【作者】 周静雅； 高守红； 陈万生；

【机构】 第二军医大学长征医院药学部；

【摘要】 目的:建立一种简便、快速、灵敏、高效的LC-MS/MS方法同时测定静脉注射紫杉醇、多西紫杉醇、长春花碱、异长春花碱、培美曲塞二钠、伊立替康、卡铂、依托泊苷、环磷酰胺、异环磷酰胺、吉西他滨的肺癌病人血药浓度。方法:色谱分离所用的色谱柱为Atlantis T3-C18 column(2.1mm×100mm I.D.,3um)(waters,Ireland),流动相为乙腈-0.1%甲酸和10mM醋酸铵,采用梯度洗脱方式,流速0.25 mL/min。运用正离子化的多反应监测(MRM)模式,由三重四级杆串联质谱仪组成。血浆预处理运用waters Ostro样品前处理96孔板。结果:紫杉醇在25~2500 ng/mL,线性良好,多西紫杉醇在10~1000 ng/mL线性良好,吉西他滨、卡铂和依托泊苷在50~5000 ng/mL线性良好,培美曲塞二钠和异长春花碱在100~10000 ng/mL线性良好,伊立替康和长春花碱在10~10000 ng/mL线性良好,环磷酰胺和异环磷酰胺在1~1000 ng/mL线性良好(r~2>0.99)。平均提取回收率范围在64.5%-90.3%。结论:本法涵盖了肺癌病人的所有治疗浓度范围,可应用于药代动力学研究和药物不良反应监测,以便服务和指导临床给药方案的制订。更多还原

【Abstract】 Objective:A simple,rapid,sensitive and specific high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS) method,in plasma has been developed,optimized and validated for the simultaneously determination of paclitaxel,docetaxel,vinblastine,vinorelbine,pemetrexed disodium,irinotecan,carboplatin,etoposide,ifosfamide,cyclophosphamide,gemcitabine in plasma of cancer patients after intravenous injection of chemotherapy medicine.Method:The chromatographic separation was achieved on a Atlantis T3-C18column(2.1mmxl00 mm I.D.,3um)(Waters,Ireland) with gradient elution using a mobile phase consisting of acetonitrile-0.1%formic acid and 10 mM ammonium acetate in water,at a flow rate of 0.25 mL/min.The drugs were detected by an Agilent G6410 A triple quadrupole LC/MS system equipped with a MassHunter interface,using electrospray ionization(ESI) in positive-ion mode and quantified by multiple-reaction monitoring(MRM) mode.The pretreatment of plasma samples using a novel Ostro sample preparation 96-well plate procedure.Results:The calibration curves for paclitaxel in the ranges of 25 ng/mL-2500 ng/mL;for docetaxel in the ranges of 10ng/mL-1000 ng/mL;for gemcitabine,carboplatin,etoposide in the ranges of 50 ng/mL-5000 ng/mL;for vinorelbine and pemetrexed disodium in the range of 100 ng/mL-10000 ng/mL;for irinotecan and vinblastine in the range of10 ng/mL-10000 ng/mL;for ifosfamide and cyclophosphamide in the range of 1 ng/mL-1000 ng/mL showed good linearity(r~2>0.99).The mean recovery of all the analytes ranged from 64.5%to 90.3%.Conclusion:The results from assay validation showed that the method covers all therapeutic range and proved suitable for the determination of human plasma from cancer patients in order to service and instruct the clinical,which is rugged,precise,accurate,and well-suited,not only in pharmacokinetic studies but also in adverse drug reaction monitoring.更多还原