Malet-Martino M, Gilard V, Martino R
Biomedical NMR Group, IMRCP Laboratory, Université Paul Sabatier, 118, route de Narbonne, TOULOUSE, France.
Curr Pharm Des. 1999 Aug;5(8):561-86.
Cyclophosphamide (CP) has been in clinical use for the treatment of malignant disease for over 40 years. CP is inactive until it undergoes complex metabolic pathways leading to the ultimate alkylating agent, phosphoramide mustard, but also to inactive and toxic metabolites. Sensitive and specific methods are now available for the measurement of CP and its enantiomers, its metabolites and their stereoisomers, in biological matrices. An overview is given of the methods of analysis of CP and its metabolites described in literature since 1993 as well as the current knowledge about its metabolism. Five classes of methods are described: (1) thin-layer chromatography-photographic densitometry, (2) high performance liquid chromatography, (3) gas chromatography and gas chromatography coupled to mass spectrometry, (4) phosphorus-31 nuclear magnetic resonance and (5) enantiomeric separation. In each case, sample clean up and preparation are described. Precision and limits of quantification of the assays are indicated. A table summarizes all the analytical methods for assaying each metabolite.
环磷酰胺(CP)已在临床用于治疗恶性疾病40多年。CP在经历复杂的代谢途径产生最终的烷化剂磷酰胺氮芥之前是无活性的,但同时也会产生无活性和有毒的代谢产物。现在已有灵敏且特异的方法用于测定生物基质中环磷酰胺及其对映体、代谢产物及其立体异构体。本文综述了自1993年以来文献中描述的环磷酰胺及其代谢产物的分析方法以及关于其代谢的现有知识。描述了五类方法:(1)薄层色谱 - 光密度法,(2)高效液相色谱法,(3)气相色谱法和气相色谱 - 质谱联用,(4)磷 - 31核磁共振法,(5)对映体分离法。每种方法都描述了样品净化和制备过程。指出了测定方法的精密度和定量限。一个表格总结了测定每种代谢产物的所有分析方法。