用LC-MS/MS法同时测定新西兰大白兔皮肤和肌肉组织中洛索洛芬及其顺反代谢产物的浓度  

Simultaneous bioanalysis of loxoprofen and its metabolites cis-trans-isomer in New Zealand white rabbis skin and muscle tissue by LC-MS/MS

作　　者：周丽莹 甘乐凌 李智燕 范亚静 ZHOU Li-ying;GAN Le-ling;LI Zhi-yan;FAN Ya-jing(Pharmacology Research Department,Beijing Tide Pharmaceutical Co.Ltd.,Beijing 100176,China)

机构地区：[1]北京泰德制药股份有限公司药理研究部,北京100176

出　　处：《中国临床药理学杂志》2023年第11期1613-1617,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的该研究建立新西兰大白兔皮肤和肌肉组织中洛索洛芬、反式羟基化洛索洛芬(trans-OH)和顺式羟基化洛索洛芬(cis-OH)的测定方法,并用于新西兰大白兔体内的药代动力学研究。方法该方法以氯唑沙宗为内标,用液液萃取法提取,样品提取物用LC-MS/MS进行分析。色谱柱:Thermo Accucore C30(2.1 mm×150.0 mm,2.6μm),流动相:乙腈-水(含10 mmol·L^(-1)醋酸铵和0.1%甲酸)=3∶7,流速:0.4 mL·min^(-1),柱温:40℃。电喷雾负离子模式,多反应监测(MRM)扫描模式进行数据的采集。以肌肉组织为例,方法学验证的内容包括特异性、灵敏度、精密度、准确度、稀释效应、提取回收率、基质效应、残留和稳定性。结果洛索洛芬及其trans-OH和cis-OH在2.00~400 ng·mL(-1)内具有良好的线性关系,特异性、灵敏度、稀释效应、提取回收率、精密度、准确度和稳定性均符合接受标准,且该方法不受基质效应的影响,无残留效应。结论本方法适用于测定新西兰大白兔皮肤和肌肉组织中洛索洛芬及其trans-OH和cis-OH的药代动力学研究。Objective To develop a LC-MS/MS method for simultaneous determination of loxoprofen and its metabolites cis-trans isomers in New Zealand white rabbit skin and muscle tissue samples and successfully apply the method to pharmacokinetic study in New Zealand white rabbit.Methods Chlorzoxazone was taken as the internal standard,and sample preparation was achieved by liquid-liquid extraction.The chromatographic separation was performed on a Thermo Accucore C30(2.1 mm×150.0 mm,2.6μm)with the mobile phase:Acetonitrile-water(containing 10 mmol·L^(-1) ammonium acetate and 0.1%formic acid)=3∶7,flow rate:0.4 mL·min^(-1),column temperature:40℃.Detection was carried out under the multiple reaction monitoring(MRM)in negative ionization mode.The present paper takes muscle tissue as an example to illustrate the method validation procedure.The proposed method was validated for selectivity,sensitivity,precision,accuracy,dilution,recovery,matrix effect,carryover and stability.Results Calibration curves were all linear in the ranges of 2.00-400 ng·mL^(-1) for loxoprofen and its metabolites trans-OH and cis-OH.The accuracy and precision of intra-and inter-day,selectivity,sensitivity,dilution,recovery and stability of the method were all within the acceptable limits and no matrix effect and carryover were observed.Conclusion This method was successfully applied to pharmacokinetic study of loxoprofen and its metabolites trans-OH and cis-OH in New Zealand white rabbit skin and muscle tissue.

关 键 词：洛索洛芬 反式羟基化洛索洛芬 顺式羟基化洛索洛芬 液液萃取 液相色谱-串联质谱 药代动力学研究 

分 类 号：R971.1[医药卫生—药品]