液-质联用法测定大鼠血浆中ZTW-41浓度  

Quantification of ZTW-41 in rat plasma by LC-MS/MS

作　　者：邓之荣 萧伟斌 赖崇发 严华成 卢浩扬[5] 关慧 温预关[5] 石磊 DENG Zhi-rong;XIAO Wei-bin;LAI Chong-fa;YAN Hua-cheng;LU Hao-yang;GUANG Hui;WEN Yu-guan;SHI Lei(College of Pharmacy,Guangdong Pharmaceutical University,Guangdong Guangzhou 510006,China;General Hospital of Southern Theatre Command of PLA,Guangdong Guangzhou 510010,China;Southern Medical University,Guangdong Guangzhou 510515,China;Center for Disease Control and Prevention of Southern Theater Command,Guangdong Guangzhou,510507,China;The Affiliated Brain Hospital of Guangzhou Medical University/Guangzhou Huiai Hospital,Guangdong Guangzhou,510370,China)

机构地区：[1]广东药科大学药学院,广东广州510006 [2]中国人民解放军南部战区总医院,广东广州510010 [3]南方医科大学,广东广州510515 [4]中国人民解放军广州军区疾控预防控制中心,广东广州510507 [5]广州医科大学附属脑科医院广州市惠爱医院,广东广州510370

出　　处：《中国医院药学杂志》2020年第9期996-1000,共5页Chinese Journal of Hospital Pharmacy

基　　金：广东省重大科技专项(编号:2013A022100035)。

摘　　要：目的:建立快速、灵敏、准确的LC-MS/MS法测定大鼠血浆中ZTW-41的浓度,并将该方法应用于ZTW-41的药动学研究。方法:以卡马西平为内标,血浆样品用甲醇沉淀蛋白后,通过ZORBAX Esplise XDB-C18色谱柱(4.6 mm×100 mm,3.5-Micron)进行分离,选择75%甲醇溶液(含5 mmol·L-1甲酸铵和0.1%甲酸)-甲醇溶液(含5 mmol·L-1甲酸铵和0.1%甲酸)作为流动相进行等度洗脱,流速为0.5 mL·min-1。通过ESI,以多反应监测模式(MRM)进行正离子检测,ZTW-41和卡马西平的MRM离子对分别为m/z 540.0→168.2和m/z 237.0→194.2;大鼠尾静脉给予ZTW-41前和给药后不同时间点采集血浆,血浆样品前处理后进行LC-MS/MS检测分析。结果:大鼠血浆中ZTW-41在10~3000 ng·mL-1浓度范围内具有良好的线性关系,R2≥0.99;定量下限和各浓度质控样品批间、批内精密度(RSD%)在5.82%以内,准确度(RE%)在-0.81%~4.87%之间。大鼠尾静脉给予20 mg·kg-1的ZTW-41后,Cmax为(244.78±46.67)ng·mL-1,t1/2为(21.17±2.08)h。结论:本研究建立的LC-MS/MS定量分析方法可快速、灵敏、准确地测定大鼠血浆中ZTW-41的浓度,并成功应用于ZTW-41的药动学研究。OBJECTIVE To establish a rapid,sensitive and accurate LC-MS/MS method for the determination of ZTW-41 in rat plasma,and to apply this method to the pharmacokinetic study of ZTW-41.METHODS ZTW-41 in rat plasma was extracted by protein precipitation using methanol and carbamazepine was used as internal standard.The analytes were separated on a ZORBAX Esplise XDB-C18 column(4.6 mm×100 mm,3.5-Micron).75%methanol solution(containing 5 mmol·L-1 ammonium formate and 0.1%formic acid)-methanol solution(containing 5 mmol·L-1 ammonium formate and 0.1%formic acid)was employed as a mobile phase with a flow rate of 0.5 mL·min-1.Mass detection was carried out using an electrospray ionization(ESI)source operating in positive mode.ZTW-41 and carbamazepine were analyzed by multiple reaction monitoring(MRM)and the ion transitions were m/z 540.0→168.2 and m/z 237.0→194.2,respectively.Blood samples were collected into heparinized centrifuge tubes by the postorbital venous plexus vein from each rat before and different time points after intravenous administration of ZTW-41.Plasma samples were pretreated and analyzed by LC-MS/MS.RESULTS ZTW-41 was determined over a linear calibration curve ranging from 10 to 3000 ng·mL-1,(R2≥0.99).The inter-and intra-assay precision(RSD%)were less than 5.82%,and the accuracy(RE%)was within the range of-0.81%-4.87%.After intravenous administration of ZTW-41 at doses of 20 mg·kg-1 to rats,the Cmax was(244.78±46.67)ng·mL-1;while the t1/2 was(21.17±2.08)h.CONCLUSION The LC-MS/MS quantitative analysis method established in this study can rapidly,sensitively and accurately determine the concentration of ZTW-41 in rat plasma and was successfully applied to the pharmacokinetic study of ZTW-41.

关 键 词：耐甲氧西林金黄色葡萄球菌 ZTW-41 LC-MS/MS 大鼠血浆浓度 药动学 

分 类 号：R927[医药卫生—药学]