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Biomedical subjects

M Colvin

Publications and source records attributed to M Colvin.

At least 73 records · Page 4Linked to original sources
PubMed1980

Quantitation by gas chromatography-chemical ionization-mass spectrometry of phenylalanine mustard in plasma of patients.

An unambiguous and sensitive method based on gas chromatography-chemical ionization-mass spectrometry has been developed to quantitate L-phenylalanine mustard and has been applied to measure levels in plasma of five patients receiving 0.15 to 0.25 mg/kg (10 to 17 mg) of the drug p.o. Peak plasma levels of 50 to 190 ng/ml were found to occur between 0.7 and 2.3 hr after ingestion. The time for the plasma level to fall to one-half of the peak value varied from 0.6 to 3 hr, and very low levels (less than 2 ng/ml) were present by 24 hr.

Adenocarcinoma↗
PubMed1979

Comparative effects of cyclophosphamide, isophosphamide, 4-methylcyclophosphamide, and phosphoramide mustard on murine hematopoietic and immunocompetent cells.

The effects of equimolal doses of cyclophosphamide (CY), isophosphamide (IP), 4-methylcyclophosphamide (4-MCY), and phosphoramide mustard (PM) on murine hematopoietic spleen colonies and adoptively transferred antibody-forming cells in vivo were compared. Equimolal doses of the drugs produced significantly different effects. All the drugs exerted an increasing effect against the ability of adoptively transferred immunocompetent cells to produce a significant anti-sheep red blood cell titer as the length of time between cell transfer and drug administration was increased. The maximum effect was seen when a drug was given 48--72 hours after antigen and spleen cell transfer. CY and IP produced significantly greater immunosuppressive effects than did the other drugs at all times after cell transfer and at all doses administered. PM had the least immunosuppressive effect at each dose evaluated. Against hematopoietic spleen colonies, the cytotoxic effects of 4-MCY and PM were similar and, at most doses studied, significantly greater than the effect of either CY or IP. Inasmuch as PM is an active metabolite of CY, it appeared either that one of the prior metabolites of CY was responsible for this marked immunosuppressive effect or that due to differences in polarity, PM was differentially distributed within the two cell systems as compared to CY. The differences in hematopoietic effects among all drugs were much less than those seen against immunocompetent cells and were not dependent on time of drug administration.

Animals↗
PubMed1979

Comparison of mutagenicity, antitumor activity, and chemical properties of selected nitrosoureas and nitrosoamides.

A number of nitrosoureas and nitrosoamides have been compared with respect to mutagenicity for Salmonella typhimurium, in vitro cytotoxicity, in vivo toxicity and antitumor activity against murine L1210 leukemia, and chemical properties. Despite chemical similarities between the nitrosoureas and nitrosoamides, they show important differences in biological activity. Some of the nitrosoureas are very active antitumor agents, and they are less mutagenic than are the corresponding nitrosoamides, which lack antitumor activity.

Animals↗
PubMed1978

Quantitation by gas chromatography-chemical ionization mass spectrometry of cyclophosphamide, phosphoramide mustard, and nornitrogen mustard in the plasma and urine of patients receiving cyclophosphamide therapy.

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 levels of phosphoramide mustard of 50 to 100 nmoles/ml were found at 3 hr after cyclophosphamide administration. Variable levels of nornitrogen mustard were found in the plasma. This product may be arising in part from the decomposition of other metabolites during sample storage and preparation.

Adolescent↗
PubMed1977

Identification of aldophosphamide as a metabolite of cyclophosphamide in vitro and in vivo in humans.

Aldophosphamide (NSC 254), a putative key metabolite of cyclophosphamide, has now been isolated as a cyanohydrin derivative from an incubation mixture of cyclophosphamide with mouse liver microsomes in vitro and from the plasma of a cyclophosphamide-treated patient. The cyanohydrin has been shown to be identical with an authenic synthetic sample by mass spectrometry and combined gas chromatography-mass spectrometry.

Aldehydes↗
PubMed1976

Chemistry of nitrosoureas. Decomposition of Deuterated 1,3-bis(2-chloroethyl)-1-nitrosourea.

BCNU-alpha-d4 [1,3-bis(2-chloro-1,1-dideuterioethyl)-1-nitrosourea] and BCNU-beta-d4 [1,3-bis(2-chloro-2,2-dideuterioethyl)-1-nitrosourea] were synthesized and decomposed in buffered (pH 7.4)water. The products were analyzed by GC-MS. The deuterium distribution in the products is inconsistent with vinylcarbonium ion or diazochloroethane intermediacy but is consistent with a 2-chloroethylcarbonium ion intermediate with some rearrangement to the 1-chloroethylcarbonium ion and the cyclic chloronium ion.

Carmustine↗
PubMed1976

Alkylating properties of phosphoramide mustard.

The relative alkylating activities of two of the cytotoxic metabolites of cyclophosphamide, phosphoramide mustard and nornitrogen mustard, have been studied at pH 4.6 and 7.4. The products formed on alkylation of ethanethiol by these metabolites have been identified, confirming that phosphoramide mustard undergoes alkylation reactions as an intact molecule. Deuterated analogs of the two metabolites have been synthesized, namely N,N-bis(2,2-dideutero-2-chloroethyl)-phosphorodiamidic acid and N,N-bis(2,2-dideutero-2-chloroethyl)amine and used to determine that alkylation proceeds directly via an aziridinium intermediate rather than a direct SN2 displacement of the chlorine atom.

Alkylation↗
PubMed1976

Approaches to the pharmacokinetics of cyclophosphamide (NSC 26271): Quantitation of metabolites.

Recent evidence has implicated phosphoramide mustard as a highly active metabolite of cyclophosphamide (CP). This compound has been shown to be produced from CP both in vitro and in vivo. To further study the role of this active metabolite we have devised methods to quantitate the compound in human serum and urine using gas chromatography-chemical ionization mass spectrometry. Tetradeuterated phosphoramide mustard has been synthesized and is used as an internal standard. CP and nor-nitrogen mustard have also been quantitated in human samples using analogous tetradeuterated internal standards.

Chromatography, Gas↗