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目的:建立小鼠血浆中1,3-二苯-1,3-丙二酮(1,3-diphenyl-1,3-propanedione,DPPD)的高效液相色谱测定法,应用该方法测定DPPD在小鼠体内的药代动力学参数,并为DPPD的临床应用提供依据。方法:采用正交试验设计法优化小鼠血浆样本的前处理方法,Symmetry C18色谱柱分离,保留时间定性,内标法定量。雄性ICR小鼠灌胃给予DPPD,不同时间点内眦取血,测定DPPD的经时血药浓度。Thermo Kinetica4.4.1软件计算相应的药代动力学参数。结果:小鼠血浆中DPPD浓度在0.05μg/ml～20μg/ml范围内线性关系良好(r>0.99);加标回收率为91.7%～102.7%。血浆样品在-80℃冰箱中至少可保存15 d。主要药代动力学参数为:t1/2=3.24±0.78 h,Tmax=2.50±0.42 h,Cmax=1.30±0.84μg/ml,AUC0～∞=6.63±2.80 h.μg/ml。结论:该方法准确、灵敏,适用于DPPD小鼠体内药代动力学研究。
OBJECTIVE: To establish a method for the determination of 1,3-diphenyl-1,3-propanedione (DPPD) in mouse plasma by high performance liquid chromatography (HPLC) Mouse pharmacokinetic parameters in vivo, and provide the basis for the clinical application of DPPD. Methods: The orthogonal design was used to optimize the pretreatment method of mouse plasma samples. Symmetry C18 column was used for separation and retention time was qualitatively determined by internal standard method. Male ICR mice given intragastric administration of DPPD, blood collected at different time points, measured DPPD time-dependent plasma concentrations. Thermo Kinetica 4.4.1 software calculates the corresponding pharmacokinetic parameters. Results: The plasma concentration of DPPD in the range of 0.05μg / ml ~ 20μg / ml had a good linear relationship (r> 0.99). The recoveries of the standard addition ranged from 91.7% to 102.7%. Plasma samples can be stored in a refrigerator at -80 ° C for at least 15 days. The main pharmacokinetic parameters were: t1 / 2 = 3.24 ± 0.78 h, Tmax = 2.50 ± 0.42 h, Cmax = 1.30 ± 0.84 μg / ml and AUC0 ~ ∞ = 6.63 ± 2.80 h.μg / ml. Conclusion: This method is accurate and sensitive and suitable for pharmacokinetic studies in DPPD mice.