反相高效液相色谱法测定兰索拉唑及其代谢产物 5’- 羟基兰索拉唑和兰索拉唑砜的血药浓度(英文)

Determinationoflansoprazoleanditsmetabolites5'-hydroxylansoprazole and lansoprazole sulphone in human plasma by reversed-phase HPLC

目的 :建立测定兰索拉唑及其代谢产物 5’ 羟基兰索拉唑和兰索拉唑砜的血药浓度的方法 ,用于测定其血药浓度并进行临床药代动力学研究。方法 :采用高效液相 二极管阵列色谱法测定兰索拉唑及其代谢产物 5’ 羟基兰索拉唑和兰索拉唑砜的血药浓度。结果 :兰索拉唑的校正标准曲线为Y =0 .0 135 8+0 .0 0 12 2 7X (r =0 .9994 ) ,其 2 5 ,2 0 0 ,2 0 0 0μg·L-1三浓度的血样回收率分别为 87.99% ,94 .38% ,77.2 1% ;精密度分别 7.79% ,1.2 1% ,5 .4 9% ;5’ 羟基兰索拉唑的校正标准曲线分别为Y=0 .0 0 2 5 36+0 .0 0 0 912 6X (r=0 .9990 ) ,其 2 0 ,10 0 ,5 0 0 μg·L-1三浓度的血样回收率分别为 85 .85 % ,87.64% ,10 7.70 % ;精密度分别为 10 .73% ,6.98% ,5 .62 % ;兰索拉唑砜的校正标准曲线分别为Y =0 .0 1486+0 .0 0 1462X (r =0 .9995 ) ,其 2 0 ,10 0 ,10 0 0μg·L-1三浓度的血样回收率分别为 79.84 % ,85 .18% ,10 0 .68% ;精密度分别为 9.2 2 % ,2 .36% ,4 .81%。志愿受试者禁食口服 30mg兰索拉唑胶囊后 ,兰索拉唑及其代谢产物 5’ 羟基兰索拉唑和兰索拉唑砜的Cmax 分别为 113.2 1,15 61.5 4 ,131.14μg·L-1。结论 :此方法可满足测定要求 ,可用于兰索拉唑的药代动力学研究。

AIM: To set up a method to determine the blood concentration of lansoprazole and its metabolites 5'-lansoprazole and lansoprazole sulphone. METHODS: The blood concentration of lansoprazole was determined by HPLC. RESULTS: Calibrated standard curve of lansoprazole in blood was Y= 0.0136+ 0.0012X (r= 0.9994); the recoveries at three concentrations of 25, 200, and 2000 μg·L -1 were 87.99%, 94.38%, and 77.21%, respectively; and the RSD values were 7.79%, 1.21%, and 5.49%, respectively. Calibrated standard curve of its metabolite 5'-OH lansoprazole in plasma was Y= 0.0025+ 0.000926X (r= 0.9990). The recoveries at three concentrations (20, 100, and 500 μg·L -1) were 85.85%, 87.64%, and 107.70%, respectively; and the RSD values were 10.73%, 6.98%, and 5.62%, respectively. Calibrated standard curve of another metabolite lansoprazole sulphone in plasma was Y= 0.01486+ 0.001462X (r= 0.9995), the recoveries at three concentrations (20, 100, and 1000 μg·L -1) were 79.84%, 85.18%, and 100.68%; respectively; and the RSD values were 9.22%, 2.36%, and 4.81%, respectively. After 30 mg of lansoprazole was administered by a volunteer po, the values of C max of 5'-OH lansoprazole, lansoprazole, and lansoprazole sulphone were 113.21, 1561.54, and 131.14 mg·L -1, respectively. CONCLUSION: The method is accurate for determining the blood concentration of lansoprazole and its metabolites 5'-lansoprazole and lansoprazole sulphone.