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
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摘要: 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，3.5 μm)，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/mL，阿霉素醇在0.200~50.0 ng/mL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/mL，阿霉素醇的AUC0-t分别为(26.69±13.41)和(29.00±2.78)ng·h/mL。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。Abstract: 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-C18 column(100 mm×2. 1 mm, 3. 5 μm)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 AUC0-t of doxorubicin were(605. 69±145. 84)and(564. 53±23. 99)ng ·h/mL in alone and combined group, respectively. The AUC0-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.
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Keywords:
- schisandrin B /
- doxorubicin /
- combination /
- drug-drug interaction /
- pharmacokinetics
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