五味子乙素对阿霉素在大鼠体内的药代动力学影响

Effects of schisandrin B on pharmacokinetics of doxorubicin in rats

考察五味子乙素和阿霉素联合用药后对SD大鼠体内阿霉素药代动力学行为的影响。建立了LC-MS/MS法测定SD大鼠血浆中阿霉素及其主要代谢产物阿霉素醇,采用Agilent Eclipse XDB-C18色谱柱(100 mm×2. 1 mm,3. 5μm),流动相为0. 1%甲酸水溶液和乙腈,梯度洗脱方式,电喷雾离子化正离子扫描模式下,离子对分别为m/z 544. 2→397. 3(阿霉素)、m/z 546. 2→399. 2(阿霉素醇)、m/z 528. 2→381. 2(柔红霉素,内标)。阿霉素在0. 500~500 ng/m L,阿霉素醇在0. 200~50. 0ng/m L范围内线性关系良好,精密度和准确度均符合要求,各浓度提取回收率和基质效应的变异系数均小于15%。阿霉素在单独给药和联合给药组的AUC0-t分别为(605. 69±145. 84)和(564. 53±23. 99) ng·h/m L,阿霉素醇的AUC0-t分别为(26. 69±13. 41)和(29. 00±2. 78) ng·h/m L。结果表明五味子乙素不影响阿霉素在SD大鼠体内的药代动力学行为。

To investigate the effect of combination of schisandrin B and doxorubicin on the pharmacokinetic behavior of doxorubicin in SD rats.An LC-MS/MS method was established for the determination of doxorubicin and its main metabolite doxorubicinol in SD rats plasma.Separation was performed on Agilent Eclipse XDB-C 18 column(100 mm×2.1 mm,3.5μm)using 0.1%formic acid solution and acetonitrile as mobile phase with a liner gradient program.The ion transitions were performed under ESI position model at m/z 544.2→397.3(doxorubicin),m/z 546.2→399.2(doxorubicinol),m/z 528.2→381.2(daunorubicin,internal standard).Calibration curves of doxorubicin(0.500-500 ng/mL)and doxorubicinol(0.200-50.0 ng/mL)showed good linear regression.The precision and accuracy met the requirements.The variation coefficient of extraction recovery and matrix effect was less than 15%.The AUC 0-t of doxorubicin were(605.69±145.84)and(564.53±23.99)ng·h/mL in alone and combined group,respectively.The AUC 0-t of doxorubicinol were(26.69±13.41)and(29.00±2.78)ng·h/mL,respectively.Results indicated that,schisandrin B had not affected the pharmacokinetic behavior of doxorubicin in SD rats.