摘要
目的:建立间尼索地平的高效液相色谱分析方法,研究其在Beagle犬体内的药代动力学。方法:血浆样品经液-液萃取后,用HPLC法进行分析。色谱柱为Diamond C18柱(250 mm×4.6 mm,5μm);流动相为乙腈-20 mmol/L KH2PO4(60∶40);流速为1 mL/min;紫外检测波长为237 nm。结果:Beagle犬口服3种不同浓度的间尼索地平(1.0,2.5,12.5 mg/kg)后,血药浓度经时曲线均呈现明显的双峰现象。第1次达峰时间在1 h左右,第2次达峰时间在2-3 h,血药浓度峰值cmax较低。cmax与AUC均与剂量呈正相关。结论:间尼索地平经口服给药后,吸收较迅速,cmax较低可能与肝脏的首过效应有关;双峰现象可能与药物存在肝肠循环有关。
Aim：To develop a sensitive and rapid HPLC method for the determination of m-nisoldipine （M-Nis）in Beagle dog＇s plasma and to study its pharmacokinetics. Methods：After oral dosing of M-Nis to dogs, plasma samples, into which nimodipine （Nimo） was added as internal standard, were extracted with diethyl ether. Following the drying, the residues were reconstituted and injected into HPLC which was operated on Diamond C18 analytical column （250 mm× 4.6 mm, 5 μm）with the mobile phase consisting of acetonitrile-20 rnraol/L-KH2PO4（60：40） at a flow rate of 1.0 mL/min. The elution was monitored at the wavelength of 237 m. Results： Double peaks appeared in the plasma concentration-time curves in Beagle dogs receiving oral doses of 1.0, 2.5 and 12.5 mg/kg. The time reaching to the first peak was around 1 h, and the time reaching to the second peak was 2 - 3 h. Cmax Was found to be low. Furthermore, both Cmax and AUC increased in proportional to the dosages. Conclusion： M-Nis was quickly absorbed after oral administration. The low Cmax Was possibly related to the first-pass effect, while the double peaks might be relevant to enteroheptic cycling.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2007年第2期140-143,共4页
Journal of China Pharmaceutical University
基金
河北省卫生厅重大攻关课题资助项目(No.04002)~~
