摘要
目的:采用高效液相色谱法测定大鼠血浆中黄体酮的浓度,以用于黄体酮脂质纳米粒的药动学研究。方法:大鼠血样用乙酸乙酯提取,采用达那唑为内标,以HypersilC18柱(150mm×3.9mm,5μm)为分析柱,甲醇:水(60:40)为流动相,流速0.6ml/min,检测波长为240nm。以去势大鼠为模型动物,应用建立的方法,测定大鼠口服黄体酮脂质纳米粒后的血浆药物浓度。结果:黄体酮在0.02~2μg/ml浓度范围内线性关系良好(r=0.9999,n=3),定量限为(0.02±0.004)μg/ml(n=3),最低检测线为0.005μg/ml(S/N≥3)。高、中、低质控样品的日内、日间RSD均小于10%,平均提取回收率为90.5%,方法学回收率为93.4%~107.5%。血药浓度-时间曲线提示,脂质纳米粒延缓药物的达峰时间,并明显提高药物的生物利用度。结论:本测定方法稳定,操作简便、快速、准确、灵敏,可用于黄体酮脂质纳米粒的药动学研究。
Objective. To establish a RP-HPLC method for determination of plasma progesterone and to apply the method for pharmacokinetics study of progesterone-loaded lipid nanoparticles after oral administration in rats. Methods: The plasma samples were collected from castrated rat after oral administration of progesterone-loaded lipid nanoparticles and extracted by acetic ether. The determination was performed on a Hypersil C18 column (150 mm × 3.9 mm, 5 μm) with a mobile phase consisting of methanol and water (60:40) at a flow-rate of 0.6 ml/min. The UV detector was at 240 nm and danazol was used as internal standard. Results: Good linearity was obtained over the range of 0.02-2 μg/ml progesterone in plasma(r=0. 9999,n=3). The quantification limit was (0. 02±0. 004) μg/ml(n=3) and the limit of detection was 0. 005 μg · mL^-1 (S/N≥3). The inter- and intra-day RSDs were all less than 10~ for quality control samples at high-, medium- and low-concentrations. The average absolute recovery rate was 90.5% and the average method recovery was in the range of 93. 4%-107. 5%. The plasma concentration-time curves indicated that tmax was delayed after administration of progesteroneloaded lipid nanoparticles, and the bioavailability was increased significantly, compared with contrast solution. Conclusion. The method developed is stable, simple, rapid, accurate, sensitive and applicable for determining plasma concentrations of progesterone of progesterone-loaded lipid nanoparticles in pharmacokinetic studies.
出处
《浙江大学学报(医学版)》
CAS
CSCD
2008年第2期146-149,155,共5页
Journal of Zhejiang University(Medical Sciences)
基金
浙江省教育厅科研基金资助项目(20061326)