Unambiguous and sensitive methods based on gas chromatography-chemical ionization mass spectrometry have been developed to quantitate Cyclophosphamide and two alkylating and cytotoxic metabolites, phosphoramide mustard and nornitrogen mustard. The levels of these materials have been determined in the plasma and urine of five patients receiving Cyclophosphamide, 60 or 75 mg/kg i.v. Peak plasma l...

Phosphoramide mustard has the DNA as its main target, while acrolein affects proteins. This data as well that of Slott & Hales (1987), indicates that phosphoramide mustard is toxic to the embryo, and acrolein to the yolk sac. Most anomalies caused by cyclophosphamide affect the face, and to a significant extent, its middle and inferior third: cleft palate; micrognatia; braquignatia and cleaved ...

An enantioselective pinacol rearrangement of functionalized (E)-2-butene-1,4-diols was developed. In the presence of a catalytic amount of a chiral BINOL-derived N-triflyl phosphoramide, these 1,4-diols rearranged to β,γ-unsaturated ketones in excellent yields and enantioselectivities. The formation of a chiral ion pair between the intermediary allylic cation and the chiral phosphoramide anion ...

PURPOSE Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma), autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively "target" delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell po...

Resistance of wood reacted in situ with phosphorus pentoxide-amine to the brown-rot fungus Gloeophyllum trabeum and white-rot fungus Trametes versicolor was examined. Wood reacted with either octyl, tribromo, or nitro derivatives were more resistant to both fungi. Threshold retention values of phosphoramide-reacted wood to white-rot fungus T. versicolor ranged from 2.9 to 13.3 mmol, while these...

Previous work showed that melphalan-induced mutations in the aprt gene of CHO cells are primarily transversions and occur preferentially at G-G-C sequences, which are potential sites for various bifunctional alkylations involving guanine N-7. To identify the DNA lesion(s) which may be responsible for these mutations, an end-labeled DNA duplex containing a frequent site of melphalan-induced muta...

In the asymmetric addition of allyltrichlorosilane to benzaldehyde, polystyrenes with chiral phosphoramide substituents as Lewis base catalysts showed up to 2.4 times better catalytic activity and 1.4 times higher enantioselectivity than the corresponding low-molecular-weight analogues.

Since cyclophosphamide is used by both oral and i.v. routes in the treatment of hematological and solid malignancies, we designed a randomized, crossover clinical trial to evaluate the pharmacokinetics of this anticancer agent after either administration route. Plasma levels of cyclophosphamide and its two cytotoxic metabolites, 4-hydroxycyclophosphamide and phosphoramide mustard, were determin...

The 0-24-h urinary metabolic profile of cyclophosphamide was inves tigated in a series of 14 patients with various malignancies receiving combination chemotherapy including i.v. cyclophosphamide. This was accomplished using combined thin-layer chromatography-photographydensitometry, which can quantitate cyclophosphamide and its four prin cipal urinary metabolites (4-ketocyclophosphamide, nor-ni...

Cyclophosphamide, a widely used anticancer agent, requires initial metabolic activation to 4-hydroxycyclophosphamide (4-OHCP) to elicit its activity. The rate of decomposition of cis-4-OHCP was much faster in plasma than in buffer at pH 7.4. This plasma activity was not affected by treatment with acid (pH 1.3) or heat (60 degrees C for 30 min). The activity was retained in the macromolecular fr...