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

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（250mm×4．6mm，5μm），乙腈-水（体积比50：50）为流动相，流速为1．0mL·min^-1，紫外检测波长为227nm，血浆样品经乙酸乙酯萃取。以内标法定量。结果线性范围为0．025～100．0mg·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7．5mg·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=0．16h），并且快速的消除，消除半衰期仅有1．65h，药物的平均保留时间tMR为0．52h。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. LiChrospher 100 RP-18 column （250 mm × 4.6 mm, 5μm） 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 25μg· 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.