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Rapid quantitation of cyclophosphamide metabolites in plasma by liquid chromatography–mass spectrometry

2006; Elsevier BV; Volume: 835; Issue: 1-2 Linguagem: Inglês

10.1016/j.jchromb.2006.03.022

1873-376X

Thomas F. Kalhorn, William N. Howald, Scott Cole, Brian Phillips, Joanne Wang, John T. Slattery, Jeannine S. McCune,

Acute Lymphoblastic Leukemia research

A method is described for the quantification of two metabolites of cyclophosphamide, specifically 4-hydroxycyclophosphamide (HCy), and carboxyethylphosphoramide mustard (CEPM). Plasma HCy is derivatized to the phenylhydrazone which is quantitated by LC–MS monitoring the chloride adduct of the derivative. The LLOQ based on material applied to the system is ∼20 fmol. Plasma CEPM concentration is determined using LC–MS with a deuterated internal standard. Both assays have 50-fold dynamic range and require less than 4 h to complete. The development of this rapid analytical method makes it feasible to adjust the dose of cyclophosphamide based on the pharmacokinetic disposition of HCy and CEPM in hopes of decreasing nonrelapse mortality in cancer patients.