奥硝唑血药浓度的高效液相色谱法测定及其国产和进口片剂的药动学和生物等效性研究(英文)  

Determination of ornidazole in plasma by HPLC and study on its pharmacokinetics and bioequivalence of domestic and imported tablets in 18 healthy volunteers

作　　者：李芹[1] 陈建中[2] 郭瑞臣[3] 

机构地区：[1]中国海洋大学海洋药物与食品研究所,山东青岛266003 [2]山东省聊城市人民医院药学部,山东聊城252000 [3]山东大学齐鲁医院临床药理研究所,山东济南250012

出　　处：《中国现代应用药学》2004年第2期129-132,共4页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的　建立血浆中奥硝唑浓度的反相高效液相色谱分析方法 ,并用此法研究了国产和进口奥硝唑片剂在健康人体内的药动学及生物等效性。方法　用甲醇 /异丙醇 (5 0 / 5 0 )提取样本 ,采用KromasilC18色谱柱 ,以甲醇 :0 .4 %HAc(5 0∶5 0 )为流动相 ,流速 0 .8mL·min-1,紫外检测波长 316nm。 18名健康男性志愿者随机交叉口服国产及进口奥硝唑片 1.5g,测定其药动学参数 ,评价两种制剂的生物等效性。结果　奥硝唑在 2 .0～ 2 0 .0 μg·mL-1范围内呈线性 ,r=0 .9997,最低检测限 0 .2 μg·mL-1。低、中、高浓度 (2 .0 ,10 .0 ,2 0 .0 μg·mL-1)的方法回收率分别为 10 0 .36 % ,98.2 1%和 97.4 2 % ,日间及日内RSD分别 <6 %和 <7%。药动学研究表明 ,口服奥硝唑国产与进口制剂的药 时曲线符合有滞后时间的二室模型。其主要药动学参数如下 :t1/ 2 (β) 分别为 (16 .2 9± 2 .2 0 )h和 (15 .85± 2 .2 6 )h ;Tmax分别为 (1.6 7± 0 .4 9)h和 (1.75± 0 .4 8)h ;Cmax分别为 (2 2 .0 3± 3.5 3)mg·L-1和 (2 2 .5 8± 5 .94 )mg·L-1;AUC0～ 72 分别为 (4 4 4 .5 6± 5 5 .87)mg·h·L-1和 (4 33.31± 5 8.5 2 )mg·h·L-1;AUC0～∞ 分别为 (4 6 2 .95± 5 5 .35 )mg·h·L-1和 (4 5 1.6 7± 5 7.97)mg·h·L-1。?OBJECTIVE To establish a reversed HPLC method for the determination of ornidazole in human plasma, and study the pharmacokinetics and bioequivalence of domestic and imported tablets in healthy volunteers.METHOD The drug was extracted from plasma with methanol and isopropanol (50∶50), and then analyzed by HPLC with a C 18 5μm 250×4.6mm column and UV detector set at 316nm. The mixture of methanol and 0.4% glacial acetic acid (50∶50) was used as the mobile phase. The flow rate is 0.8mL·min -1 . 1.5g single oral dose of domestic and imported ornidazole tablets were given to 18 healthy volunteers in an open randomized crossover study. The pharmacokinetic parameters as well as relative bioavailability were measured.RESULTS The calibration curve was linear within the range of 2.0～20.0μg·mL -1 and the measurable lowest limit was 0.2μg·mL -1 . The average recovery of ornidazole at the concentrations of 2.0, 10.0, 20.0μg·mL -1 was 100.36%, 98.21% and 97.42%, respectively. The RSD of the within-day and between-day were less than 7% and 6%, respectively. The results showed that the concentration-time curves of the two preparations were fitted to a two -compartment model with a lag time. The major pharmacokinetic parameters of domestic and imported ornidazole tablets were shown respectively as following: t 1/2(β) were (16.29±2.20)h and (15.85±2.26)h ;T max were (1.67±0.49)h and (1.75±0.48)h; C max were (22.03±3.53)mg·L -1 and (22.58±5.94)mg·L -1 ;AUC 0～72 were (444.56±55.87)mg·h·L -1 and (433.31±58.52)mg·h·L -1 ; AUC 0～∞ were (462.95±55.35)mg·h·L -1 and (451.67±57.97)mg·h·L -1 . There were no significant difference between the main pharmacokinetic parameters of the two preparations (P>0.05). The relative bioavailability of domestic tablet was (102.91±8.93)%.CONCLUSIONS This HPLC method is simple, sensitive and accurate. It is suitable for routine determination of ordinazole levels in human plasma and for i

关 键 词：奥硝唑 高效液相色谱法 药动学 生物等效性 

分 类 号：R917.01[医药卫生—药物分析学] R978[医药卫生—药学]