hplc msms技术在环苯扎林和来托司坦临床药代动力学研究中的应用-application of hplc msms technology in clinical pharmacokinetics study of cyclobenzaprine and ritostan.docx

AbstractClinical pharmacokinetics is a subject which studies on absorption, distribution, metabolism and excretion process after drug administration in human body. HPLC-MS/MS coheres high separating capability of HPLC and powerful qualitative capability, high sensitivity, good selectivity of MS/MS. It perfectly satisfies requirements of analytical methods on sensitivity and selectivity in clinical parcokinetic studies and is widely applied as a core analytical technology in this field.In this paper, two HPLC-MS/MS methods in quantitative determination of cyclobenzaprine and leitosteine were established, validated and successfully applied in clinical pharmacokinetic studies.The first part described quantitative determination of cyclobenzaprine in human plasma by HPLC-MS/MS and its application in bioequivalence evaluation of two cyclobenzaprine preparations. This HPLC-MS/MS method, using electrospray ionization as the interface, had good selectivity, high accuracy and precision. Its pre-processing, with a high extraction rate, was easy to process and the sensitivity of which was higher than those reported in former literature. In the cyclobenzaprine preparations bioequivalence evaluation, cyclobenzaprine concentration was determined after a random crossing oral administration in 20 healthy male subjects. The pharmacokinetic parameter was calculated by the software of DAS 2.1.1. It suggested that the two preparations of cyclobenzaprine were bioequivalent.The second part introduced a new established HPLC-MS/MS method for quantitative determination of leitosteine in human plasma. After optimization of HPLC conditions and MS/MS parameters, we established a new HPLC-MS/MS method. Compared to reported method of determining radioactive of isotope-labeled leitosteine, the new-established method was easy to process and more specific. The validation data suggested that the accuracy and precision of this method were acceptable; rate of extraction was stable and high. No matrix