摘要
目的:建立测定大鼠血浆中帕潘立酮浓度的方法并研究其药动学。方法:6只大鼠单剂量灌胃给予帕潘立酮2.5mg。以利培酮为内标,采用反相-高效液相色谱法测定给药前及给药后0.25、0.5、1、1.5、2、4、8、12、24、36、48h的血药浓度。采用DAS软件计算药动学参数。色谱柱为Scienhome KromasilC18,流动相为乙腈-0.1mol/L Na2HPO4(pH6.0)(62∶38),流速为1.0ml/min,检测波长为237nm,柱温为35℃,进样量为20μl。结果:帕潘立酮检测质量浓度的线性范围为0.01～0.40μg/m(lr=0.9995),方法回收率为98.7%～102.2%,萃取回收率为82.8%～85.8%,日内和日间RSD均<9%。帕潘立酮在大鼠体内吸收符合二室模型,主要药动学参数cmax为(102.3±21.56)μg/L、tmax为(1.5±0.22)h、t1/2β为(14.969±5.651)h、Vd为(17.568±9.688)L、AUC0-48h为(1799.721±329.573)μg·h/L。结论:本方法适用于帕潘立酮的血药浓度测定;帕潘立酮在大鼠体内消除较慢,分布较广。
OBJECTIVE： To establish the method for the determination of paliperidone （PA） concentration in the rat plasma, and to study pharmacokinetics of PA in rats. METHODS： 6 rats were given a single dose of 2.5 mg PA. The plasma concentration of PA was determined by RP-HPLC before medication and 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48 h after medication, using risperidone as internal standard. Pharmaceutical parameters were calculated with DAS software. The analytic column was Scienhome Kromasil C18, with acetonitrile-0.1 mol/L Na2HPO4 （pH 6.0） （62 ： 38） at the flow rate of 1.0 ml/min. The detection wavelength was set at 237 nm and column temperature was 35 ℃. The injection volume was 20 μl. RESULTS： The linear range of PA were 0.01- 0.40 μg/ml （r=0.999 5）. The method recoveries were 98.7%-102.2%, and extraction recoveries were 82.8%-85.8%. RSD of inter-day and intra-day were less than 9 %. The plasma concentration-time curve of PA was fitted to two-compartment open pharmacokinetic model. The main pharmacokinetic parameters were as follows：cmax was （102.3 ± 21.56） μg/L; tmax was （1.5 ± 0.22） h; t1/2β was （14.969 ± 5.651） h; Vd was（17.568 ± 9.688） L; AUC0-48h was （1 799.721 ± 329.573） μg.h/L. CONCLUSIONS： This method is suitable for the determination of PA concentration in rat plasma. PA is eliminated slowly and then distributed widely in rats in vivo.
出处
《中国药房》
CAS
CSCD
2013年第17期1569-1571,共3页
China Pharmacy
