RP-HPLC法测定紫杉醇在大鼠血浆中的含量Development and validation of a method to determine paclitaxel in plasma
杨涛,崔福德,金大德
YANG Tao1,CUI Fu-de1,Dae-duk KIM2(1.School of Pharmacy
摘要(Abstract):
目的建立紫杉醇在大鼠血浆中的定量分析方法,为药物动力学研究提供分析方法。方法采用RP-HPLC法。Li Chrospher 100反相C18色谱柱(250 mm×4.6 mm,5μm),乙腈-水(体积比50∶50)为流动相,流速为1.0 mL.min-1,紫外检测波长为227 nm,血浆样品经乙酸乙酯萃取,以内标法定量。结果线性范围为0.025~100.0 mg.L-1(r=1.0,n=5),日内RSD小于5%,日间RSD小于10%,定量限25μg.L-1。在以7.5 mg.kg-1的剂量静脉注射紫杉醇到大鼠身上后,药物很快分布到体内(t1/2α=0.16 h),并且快速的消除,消除半衰期仅有1.65 h,药物的平均保留时间tMR为0.52 h。结论所用方法简便、准确、专属性好,能够满足药物动力学研究的需要。
Objective To develop a method for the determination of paclitaxel in rat plasma.Methods RP-HPLC was used to determine the concentration of paclitaxel and n-butyl p-hydroxybenzoate was used as internal standard.LiChrospherR 100 RP-18 column(250 mm×4.6 mm,5 μm) was used as analytical column and the mobile phase was composed of acetonitrile and water(V∶V=50∶50).The flow rate was 1.0 mL·min-1 and the detection wavelength was 227 nm.The rat plasma samples were extracted with ethyl acetate.Results The linearity was 0.025-100.0 mg·L-1 and the limit of quantification was 25 μg·L-1.The inter-day RSD was below 5% while the intra-day RSD was smaller than 10%.Paclitaxel was quickly removed from the circulating system after intravenous injection of paclitaxel 7.5 mg·kg-1 to rats,showing a rapid distribution phase(t1/2α=0.16 h) and a rapid terminal elimination phase(t1/2β=1.65 h).Conclusions The assay method is simple,selective,and sensitive enough for the application of preclinical pharmacokinetic study.
关键词(KeyWords):
紫杉醇;反相高效液相色谱法;血药浓度
paclitaxel;RP-HPLC;plasma concentration
基金项目(Foundation):
作者(Author):
杨涛,崔福德,金大德
YANG Tao1,CUI Fu-de1,Dae-duk KIM2(1.School of Pharmacy
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