THE DETERMINATION OF CYCLOPHOSPHAMIDE AND ITS METABOLITES IN BLOOD-PLASMA AS STABLE TRIFLUOROACETYL DERIVATIVES BY ELECTRON-CAPTURE CHEMICAL-IONIZATION GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

被引:26
作者
MOMERENCY, G
VANCAUWENBERGHE, K
SLEE, PHTJ
VANOOSTEROM, AT
DEBRUIJN, EA
机构
[1] UNIV ANTWERP,DEPT CHEM,B-2610 ANTWERP,BELGIUM
[2] UNIV ANTWERP,DEPT MED,CANC RES LAB,B-2610 ANTWERP,BELGIUM
关键词
D O I
10.1002/bms.1200230306
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
A method is described for the determination of the antitumour drug cyclophosphamide and six stable metabolites in plasma of cancer patients, namely dechloroethyl-cyclophosphamide, 4-keto-cyclophosphamide, carboxyphosphamide, alcophosphamide, nor-nitrogen mustard and the N-chloroethyl-1,3-oxazolidine-2-one, as methyl and/or trifluoroacetyl derivatives by single ion monitoring gas chromatography/mass spectrometry, mostly in the electron capture chemical ionization mode. The isolation of most metabolites was performed by solid-phase C-18 extraction in weakly acidic medium. The phosphoramide mustard isolated under these conditions decomposes readily to the nor-nitrogen mustard during derivatization. The original nor-nitrogen mustard and the chloroethyl-1,3-oxazolidine-2-one were isolated by liquid extraction with ethyl acetate in alkaline medium. Recoveries of 75-99% were measured using spiked blank plasma samples. Quantitation of metabolites in patient plasma samples was performed using two sets of calibration curves for the concentration ranges of 1-100 ng and 0.1-10 mu g of metabolite per millilitre of original plasma.
引用
收藏
页码:149 / 158
页数:10
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