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目的运用HPLC法建立大鼠血浆中米托蒽醌浓度的检测方法。方法用10%三氯乙酸甲醇沉淀蛋白的方法处理血浆样本,色谱柱为XBridge-C_(18)色谱柱(150 mm×2.1 mm,3.5μm),流动相为0.3%庚烷磺酸钠溶液(用磷酸调p H=2.0)-乙腈(72∶28),流速1.0 m L·min~(-1),检测波长λ240 nm,内标为安非他酮。并用所建立的方法研究米托蒽醌在大鼠体内的药动学。结果血浆中米托蒽醌在质量浓度100~10 000μg·L~(-1)内线性关系良好(r=0.999 6),日内和日间精密度良好(RSD均<6%),平均回收率>80%,短期室温和长期冷冻保存条件下稳定性良好(RSD均<8%)。静脉注射给予米托蒽醌5 mg·kg~(-1),大鼠的AUC_(0→t)为(1 178.44±70.07)μg·h·L~(-1),t_(1/2z)为(0.39±0.12)h,CLz/F为(3.91±0.26)L~(-1)·h·kg~(-1),Vz为(2.18±0.63)L·kg~(-1),t_(max)为(0.22±0.04)h,ρ_(max)为(2 380.91±360.12)μg·L~(-1)。结论该方法操作简便,特异性强且稳定可靠,适用于米托蒽醌的药动学研究。
Objective To establish a method for the determination of mitoxantrone in rat plasma by HPLC. Methods Plasma samples were precipitated with 10% trichloroacetic acid in methanol. The column was XBridge-C 18 column (150 mm × 2.1 mm, 3.5 μm) with a mobile phase of 0.3% sodium heptanesulfonate solution The pH value was adjusted to 240 nm with p H = 2.0) -acetonitrile (72:28) at a flow rate of 1.0 mL · min -1. The internal standard was bupropion. The pharmacokinetics of mitoxantrone in rats was studied with the established method. Results The plasma mitoxantrone had good linearity (r = 0.999 6) and good precision (RSD <6%) in the range of 100-10 000 μg · L -1, the average recovery > 80%, good stability under short-term room temperature and long-term cryopreservation (RSD <8%). The AUC_ (0 → t) of the rats was (1 178.44 ± 70.07) μg · h · L -1, t 1/2 (1 / 2z) (0.39 ± 0.12) h, CLz / F was (3.91 ± 0.26) L · h · kg -1, Vz was 2.18 ± 0.63 L · kg -1, t_ (max) was (0.22 ± 0.04) h and ρ max was (2 380.91 ± 360.12) μg · L -1. Conclusion The method is simple, specific, stable and reliable and is suitable for pharmacokinetic studies of mitoxantrone.