HPLC测定犬血浆中盐酸伪麻黄碱浓度及西嗪伪麻缓释片的初步体内药动学研究

 目的建立血浆中盐酸伪麻黄碱(PSE)的HPLC测定法,并用于在犬体内的初步药动学的研究。方法以盐酸苯丙醇胺(Phen)为内标,血浆样品经简单的乙醚萃取后用HPLC直接进样检测。结果以甲醇-水(11:29)为流动相,采用Lichrospher C₁₈能使PSE,Phen及血浆中的杂质达到基线分离;实测了犬口服西嗪伪麻缓释片剂(受试制剂,T片)和PSE普通片剂(参比制剂,C片)后不同时间点下血浆中PSE的浓度,并获得主要药动学参数分别为:t_1/2(T)(4.66±1.43)h,t_1/2(C)(3.78±1.91)h,t_max(T)(4.0±1.4)h,t_max(C)(2.3±0.5)h,c_max(T)(5.47±2.41)μmol·L^-1,c_max(C)(12.31±3.57)μmol·L^-1。结论血浆中的西替利嗪及杂质不干扰样品的测定,PSE的浓度在0.1～10.0μmol·L^-1内线性良好,符合生物样品分析要求;犬单剂量口服T片剂后,PSE达峰时间明显滞后,t_1/2延长,达峰浓度明显降低,MRT明显增大,达到缓释的目的。

HPLC determination of pseudoephedrine hydrochloride in dog plasma and the preliminary pharmacokinetic study of compound pseudoephedrine cetirizine sustained release tablets

OBJECTIVE To develop a specific and rapid HPLC method to determine Pseudoephedrine hydrochloride (PSE) in plasma and to investigate the pharmacokinetics of compound pseudoephedrine cetirizine sustained release tablets in dogs. METHODS The plasma samples were extracted by ether. Phenylalanine hydrochloride(Phen) was used as the internal standard. Lichrospher C₁₈ column was used with a mobile phase of methanol-water(11:29) .RESULTS PSE, Phen and the impurities in plasma were separated efficiently. A good linearity over the range of 0.10 to 10.00 μmol·L^-1 was achieved. The recovery, accuracy and precision of intra-day and inter-day were all qualified.The concentrations of PSE in dog plasma were measured at different time points after oral administration of compound pseudoephedrine cetirizine sustained release tablets (T) and regular tablets? .The main pharmacokinetic parameters were obtained as follows: t_1/2(T) (4.66±1.43)h,t_1/2? (3.78 ± 1.91)h,t_max(T)(4.0± 1.4)h,t_max?(2.3 ± 0.5)h,c_max(T) (5.47 ±2.41)μmol·L^-1, c_max?( 12.31 ±3.57)μmol·^-1.CONCLUSION The sustained release PSE tablet released more slowly.Its t_1/2 was extended, and its maximal concentration was decreased significantly.