关键词: 头孢妥仑, 高效液相色谱法, 肝灌流, 多药耐药相关蛋白2

Abstract: AIM: To develop a high-performance liquid chromatography internal standard method for determining of cefditoren in the rat plasma, bile and urine, and to clarify the relation between multidrug resistance- associated protein 2 (Mrp2) and biliary excretion of cefditoren using perfused rat livers. METHODS: 4-dimethylaminoantipyrine was used as the internal standard.Chromatographic separation was performed on a C₁₈ UG 120 column (4.6 mm ×250 mm, 5 μm) and mobile phase was composed of 0.1 % ammonium acetate and methyl alcohol (67:33, V/V). The flow rate was 0.8 mL/min and 25 μL of mixture was injected.Perfused rat livers were performed to investigate whether cefditoren was transported via Mrp2. We established the control (cefditoren 1 μmol/L) and experimental group (cefditoren 1 μmol/L added the inhibitor of Mrp2-probenecid, 20 μmol/L).Perfusate samples and bile were collected at setting times.Cefditoren was determined by HPLC.We compared the hepatic extraction ratio and cumulative biliary excretion rates in control and experimental groups. RESULTS: The concentration range of cefditoren was 0.1 -4 μg/mL in plasma, 0.1 -5 μg/mL in bile and in urine, with good linearity.The relative recovery was 85 %- 110 %.The intra- and inter-day RSD were <13.5 %. The hepatic extraction ratio showed no statistically significant differences, whereas cumulative biliary excretion rates were significantly reduced to 40.0 % compared to control over 25 min in experimental group. CONCLUSION: It can be used for the determination of cefditoren concentration in plasma, bilary and urinary samples and for pharmacokinetic study since it is economic, simple, sensitive and fast method.Cefditoren is the substrate of Mrp2, which is related with biliary excretion of cefditoren.

Key words: cefditoren, HPLC, perfused livers, multidrug resistance-associated protein 2