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Biomedical subjects

C Fenselau

Publications and source records attributed to C Fenselau.

At least 109 records · Page 6Linked to original sources
PubMed1982

Comparison of biological-derived and synthetic leukotriene C4 by fast atom bombardment mass spectrometry.

The development of the technique of fast atom bombardment mass spectrometry (FAB-MS) has greatly expanded the capability to analyze non-volatile, complex biochemicals. The structure of leukotriene C4, a slow reacting substance of anaphylaxis, has recently been postulated as 6-glutathionyl-5-hydroxy-7,9,11,14-eicosatetraenoic acid. Even though LTC4 has been synthesized, it has not been possible to obtain direct mass spectrometric confirmation of this structure. FAB-MS has indicated that the biological LTC4 had a molecular weight of 625, identical to that of synthetic LTC4. The abundance of cationized species with one and two sodium atoms was the major difference between these leukotrienes which is probably a result of the difference in salt content of the purified molecules.

Mass Spectrometry↗
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

The effects of heating rate and sample size on the direct exposure/chemical ionization mass spectra of some biological conjugates.

A direct exposure probe has been used to obtain mass spectra of underivatized guanosine, deoxyguanosine, sucrose and the p-nitrophenyl-beta-D-glucuronide. In all cases, a protonated molecular ion is produced with good relative abundance. The effects of heating rate and sample size on the production of the [MH]+ ION ARE EXAMINED IN DETAIL FROM TOTAL ION ANd single ion currents produced during rapid, repetitive scanning of the spectra after probe insertion. From this data we conclude that protonated molecular ions are produced as a result of the enhanced volatility of neutral molecules on the probe surface, followed by chemical ionization, and not by surface ionization.

Deoxyguanosine↗
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

Mandelonitrile beta-glucuronide: synthesis and characterization.

Mandelonitrile beta-glucuronide, the compound patented as Laetrile, has been synthesized from rabbit liver uridine diphosphate-glucuronosyl transferase immobilized on beaded sepharose, has been analyzed by thin-layer chromatography, nuclear magnetic resonance, and gas chromatography-mass spectrometry, and has been tested for cytotoxicity and mutagenic activity with Salmonella typhimurium strains TA 98 and TA 100. Several commercial laetrile preparations contained no glucuronide; they contained amygdalin and neoamygdalin instead. Mandelonitrile, mandelonitrile glucuronide, and a mixture of amygdalin and neoamygdalin were each found to be mutagenic.

Amygdalin↗
PubMed1977

Synthesis and characterization of glucuronides of Cannabinol, cannabidiol, delta9-tetrahydrocannabinol and delta8-tetrahydrocannabinol.

Partially purified glucuronyltransferase immobilized on beaded sepharose has been used to synthesize the glucuronide conjugates of cannabinol, cannabidol, delta9-tetrahydrocannabinol and delta8-tetrahydrocannabinol. Trimethylsilylated methyl esters and per(trimethylsilyl) derivatives of these conjugates have been characterized by their gas chromatographic retention times and their electron impact and ammonia chemical ionization mass spectra.

Cannabidiol↗
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

Immobilized glucuronosyltransferase for the synthesis of conjugates.

Partially purified rabbit liver UDPglucuronosyltransferase is immobilized on agarose by the cyanogen bromide activation method. Both soluble and matrix-bound enzyme preparations display very similar Km and pH optimum. The storage stability of the immobilized enzyme at 4 degrees is 5-10 times improved over the soluble preparations. The agarose-bound UDPglucuronosyltransferase is successfully used in the synthesis of p-nitrophenyl glucuronide in an overall yield of 50-70%. The matrix-bound enzyme is reusable over an extended period of time and offers an easy and convenient synthetic tool for various drug glucuronides.

Glucuronates↗
PubMed1976

Solid-phase synthesis of drug glucuronides by immobilized glucuronosyltransferase.

Rabbit liver glucuronosyltransferase immobilized on beaded agarose has been used to synthesize glucuronic acid conjugates of meprobamate, diethylstibestrol, bilirubin, borneol, benzioc acid, and p-nitrothiophenol. The immobilized enzyme exhibited a high degree of specificity for UDPGA as cofactor when p-nitrophenol is used as substrate. Other cofactors tested were less effective, all producing less than 10% conjugation relative to UDPGA. The effects on agarose-bound enzyme activity of a variety of cosolvents and emulsifiers have been studied. Ethanol, dimethyl sulfoxide, propylene glycol, and bovine serum albumin are among the cosolvents and emulsifiers which can be used within limited concentration ranges to sulubilize lipophilic substrates for conjugation. Concentrations of calcium and magnesium cations between 1.5 and 10.0mM were found to enhance glucuronosyltransferase activity of the immobilized enzyme.

Calcium↗
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↗
PubMed1976

Review of the metabolism and mode of action of cyclophosphamide.

A review of recent studies of the pharmacology of cyclophosphamide is presented. Particular attention is paid to the use of mass spectrometry in the identification of the active compound phosphoramide mustard as a circulating human metabolite of cyclophosphamide, the development of an assay method for cyclophosphamide, phosphoramide mustard, and nornitrogen mustard, and a demonstration that alkylation by phosphoramide mustard proceeds through a symmetrical aziridinium ion.

Alkylation↗
PubMed1975

Reaction of 1,3-bis(2-chloroethyl)-1-nitrosourea with synthetic polynucleotides.

The antitumor agent BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) was incubated with poly(C) and poly(G) in aqueous solution at 37 degrees and pH 7 to produce approximately 0.33 and 0.07% substitution, respectively. Under the same conditions, there was relatively little reaction with poly(A) and poly(U). Poylnucleotides reacted with [14C]BCNU were digested by chemical and enzymatic methods, and the derivative nucleotides were isolated by column chromatography. There were identified by a combination of ultraviolet and mass spectroscopy as 3-(beta-hydroxyethyl)CMP, 3,N4-ethano-CMP, and 7-(beta-hydroxy-ethyl)GMP. This would indicate that BCNU generates active two carbon fragments, probably chloroethyl carbonium ions, which are free to react with nucleotides. The production of these substituted bases may be important to the mechanism of action of the therapeutic nitrosoureas since they would probably alter the function of any nucleic acid which contained them.

Carmustine↗