Hadidi A H, Idle J R
Department of Pharmacology and Toxicology, St. Mary's Hospital Medical School, London, U.K.
J Chromatogr. 1988 May 13;427(1):121-30. doi: 10.1016/0378-4347(88)80110-5.
A novel method for the quantitative determination of the anti-cancer drug cyclophosphamide and its principal urinary metabolites 4-oxocyclophosphamide, carboxyphosphamide, phosphoramide mustard and bis(2-chloroethyl)amine has been devised. The assay combines adsorption of drug-related material onto Amberlite XAD-2 and thin-layer chromatography with spot visualization using 4-(4-nitrobenzyl)pyridine, rapid photography and densitometry. The intra-assay coefficient of variation for each compound was less than 6%. The limit of detection of the assay was 1 microgram ml-1 for cyclophosphamide, phosphoramide mustard and bis(2-chloroethyl)amine and 0.5 microgram ml-1 for 4-oxocyclophosphamide and carboxyphosphamide. The method was validated for cyclophosphamide and 4-oxocyclophosphamide using gas chromatography. It is concluded that the method provides the first means of determining the full metabolic spectrum for cyclophosphamide in patients without recourse to the administration of radioisotopically labelled drug.
已设计出一种定量测定抗癌药物环磷酰胺及其主要尿液代谢产物4-氧代环磷酰胺、羧磷酰胺、磷酰胺氮芥和双（2-氯乙基）胺的新方法。该测定方法将与药物相关的物质吸附到Amberlite XAD-2上，并结合薄层色谱法，使用4-（4-硝基苄基）吡啶进行斑点可视化、快速摄影和光密度测定。每种化合物的测定内变异系数小于6%。该测定方法对环磷酰胺、磷酰胺氮芥和双（2-氯乙基）胺的检测限为1微克/毫升，对4-氧代环磷酰胺和羧磷酰胺的检测限为0.5微克/毫升。该方法使用气相色谱法对环磷酰胺和4-氧代环磷酰胺进行了验证。得出的结论是，该方法首次提供了一种在不使用放射性同位素标记药物的情况下测定患者中环磷酰胺完整代谢谱的方法。
