UPLC-MS法研究艾迪注射液对大鼠体内阿霉素药代动力学的影响

Effect of Aidi injection on in vivo pharmacokinetics of doxorubicin in Sprague-Dawley rats by UPLC-MS method

目的研究艾迪注射液(Aidi injection,ADI)对阿霉素(doxorubicin,DOX)及其活性代谢产物阿霉素醇(doxorubicinol,DOXol)药代动力学的影响,探讨ADI与DOX联合用药的临床意义。方法采用对比实验,将SD大鼠随机分为DOX单独给药组和DOX与ADI联合给药组,联合给药组提前连续腹腔注射ADI 14 d,再尾静脉注射DOX 7 mg·kg^(-1),采用超高效液相色谱-质谱联用法(UPLC-MS)在选择离子监测(SIR)模式下,测定DOX单独给药和与ADI联合给药后不同时间大鼠血浆中DOX和DOXol浓度,比较单独和联合给药后DOX和DOXol的体内药代动力学过程差异。结果大鼠血浆中DOX和DOXol在测定范围内均呈良好线性关系(r>0.99),日内和日间精密度RSD均小于10%,准确度大于85%,血浆中提取回收率均大于80%,提取方法稳定可靠;单独给药和与ADI联合给药的药代动力学参数无明显差异。结论 ADI对DOX的体内药代动力学过程无明显影响。

Aim To investigate the effect of Aidi injection（ ADI） on the pharmacokinetics of doxorubicin（ DOX） and doxorubicinol（ DOXol） in rats. In addition,to explore the clinical significance of ADI and DOX combination. Methods SD rats were divided into single and combined administration groups. The combined group was injected with DOX（ 7 mg·kg^（-1））after intraperitoneally treated with ADI（ 10 m L ·kg^（-1）,once a day for continuous 14 d）,while the single group was injected with DOX and saline. The concentration of DOX in plasma was determined by UPLCMS method,and then the difference in pharmacokinetic parameters were compared. Results The determination methods with good precision and stability were suitable for the assay of DOX and DOXol in biological samples. The pharmacokinetic parameters of DOX and DOXol had no significant difference in two groups.Conclusion There is no obvious effect of ADI on the pharmacokinetics of DOX.