ABSTRACT
HPLC-NMR, HPLC-MS, and HPLC-UV were used to characterize the predominant solution autoxidation and photodegradation products of ethynylestradiol (1). A hydroperoxide (2) and a series of isomeric dimeric oxidation products (3-7), were identified.
Subject(s)
Estradiol Congeners/analysis , Ethinyl Estradiol/analysis , Chromatography, High Pressure Liquid , Estradiol Congeners/chemistry , Ethinyl Estradiol/chemistry , Indicators and Reagents , Magnetic Resonance Spectroscopy , Mass Spectrometry , Oxidation-Reduction , Photochemistry , Spectrophotometry, UltravioletABSTRACT
High-performance liquid chromatography/mass spectrometry (HPLC/MS) was used to identify and elucidate key structural characteristics of a novel dual cyclooxygenase/lipoxygenase inhibitor, tepoxalin (3-[5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-pyrazolyl]-N-hydroxy- N-methylpropanamide), its synthesis-related byproducts in bulk drug substance, and degradation products stemming from probe stability studies. Such information is needed to assist in synthesis optimization and in the preparation of stable formulations for toxicity studies and clinical trials. High-performance liquid chromatography, in conjunction with mass spectrometry (HPLC/MS) and UV photodiode array detection, can often expedite the gathering of preliminary data that contribute to several aspects of the pharmaceutical development process.
Subject(s)
Immunosuppressive Agents/chemistry , Pyrazoles/chemistry , Chromatography, High Pressure Liquid , Time FactorsABSTRACT
Fast-atom bombardment-tandem mass spectrometry (FAB-MS-MS) was used to characterize the structure of atosiban, a synthetic oxytocin antagonist, and one of its synthesis-related impurities. The nature of the structural modification in the impurity of interest, replacement of the proline residue by 5-aminovaleric acid, was determined directly from its product ion MS-MS spectrum. Confirmation of the identity of the impurity was accomplished with GC-MS.
Subject(s)
Peptides/analysis , Vasotocin/analogs & derivatives , Amino Acids/analysis , Chemical Phenomena , Chemistry, Physical , Drug Contamination , Gas Chromatography-Mass Spectrometry , Spectrometry, Mass, Fast Atom Bombardment , Vasotocin/analysisABSTRACT
The degradation products of histrelin (1, less than Glu-His-Trp-Ser-Tyr-(D-Nim-bzl-His)-Leu-Arg-Pro-NHEt) were determined in aqueous solution at pH 5.4 and 87 degrees C over an 18-day period (47% degradation). These degradation products (2-5) resulted from the cleavage of less than Glu-His and Trp-Ser peptide bonds, His-Trp diketopiperazine formation, and racemization of serine and histidine residues.
Subject(s)
Gonadotropin-Releasing Hormone/analogs & derivatives , Amino Acid Sequence , Chromatography, High Pressure Liquid , Gonadotropin-Releasing Hormone/chemistry , Infusions, Parenteral , Molecular Sequence Data , SolutionsABSTRACT
The primary solution degradation products of the antiulcer drug etintidine (1, N"-cyano-N-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]ethyl]- N'-2-propynylguanidine) were determined to be the guanyl urea 2, the guanidine 3, the amine 4a, and the cyanoamine 4b. These products resulted from nitrile hydrolysis and/or intramolecular cyclization of the guanidino and propargyl groups. The amine 4a was found to be a predominant degradation product in aqueous media of pH 4-7 at 70 +/- 0.2 degrees C.
Subject(s)
Histamine H2 Antagonists/analysis , Imidazoles/analysis , Chromatography, High Pressure Liquid , Cyclization , Drug Residues/analysis , Hydrogen-Ion Concentration , Hydrolysis , Oxidation-Reduction , Spectrophotometry, UltravioletABSTRACT
The products of aqueous chlorination reactions of 1-methylnaphthalene, fluorene, dibenzofuran, anthracene, phenanthrene, 1-methylphenanthrene, fluoranthene, and pyrene have been determined. The conditions employed for these reactions approximated those that might be encountered in water treatment facilities. Reactions at pH greater than 6 tended to produce oxygenated products (epoxides, phenols, quinones, etc.), and reactions at pH less than 6 tended to produce both oxygenated (quinones) and chlorinated products.
