Cox P J, Farmer P B
Chem Biol Interact. 1975 Feb;10(2):103-14. doi: 10.1016/0009-2797(75)90104-0.
Cyclophosphamide is not structurally modified by blood plasma and may be recovered quantitatively from it. The apparent loss of alkylating ability of cyclophosphamide, as measured by its ability to react with 4-(p-nitrobenzyl)-pyridine (NBP), following treatement with plasma is not, as has been reported, due to metabolism of the drug but rather to an inhibition of the colorimetric reaction by a constituent of the plasma. This inhibition is strongly pH dependent, reaching 100% when the pH of the solution of cyclophosphamide in plasma is above 8, and falling to less than 20% when the pH is below 6, but extraction with chloroform at pH 7 separates cyclophosphamide from the inhibitor. Although the nature of the inhibitor has not been elucidated, its presence in plasma is of great importance in the quantitative determination of cyclophosphamide, and may also be of significance in the biological effects of cyclophosphamide and other alkylating agents in vivo.
环磷酰胺在血浆中不会发生结构修饰，并且可以从血浆中定量回收。用血浆处理后，通过环磷酰胺与4-(对硝基苄基)-吡啶（NBP）反应的能力来衡量，环磷酰胺烷基化能力的明显丧失，并非如报道的那样是由于药物代谢，而是由于血浆中的一种成分对比色反应的抑制。这种抑制强烈依赖于pH值，当血浆中环磷酰胺溶液的pH值高于8时，抑制率达到100%，而当pH值低于6时，抑制率降至20%以下，但在pH值为7时用氯仿萃取可将环磷酰胺与抑制剂分离。尽管抑制剂的性质尚未阐明，但其在血浆中的存在对环磷酰胺的定量测定非常重要，并且在环磷酰胺和其他烷基化剂在体内的生物学效应中也可能具有重要意义。
