苯酰甲硝唑分散片的血药浓度及生物等效性测定

Determination of Serum Concentration and Bioequivalence for Benzoyimetronidazole Dispersible Tablets

目的:建立人血清中苯酰甲硝唑体内代谢产物--甲硝唑的反相高效液相色谱分析方法,比较苯酰甲硝唑分散片和苯酰甲硝唑胶囊生物等效性。方法:采用Eurosphex-100 C18柱,以乙腈-KH2PO4(0．01 mol·L-1)(22:78,v／v)为流动相,替硝唑作内标,紫外检测波长为318 nm,测定血清中甲硝唑的血药浓度。结果:血清中甲硝唑的浓度在0．1-20．0μg·ml-1范围内线性关系良好,r=0．999 9(n=8)。受试制剂及参比制剂的Cmax分别为(10．475±2．135)和(10．118±2．116),Tmax分别为(4．000±1．414)和(4．667±1．138)h,t1／2分别为(11．247±2．264)和(10．800±2．000)h,根据AUC0→t计算受试制剂的相对生物利用度为(100．9±20．2)％。结论:本方法操作简便、灵敏度高、重现性好,可用于血清中甲硝唑浓度的测定。苯酰甲硝唑分散片和苯酰甲硝唑胶囊具有生物等效性。

Objective： To develop a RP-HPLC method for the blood concentration of metrortidazole which was the metabolite of benzometronidazole and compare the bioequivalence between dispersible tablets and capsules of benzoylmetronidazole. Method： Euros- phex-100 Cl8 column was used,the mobile phase was constituted by acetonitrile -0.01 mol·L^-1 potassium dihydrogen phosphate buffer （22：78 ,v/v）. The detection wavelength was 318 nm. Result： The standard curve was linear within a concentration range of 0. 1 - 20.0 μg·L^-1 with r= 0. 999 9 （ n = 8 ）. The main pharmaeokinetic parameters Cmax,Tmax, t1/2 were （ 10. 475 ± 2. 135 ） μg· ml^-1, （4. 000 ± 1. 414） h and （ 11. 247 ± 2. 264 ） h for the reference tablets, also （ 10.118 ± 2.116 ） μg· ml^-1, （ 4.667 ± 1. 138 ） h and （ 10.800 ± 2. 000） h for the test tablets respectively, the relative bioavalability of the test tablets was （ 100.9 ± 20.2） %. Conclusion： This method is simple, sensitive, accurate and fine reproducible for determination of serum concentration in metronidazole. The results of statistical analysis demonstrated that the two preparations of benzoylmetronidazole are bioequivalent.