反相高效液相色谱法测定人血浆中氟伐他汀浓度及其药动学研究应用  

Determination of Fluvastatin Concentrations in Human Plasma by RP-HPLC with Fluorescence Detector and Its Application to Pharmacokinetic Study

作　　者：周权[1] 阮邹荣[1] 袁虹[1] 江波[1] 许东航[1] 

机构地区：[1]浙江大学医学院附属第二医院临床药理室,杭州310009

出　　处：《中国药学杂志》2006年第21期1651-1654,共4页Chinese Pharmaceutical Journal

摘　　要：目的 建立反相高效液相色谱法测定人血浆中氟伐他汀的浓度，以用于药动学研究。方法 采用体积分数0．2％磷酸乙腈溶液沉淀100μL血浆样品蛋白，高速离心后上清液直接进样分析。分析柱：Kromasil C18色谱柱（4．6inm×150mm，5μm）；流动相：0．02mol·L^-1磷酸二氢钾溶液-乙腈（53：47）；流速：1．2mL·min^-1；检测器：荧光检测器（激发波长305nm，发射波长390nm）。以外标法定量，进行方法学确证试验，并用于20名健康志愿者单剂量po-40mg氟伐他汀胶囊（来适可）的药动学研究。结果 本方法专属性强，内源性杂质和代谢物不干扰氟伐他汀的出峰。在2-600μg·L^-1内线性良好，相关系数r=0．999999（n=6）。定量限为2μg·L^-1。高、中、低质控样品的日内、日间RSD均小于10％，方法学回收率为95．0％～100．9％，平均提取回收率为111．4％。药-时曲线提示，氟伐他汀在中国人体内处置过程存在较大的个体差异。pmax，tmax，t1／2和AuC0-1值分别为（491．4±211．4）μg·L^-1，（0．6±0．2）h，（1．1±0．3）h和（540．2±226.5）μg·h·L^-1。结论 本测定方法稳定、操作简便、快速、准确、灵敏，可用于氟伐他汀药动学的研究。中国人群中的pmax，AUC0-1显著高于白人，而且还具有吸收更快、末端相消除更快的特点。OBJECTIVE To establish a RP-I-IPLC for the determination of fluvastatin（FV） concentrations in human plasma.METHODS Plasma samples （100μL） were deproteinized by precipitation with acetonitrile （containing 0.2% phosphoric acid）, centrifuged and the supernatant was directly injected into HPLC. Separation was achieved on a reverse phase column （Kromasil C18ODS 4.6 mm×150 mm,5μm）, with a mixture of 0.02 mol· L^-1 monobasic potassium phosphate-acetonitrile （53：47） as mobile phase. The flow rate was 1.2 mL·min^-1. The fluorescence detector was set at excitation wavelength of 274 nm and emission wavelength of 450 nm. The external standard method was used to quantify FV. The assay was validated and apphcated to phannacokinetic study of FV in 20 healthy volunteers following a single oral dose of 40 mg Lescol. RESULTS Endogenous chemicals and metabolite did not interfere with FV. The calibration curves were linear in the range of 2 - 600 μg· L^-1 （ r = 0.999 999, n = 6）, with a limit of quantitation of 2 μg·L^-1. The within-and between-day RSDs of quality-control samples at high-, medium-and low-concentrations were less than 8 %. The average method recovery was in the range of 95.0% - 100.9%. The average absolute recovery was 111.4%. The plasma concentration-time curves indicated great individual variability of FV disposition in Chinese. Major pharmacokinetic parameters included Pmax （491.4±211.4）μg·L^ -1, tmax （ 0.6 ± 0.2） h, t1/2 （ 1.1 ± 0.3 ） h and AUC0-1 （ 540.2 ± 226.5）μg·h·L^-1 .CONCLUSION The is stable, simple, rapid, accurate, sensitive and applicable for determining plasma concentrations of fluvastatin in its pharmacokinetic studies. Compared with caucasians, Chinese volunteers show higher values of pmax,AUC0-1 ,rapid absorption and terminal elimination profile.

关 键 词：氟伐他汀 高效液相色谱法 药动学 

分 类 号：R969.1[医药卫生—药理学]