Przybylski M, Ringsdorf H, Lenssen U, Peter G, Voelcker G, Wagner T, Hohorst H J
Biomed Mass Spectrom. 1977 Aug;4(4):209-15. doi: 10.1002/bms.1200040404.
The hydroperoxy and several alkylthio derivatives of the antitumor agents cyclophosphamide (2-bis(2-chloroethyl)amino tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide), ifosfamide (3-(2-chloroethyl)-2-(2-chloroethylamino)tetrahydro-2H-1,3,1-oxazaphosphorine 2-oxide) and trofosfamide (3-(2-chloroethyl)-2-(bis(2-chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) were characterized by electron impact and field desorption mass spectrometry. The compounds, which are stabilized derivatives of the activated hydroxylated intermediates of cyclophosphamide (ifosfamide, trofosfamide), could be identified as 4-hydroperoxy and 4-alkylthio oxazaphosphorines. The existence of diastereomers of these products was demonstrated by thin-layer chromatography and f.d. mass spectra. Derivatization with benzylmercaptan was found to be an appropriate method for the quantitative isolation and mass spectral identification of the activated metabolic intermediates of cyclophosphamide from biological material. Using this reaction, 4-hydroxycyclophosphamide and its acyclic tautomer, aldophosphamide, which are too unstable for direct identification, were detected in urine and serum of patients treated with 3H-cyclophosphamide.
通过电子轰击和场解吸质谱法对抗肿瘤药物环磷酰胺（2-双（2-氯乙基）氨基四氢-2H-1,3,2-恶唑磷杂环己烷2-氧化物）、异环磷酰胺（3-（2-氯乙基）-2-（2-氯乙基氨基）四氢-2H-1,3,2-恶唑磷杂环己烷2-氧化物）和曲磷胺（3-（2-氯乙基）-2-（双（2-氯乙基）氨基）四氢-2H-1,3,2-恶唑磷杂环己烷2-氧化物）的氢过氧和几种烷硫基衍生物进行了表征。这些化合物是环磷酰胺（异环磷酰胺、曲磷胺）活化羟基化中间体的稳定衍生物，可鉴定为4-氢过氧和4-烷硫基恶唑磷杂环己烷。通过薄层色谱法和场解吸质谱证明了这些产物非对映异构体的存在。发现用苄硫醇衍生化是从生物材料中定量分离和质谱鉴定环磷酰胺活化代谢中间体的合适方法。利用该反应，在接受3H-环磷酰胺治疗的患者的尿液和血清中检测到了对直接鉴定来说过于不稳定的4-羟基环磷酰胺及其无环互变异构体醛磷酰胺。
