Hu O Y, Chang S P, Song Y B, Chen K Y, Law C K
School of Pharmacy, National Defense Medical Centre, Taipei, Republic of China.
J Chromatogr. 1990 Nov 16;532(2):337-50. doi: 10.1016/s0378-4347(00)83783-4.
Mitoxantrone is an anthracene derivative that acts as a cytostatic in a variety of cancers. A quantitative analytical method has been established for the determination of mitoxantrone in plasma. The method employed C18 reversed-phase ion-pair chromatography with an isocratic mobile phase of 50.0% methanol in 10 mM phosphate buffer (pH 3.0) plus 0.09% 1-pentanesulphonic acid and ultraviolet detection. Sample preparation consisted of two extraction steps using same organic solvent system at different pH to remove plasma impurities efficiently. Potential adsorption of mitoxantrone onto glassware was considered. Silanization of all glassware with 5% dichlorodimethylsilane in chloroform increased the extraction recovery in plasma from 50 to 85% with high reproducibility. Mitoxantrone was unstable in human plasma. To maintain plasma sample integrity, each millilitre of sample should be fortified with 0.1 ml of 5% vitamin C (in citrate buffer) and kept frozen until analysis. Using this new method, the calibration curve of mitoxantrone in plasma in the range of interest (1-500 ng/ml) showed good linearity (r = 0.996) and precision (both between-day and within-day coefficients of variation less than 10%). The lower detection limit of this assay method was 1 ng. The application of this method allowed us to study the stability of mitoxantrone in plasma, and the pharmacokinetics of mitoxantrone in nasopharyngeal carcinoma patients receiving 12 mg/m2. The study revealed a prolonged terminal phase half-life for mitoxantrone.
米托蒽醌是一种蒽衍生物，在多种癌症中起细胞生长抑制剂的作用。已建立了一种测定血浆中米托蒽醌的定量分析方法。该方法采用C18反相离子对色谱法，流动相为等度洗脱，由10 mM磷酸盐缓冲液（pH 3.0）中50.0%的甲醇加0.09%的1-戊烷磺酸组成，并进行紫外检测。样品制备包括两个萃取步骤，使用相同的有机溶剂系统在不同pH值下进行，以有效去除血浆杂质。考虑了米托蒽醌在玻璃器皿上的潜在吸附。用5%二氯二甲基硅烷的氯仿溶液对所有玻璃器皿进行硅烷化处理，可使血浆中的萃取回收率从50%提高到85%，且重现性高。米托蒽醌在人血浆中不稳定。为保持血浆样品的完整性，每毫升样品应加入0.1 ml 5%的维生素C（柠檬酸盐缓冲液中）并冷冻保存直至分析。使用这种新方法，米托蒽醌在血浆中的校准曲线在感兴趣的范围内（1-500 ng/ml）显示出良好的线性（r = 0.996）和精密度（日间和日内变异系数均小于10%）。该测定方法的检测下限为1 ng。该方法的应用使我们能够研究米托蒽醌在血浆中的稳定性，以及接受12 mg/m2剂量的鼻咽癌患者体内米托蒽醌的药代动力学。研究显示米托蒽醌的终末相半衰期延长。
