摘要
目的：建立测定替米沙坦血浆浓度的高效液相．荧光检测法（HPLC），考察替米沙坦的药代动力学及生物等效性．方法：24例健康受试者单剂量交叉口服40mg替米沙坦片供试制剂或参比制剂后，用HPLC测定替米沙坦血药浓度并计算药动学及相对生物利用度，进而对主要药动学参数进行统计分析．色谱柱为Diamonsil C18柱（5μm，4．6mm×150mm），以乙腈．磷酸二氢钾缓冲液（61：39，磷酸调pH=3．74）为流动相，流速1．0mL／min，坎地沙坦为内标，荧光检测波长入Ex：305nm，入Em=365nm．结果：测定替米沙坦的线性范围为0．5～144ng／mL，r=0．9998，绝对回收率在79．62％～85．69％（n=5），相对回收率在101．92％～108．95％（n=5），13内和13间RSD分别为4．23％～9．80％和4．03％～9．95％（n=5）．供试制剂与参比制剂的AUC0-96分别为888．90±406．49和895．03±364．53．结论：两种替米沙坦制剂均具有生物等效性．
AIM： To develop a HPLC method with fluorescent detection to determine telmisartan in human plasma and study the pharmacokinetics profiles and bioequivalence of telmisartan in healthy Chinese volunteers. METHODS： In a randomized two period crossover study, 24 healthy male volunteers received single dose of 40 mg telmisartan. The serum concentration of telmisartan was determined by HPLC method. The pharmacokinetic parameters of the two preparations （test and reference） and the relative bioavailability after oral administration were calculated with statistic analysis. The column was Diamonsil C18 （5μm, 4.6 mm × 150 mm）. The mobile phase consisted of acetonitrile-potassium dihydrogen phosphate buffer solution （61：39, pH adjusted to 3.74 with H3PO4 ） at a flow rate of 1.0 mL/min. The internal standard was candesartan. The fluorescence detector was operated at λEx =305 nm and λEm = 365 nm. RESULTS： The calibration curve of telmisartan was linear in the range of 0.5 - 144 ng/mL （ r = 0.9998 ）. The absolute recovery was 79.62% - 85.69% （ n = 5） , and the relative recovery was 101.92% - 108.95% （ n = 5） , and the intra-day and inter-day RSDs were 4.23% -9.80% and 4.03% - 9.95% （ n = 5 ）. AUC0-96 of the test and reference preparations was 888.90± 406.49 and 895.03±364.53, respectively. CONCLUSION： Statistical analysis showed that the two preparations were bioequivalent.
出处
《第四军医大学学报》
北大核心
2006年第18期1723-1725,共3页
Journal of the Fourth Military Medical University
关键词
替米沙坦
色谱法
高压液相
生物等效性
telmisartan
chromatography, high pressure liquid
bioequivalent
