Stability and disposition studies of cyclophosphamide metabolites
Thesis/Dissertation
·
OSTI ID:6997543
The hydrolysis of phosphoramide mustard was investigated using HPLC, /sup 31/P NMR and GC-MS with specific deuterium labels. The hydrolysis of phosphoramide mustard in sodium phosphate buffers was found to follow apparent first-order kinetics. The rate of hydrolysis was temperature and pH dependent, being slower under acidic conditions. At pH values above the pKa of the phosphoramide mustard nitrogen, the major hydrolytic pathway was via the formation of the aziridinium ion, followed by nucleophilic attack. At pH values below its pKa, cleavage of the P-N bond predominated. The dispositions of phosphoramide mustard and nornitrogen mustard following iv injections were studied in rats using GC-MS stable isotope assays.
- Research Organization:
- University of Southern California, Los Angeles (USA)
- OSTI ID:
- 6997543
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKYLATING AGENTS
ANIMALS
BIOLOGICAL PATHWAYS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DECOMPOSITION
DEUTERIUM
DRUGS
ENDOXAN
GAS CHROMATOGRAPHY
HYDROGEN ISOTOPES
HYDROLYSIS
IMMUNOSUPPRESSIVE DRUGS
INJECTION
INTAKE
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
LYSIS
MAMMALS
MASS SPECTROSCOPY
METABOLISM
NMR SPECTRA
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
RATS
RODENTS
SEPARATION PROCESSES
SOLVOLYSIS
SPECTRA
SPECTROSCOPY
STABLE ISOTOPES
TEMPERATURE DEPENDENCE
TRACER TECHNIQUES
VERTEBRATES
59 BASIC BIOLOGICAL SCIENCES
ALKYLATING AGENTS
ANIMALS
BIOLOGICAL PATHWAYS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DECOMPOSITION
DEUTERIUM
DRUGS
ENDOXAN
GAS CHROMATOGRAPHY
HYDROGEN ISOTOPES
HYDROLYSIS
IMMUNOSUPPRESSIVE DRUGS
INJECTION
INTAKE
INTRAVENOUS INJECTION
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIQUID COLUMN CHROMATOGRAPHY
LYSIS
MAMMALS
MASS SPECTROSCOPY
METABOLISM
NMR SPECTRA
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
RATS
RODENTS
SEPARATION PROCESSES
SOLVOLYSIS
SPECTRA
SPECTROSCOPY
STABLE ISOTOPES
TEMPERATURE DEPENDENCE
TRACER TECHNIQUES
VERTEBRATES