PGE1 metabolism by the perfused rat liver.

The hepatic and biliary metabolites of PGE1 have been isolated and identified after infusions of PGE1 into isolated rat liver preparations. The results demonstrate that in general PGE1 undergoes metabolism similar to that of PGE2 in the rat and reveals the possibility of a selective PG metabolite transport system across the biliary canalicular membrane.

Structural verification of 15-oxo-13,14-dihydrothromboxane B2.

The mass spectra of three stable isotope derivatives are presented to confirm ion assignments in the spectrum of the methoxime, trimethylsilyl ether, methyl ester from 15-oxo-13,14-dihydrothromboxane B2.

Modification of prostaglandin and thromboxane release by immunological sensitisation and successive immunological challenges from guinea-pig lumg.

The release of prostaglandins (PGs) and thromboxanes (Txs) from perfused guinea pig lungs was investigated during different immunological states. The major product released from normal lungs perfused with exogenous arachidonic acid was 6-oxo-PGF1a. The procedure of sensitisation to specific antigen resulted in an increase in the release of 15-oxo-13,14-dihydro-TxB2 and a decrease in the release of 6-oxo-PGF1a- and 6,15-dioxo-13,14-dihydro-PGF1a from lungs perfused with arachidonic acid. The relative amount of 15-oxo-13,14-dihydro-TxB2 released progressively increased with the number of immunological challenges with both exogenous and endogenously derived substrate, arachidonic acid. This change in response to successive immunological challenges may represent a protective mechanism to prevent parent Txs and PGs entering the systemic circulation.

Mass spectral characterization of 6-oxo-OGF.

The mass spectra of eleven derivatives are presented to provide structural support for the recently discovered prostaglandin, 6-oxo-PGF1alpha, which we have isolated from incubations of arachidonic acid with ram seminal vesicles or released during isolated perfusions of sensitized guinea pig lungs.

Limitations of diazomethane for the quantification of 15-oxo-prostaglandin F2alpha.

The relatively rapid formation of pyrazoline adducts is a serious side reaction in the esterification of 15-oxo-PGF2alpha with ethereal diazomethane under conditions used routinely in the chemical derivatization of prostaglandins.

The identification of two novel prostaglandins and a thromboxane.

6,15-Dioxo-PGF1alpha, 6,15-dioxo-13,14-dihydro-PGF1alpha and 15-oxo-thromboxane B2 have been identified in incubates of ram seminal vesicle homogenates with added arachidonic acid or in the perfusate from sensitised challenged guinea pig lungs. These compounds are probably related to 6-oxo-PGF1alpha and thromboxane B2. The structures have been determined by gas chromatography mass spectrometry, following suitable chemical derivatisation.

The pharmacology of prostaglandin-like substances released from guinea-pig lungs during anaphylaxis.

The pharmacology of the prostaglandins (PGs) and thromboxanes (Txs) released from immunologically challenged guinea-pig lungs is related to their roles in the anaphylactic response. 6-oxo-PGF1alpha probably contibutes substantially to bronchoconstriction during anaphylaxis. TxB2 may contribute to the anaphylactic response by increasing SRA-A release and by stimulating leucotaxis. The 15-oxo metabolites of PGE2 and PGF2alpha are rather weak spasmogens, but might modify respiratory muscle contractions and pulmonary vascular resistance. The 15-oxo 13,14 dihydro metabolites of PGE2 PGF2alpha and TxB2 were inactive in the systems studied, suggesting an important inactivating role for the 13:14 reductase enzyme.

Analysis of isomeric impurities in a synthesis of the novel anti-inflammatory drug, benoxaprofen.

Gas-liquid chromatographic procedures are described for the determination of isomeric impurities in rho-chlorobenzoyl chloride and the intermediates, 2-(rho-nitrophenyl)-proprionitrile and 2-phenylpropionitrile, in a ten-stage synthesis of benoxaprofen, 2-(rho-chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid.

GLC and NMR analysis of isomeric impurities in the new anti-inflammatory agent benoxaprofen.

GLC and NMR methods are described for the determination of four possible isomeric impurities in the novel anti-inflammatory agent benoxaprofen. The 2- and 3-chlorophenyl isomers were determined by GLC after alkaline hydrolysis and subsequent methylation. A rapid NMR procedure, using the lanthanide shift reagent tris- (1, 1, 1, 2, 2, 3, 3-heptafluoro- 7, 7-dimethyl- 4, 6-octanedionato)-europium, was developed for the 6- and 7- (alpha-methylacetic acid) isomers. Similar methodolology, with tris-(3-heptafluorobutyryl-d-camphorato)europium, enabled the determination of the enantiomer ratio for benoxaprofen. For the positional isomers, the limits of detection were 0.05% by GLC and 0.2% by NMR.

Analysis of 1-(2-phenyladamant-1-yl)-2-methylaminopropane as its chlorodifluoroacetyl derivative.

The diastereoisomeric content of 1-(2-phenyladamant-1-yl)-2-methylaminopropane can be determined by gas chromatography following treatment with chlorodifluoroacetic anhydride. Racemisation occurs in the synthesis of 2-phenyladamantane from the corresponding 2-chloroadamantane in the Friedel-Crafts reaction with aluminium chloride, but fractionation of the diastereoisomers can occur in the purification steps. A method for determining 2-phenyladamantane in plasma and urine extracts at the nanogram level using an electron-capture detector is described and compared with a previously described radio-assay procedure.