摘要
目的建立高效液相色谱法（HPLC）测定人血浆中吡非尼酮浓度的方法。方法采用内标法进行定量测定,含吡非尼酮血浆样品经冰醋酸酸化,加入乙酸乙酯进行提取。色谱柱为Agilent Zorbax SB-C18（4.6mm×150mm,5μm）;流动相为水-乙腈-三氟乙酸-三乙胺（72∶28∶0.1∶0.15）;流速1.0mL·min-1,柱温30℃,检测波长314 nm。12名健康受试者单次口服吡非尼酮胶囊200mg,应用HPLC测定血浆吡非尼酮浓度,计算药动学参数。结果吡非尼酮在0.05~25.00mg·L-1内线性关系良好（r=0.9999）,定量限为0.05mg·L-1。高、中、低浓度（25.00,5.00,0.10mg·L-1）的日内及日间RSD均≤8.56%,平均方法回收率分别为104.00%,103.28%和99.66%,平均提取回收率均〉70%。人体药动学研究表明,口服吡非尼酮胶囊后吸收和消除迅速,其人体药动学特征符合一级吸收的一室模型。结论该法操作简便、快速、灵敏、准确,可满足临床药动学研究的需要。
OBJECTIVE To establish a reversed phase HPLC method for the determination of pirfenidone（PF） in human plasma.METHODS PF and the internal standard were extracted from human plasma with ethyl acetate after being treated by 2% acetic acid,and then detected on an Agilent Zorbax SB-C18 column（4.6 mm×150 mm,5 μm）with UV detector at 314 nm.The mobile phase consisted of trifluoroacetic acid-triethylamine-acetonitrile-water（0.1∶0.15∶28∶72） with a flow rate of 1.0 mL·min-1.The plasma PF concentrations in 12 healthy volunteers after oral administration of PF 200 mg were determined by a validated RP-HPLC method.The pharmacokinetic parameters were calculated with DAS software.RESULTS The method was validated and found to be linear over the concentration range from 0.05 to 25.00 mg·L-1（r=0.999 9）.The limit of quantitation（LOQ） was 0.05 mg·L-1.The intra-and inter-assay coefficients of variation（CV%） for the three quality control samples（0.10,5.00,and 25.00 mg·L-1） were ≤8.56%.The mean analytical recoveries were below 104.00%,103.28% and 99.66%,respectively.The mean extraction recoveries were below 70%.The results showed the concentration-time curve of PF was discribed by a one-compartment model with first order kinetics.CONCLUSION The method is simple,rapid,sensitive and accurate,which is suitable for the pharmacokinetic study of PF in humans.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2011年第2期138-141,共4页
Chinese Pharmaceutical Journal
