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目的建立生物样品中苯烯莫德的高效液相色谱法(HPLC)测定方法并进行大鼠体内药物动力学、组织分布及乳猪皮肤分布的研究。方法大鼠皮下注射苯烯莫德后,于不同时间点眼眶静脉丛采血,乙酸乙酯提取大鼠血浆及组织中的苯烯莫德。乳猪涂抹苯烯莫德后,不同时间点于前腔静脉取血,取皮肤。HPLC测定生物样品中苯烯莫德的含量,DAS软件计算药物动力学参数。结果大鼠皮下注射3种剂量(3、9和27 mg/kg)苯烯莫德,体内血药浓度-时间曲线下面积(AUC)符合二室模型的动力学特征,按二室模型计算的t_(1/2α)分别为(0.65±0.27)、(0.78±0.13)和(0.53±0.26)h,t_(1/2β)分别为(3.40±0.88)、(3.80±0.62和(4.70±0.41)h,达峰浓度分别为(84.89±13.76)、(166.90±31.37)和(385.20±98.68)ng/ml,AUC0-t分别为(243.20±34.01)、(786.10±176.90)、(2 677.00±255.10)ng/ml·h。SD大鼠皮下注射苯烯莫德(9 mg/kg)后10 min,各脏器中即有分布,其中肝、肾、脾、胃、甲状腺、卵巢、胰腺、皮肤中含量较高。乳猪皮肤涂抹给药24 h后,皮肤中苯烯莫德药物含量达(104.17±13.36)μg/g,乳猪血药浓度低于最低定量浓度(5 ng/ml)。结论本方法快速、准确、简便,能够满足苯烯莫德药物动力学研究要求。苯烯莫德大鼠皮下注射给药后其进入体内血液循环的药量较少。乳猪皮肤涂抹给药后皮肤内药物含量较高,血浆浓度极低。
OBJECTIVE To establish a high performance liquid chromatography (HPLC) method for the determination of benemox in biological samples and to study the pharmacokinetics, tissue distribution and distribution of suckling pig skin in rats. Methods The rats were injected subcutaneously with entermole, and the orbital venous plexus was collected at different time points. The enolase in rat plasma and tissues was extracted with ethyl acetate. Piglets smear Benzene Maud, different time points in the anterior vena cava blood, take the skin. HPLC was used to determine the concentration of benemox in biological samples and the DAS software was used to calculate the pharmacokinetic parameters. Results Three doses (3, 9 and 27 mg / kg) of enkemozole were injected subcutaneously in rats, and the area under the curve of plasma concentration-time curve (AUC) was in accordance with the kinetic characteristics of two- t 1/2 1/2 were (0.65 ± 0.27), (0.78 ± 0.13) and (0.53 ± 0.26) h respectively, t 1/2 (3.40 ± 0.88), (3.80 ± 0.62 and 4.70 ± 0.41 ) h and the peak concentrations were (84.89 ± 13.76), (166.90 ± 31.37) and (385.20 ± 98.68) ng / ml respectively.The AUC0-t were 243.20 ± 34.01, 786.10 ± 176.90 and 2677.00 ± 255.10) ng / ml · h.SD rats were subcutaneously injected with bensene (9 mg / kg) 10 min after the subcutaneous injection of various organs, including liver, kidney, spleen, stomach, thyroid, ovary, pancreas, The content of testosterone in skin was (104.17 ± 13.36) μg / g after 24 h, while the blood concentration of suckling pigs was lower than the lowest concentration (5 ng / ml) .Conclusion The method is rapid, accurate and simple and can meet the demand of the study of the pharmacokinetics of benepromide.Moreover, the dose of bennemodul administered subcutaneously into the blood circulation is less. After the skin of high drug content, plasma concentration Very low.