壬酯的GC-MS/SIM定量测定

建立了血中盐酸苯环壬酯的GC-MS/SIM的定量分析方法。采用同位素标记物[²H₃]盐酸苯环壬酯为内标,以m/z138和m/z141为盐酸苯环壬酯和[²H₃]盐酸苯环壬酯的检测离子;方法线性度、回收率、相对标准偏差以及仪器的稳定性均达到定量测定的要求。其最低检测限为25pg·mL^-1血浆。该法应用于盐酸苯环壬酯Ⅰ期临床实验中的血药浓度测定,得到了准确、可靠的药代动力学和相对生物利用度数据,为盐酸苯环壬酯的新药报批提供了依据。

QUANTITATIVE ANALYSIS OF BENCYNONATE IN HUMAN PLASMA USING A DEUTERATED INTERNAL STANDARD BY GC-MS/SIM

Bencynonate is a newly developed anticholinergic drug.After a dose( 2 mg/per- son or 4mg/person)of bencynonate, the circulating concentrations are so low that therapeutic drug monitoring studies have prcviously been impossible. Radioisotope assay and radioaccepter assay had been used in rat experlments, but the detection limits of these methods Were not sensitive enough for the therapeutic drug monitoring. Further ,the two methods were unsuitable in the human,For evalua- tion of the pharmacokinetics and the relative bioavailability of bencynonate in man,a gas chromatographic─mass spectromectric method for quantitative analysis of bencynonate in human plasma was developed. Deuterdted bencynonate served as the internal standard and selected-ionmonitoring the fragments of bencynonate and internal standard permitted the quantitation ofbencynonate down to 25 pg·mL^-1 of plasma. The linearity was in the range from 25 pg·mL^-1 to 3 ng· mL^-1 of bencynonate plasma concentration. At 0.25 ng· mL^-1 level the recovery and relative stan-dard deviation of variation are 54.3%and 19.1%, respectively. Application of the method to clinic-al studies gave the results of pharmacokinctics and relative bioavailability of bencynonate in man.