de Vries A J, Nooter K
Institute of Applied Radiobiology and Immunology TNO, Rijswijk, The Netherlands.
J Chromatogr. 1991 Feb 15;563(2):435-42. doi: 10.1016/0378-4347(91)80053-f.
An analytical method for the determination of mitoxantrone in bone marrow was developed using high-performance liquid chromatography with electrochemical detection. The extraction procedure was optimized by investigating several factors which potentially could influence the recovery of mitoxantrone from bone marrow cells. The mean recovery of mitoxantrone from rat bone marrow was found to be 81.7% with a coefficient of variation 3.8%. High-performance liquid chromatography was carried out to quantitate mitoxantrone using ametantrone as internal standard. The detection limit of our analytical method amounts to 100 pg on-column, corresponding to 1 ng/ml of cell suspension containing 2 x 10(7) cells and a day-to-day variation of maximally 8%. Storage of bone marrow samples, containing mitoxantrone, for one to fourteen days resulted in a mean recovery of 94%, as compared to freshly analysed samples. Subsequently we studied the pharmacokinetics of mitoxantrone in rat bone marrow. It appeared that after an intravenous bolus injection of mitoxantrone (2.5 mg/kg) in rats, the drug accumulated in the femoral bone marrow for about four days, and thereafter gradually declined.
建立了一种采用高效液相色谱-电化学检测法测定骨髓中米托蒽醌的分析方法。通过研究几个可能影响米托蒽醌从骨髓细胞中回收率的因素，对提取程序进行了优化。发现米托蒽醌从大鼠骨髓中的平均回收率为81.7%，变异系数为3.8%。采用高效液相色谱法，以阿霉素为内标对米托蒽醌进行定量。我们分析方法的检测限为柱上100 pg，相当于含有2×10⁷个细胞的细胞悬液中1 ng/ml，且每日最大变化为8%。与新鲜分析的样品相比，含有米托蒽醌的骨髓样品储存1至14天的平均回收率为94%。随后，我们研究了米托蒽醌在大鼠骨髓中的药代动力学。结果表明，大鼠静脉推注米托蒽醌（2.5 mg/kg）后，药物在股骨骨髓中蓄积约4天，此后逐渐下降。
