Peng Y M, Ormberg D, Alberts D S, Davis T P
J Chromatogr. 1982 Dec 10;233:235-47. doi: 10.1016/s0378-4347(00)81750-8.
Bisantrene and mitoxantrone are two new anthracene derivatives which have shown significant antitumor activity against a wide variety of animal tumors and in human phase I and II clinical trials. We have developed a rapid, simple and sensitive sample cleanup procedure and high-performance liquid chromatographic (HPLC) assay for both drugs. This method uses a commercially available mini-cartridge with C18 reversed-phase packing to isolate the drugs from the biological matrix prior to HPLC. For both drugs the average recovery of the assay was 98 +/- 6% with a coefficient of variation (C.V.) of less than 7%. Using this new method our assay sensitivity has improved to less than 10 ng/ml for bisantrene and 1 ng/ml for mitoxantrone, allowing us to document a prolonged terminal phase plasma half-life for both bisantrene and mitoxantrone. Equilibrium dialysis studies showed that both drugs are highly protein bound. Mitoxantrone appears less stable in human plasma than bisantrene. Recoveries from plasma after a 24-h incubation at 25 and 37 degrees C were 40 and 20% for mitoxantrone and 90 and 85% for bisantrene, respectively. Addition of ascorbic acid prior to incubation of mitoxantrone in human plasma at 37 degrees C resulted in less than a 10% decrease in the latter's concentration over a 24-h period. To maintain sample integrity, all plasma samples should be fortified with ascorbic acid and kept frozen prior to analyses.
双胺三嗪和米托蒽醌是两种新型蒽衍生物，它们对多种动物肿瘤以及在人类I期和II期临床试验中均显示出显著的抗肿瘤活性。我们已开发出一种快速、简单且灵敏的样品净化程序以及针对这两种药物的高效液相色谱（HPLC）测定法。该方法使用带有C18反相填料的市售微型柱，在进行HPLC分析之前从生物基质中分离出药物。对于这两种药物，该测定法的平均回收率为98±6%，变异系数（C.V.）小于7%。使用这种新方法，我们对双胺三嗪的测定灵敏度提高到了小于10 ng/ml，对米托蒽醌的测定灵敏度提高到了1 ng/ml，这使我们能够记录双胺三嗪和米托蒽醌延长的终末相血浆半衰期。平衡透析研究表明这两种药物都与蛋白质高度结合。米托蒽醌在人血浆中似乎比双胺三嗪更不稳定。在25℃和37℃下孵育24小时后，米托蒽醌从血浆中的回收率分别为40%和20%，双胺三嗪的回收率分别为90%和85%。在37℃下将米托蒽醌与人血浆一起孵育之前加入抗坏血酸，在24小时内其浓度下降不到10%。为保持样品完整性，所有血浆样品在分析前都应加入抗坏血酸并冷冻保存。
