van Belle S J, Schoemaker T J, Verwey S L, Paalman A C, McVie J G
J Chromatogr. 1985 Jan 11;337(1):73-80. doi: 10.1016/0378-4347(85)80009-8.
Mitoxantrone is one of the newer anthracenedione derivatives which has already been studied in phase I and II trials, where it has shown significant antitumor activity against a variety of human tumours. To determine the prolonged terminal half-life of mitoxantrone, we developed a sensitive high-performance liquid chromatographic method, providing a detection limit of 1 ng/ml of extracted serum. This system uses a C18 reversed-phase column. The mobile phase consists of a mixture of acetonitrile (30%, v/v) and an ammonium formate buffer (70%, v/v) with a pH of 2.7. Hexane sulphonic acid is added as an ion-pair former. Detection at a wavelength of 658 nm provides a highly selective system, showing no interfering peaks. Ametantrone, another anthracenedione derivative, is used as an internal standard. The extraction procedure for serum also uses hexane sulphonic acid in an ion-paired system. Because of the highly selective detection wavelength, urine samples can be injected without a sample clean-up procedure. This very sensitive method, combined with high selectivity and a fast and inexpensive serum clean-up procedure, has allowed us to document the prolonged terminal plasma half-life of mitoxantrone (levels of 2-5 ng/ml of plasma can still be detected six days after an intravenous infusion of 15 mg/m2 over 30 min). In urine an as yet unidentified metabolite was discovered.
米托蒽醌是一种较新的蒽二酮衍生物，已在I期和II期试验中进行了研究，在这些试验中它对多种人类肿瘤显示出显著的抗肿瘤活性。为了确定米托蒽醌延长的终末半衰期，我们开发了一种灵敏的高效液相色谱法，提取血清的检测限为1 ng/ml。该系统使用C18反相柱。流动相由乙腈（30%，v/v）和pH为2.7的甲酸铵缓冲液（70%，v/v）的混合物组成。加入己烷磺酸作为离子对试剂。在658 nm波长处检测提供了一个高选择性的系统，没有干扰峰。另一种蒽二酮衍生物氨茴蒽醌用作内标。血清的提取程序在离子对系统中也使用己烷磺酸。由于检测波长具有高选择性，尿液样品无需样品净化程序即可进样。这种非常灵敏的方法，结合高选择性以及快速且廉价的血清净化程序，使我们能够记录米托蒽醌延长的终末血浆半衰期（静脉输注15 mg/m² 30分钟后六天仍可检测到血浆水平为2 - 5 ng/ml）。在尿液中发现了一种尚未鉴定的代谢物。
