大鼠血浆中非诺贝特活性代谢物含量测定及药代动力学研究

摘要

Objective To develop an HPLC method for determining the plasma drug concentration of fenofibrate active metabolite-fenofibric acid. Methods Acetonitrile precipitated protei and ketoprofen were used as the internal standard. The column was Acclaim120 C18. The mobile phase consisted of acetonitrile-0. 2% phosphoric acid solution ( 50 : 50 ) . The detection wavelength was 297 nm. Results The retention time of fenofibric acid and ketoprofen were about 9. 1 min and 19. 5 min, respectively. The standard curve was linear in the concentration range 0. 02-100. 00 μg/mL ( r=0. 999 4 ) . The recoveries were 97. 74% -104. 13%. The RSD of intra-and inter-day assays were both lower than 7% ( n=5 ) . Pretreated solution of fenofibric acid in human plasma was stable. Conclusion The bioavailability of self-made fenofibrate in rats is much higher than that of fenofibrate, which provides effective technical support for the clinical detection of fenofibrate and in vivo pharmacokinetics.%目的：建立测定非诺贝特在大鼠血浆中的活性代谢物非诺贝特酸含量的高效液相色谱（HPLC）法。方法以乙腈沉淀蛋白、酮洛芬为内标，采用Acclaim120 C18柱，流动相为乙腈－0.2%磷酸溶液（50：50），检测波长为297 nm。结果非诺贝特酸和酮洛芬保留时间为9.1，19.5 min；非诺贝特酸质量浓度在0.02~100.00μg/mL范围内与峰面积线性关系良好( r=0.9994)；提取回收率在97.74%~104.13%范围内，日内和日间精密度的 RSD均小于7%( n=5)，稳定性试验结果良好。结论自制非诺贝特制剂在大鼠体内的生物利用度远高于非诺贝特原料药，为临床非诺贝特药物检测和体内药代动力学研究提供了有效的技术支持。