Аннотация:
Background: Nitroproston is a novel prostaglandin-based compound modified by NO-donating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. Objective: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products. Methods: The principal biodegradation products of Nitroproston were identified in vitro using liquid chromatography/ion trap – time-of-flight mass-spectrometry. The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by liquid chromatography/triple –stage quadrupole mass spectrom
Ключевые слова:
Asthma; LC-MS; Metabolism; Multi-target drugs; Nitroproston; Obstructive bronchitis; Prostaglandins
glycerol 1,3 dinitrate; nitroproston; prostaglandin A2; prostaglandin B2; prostaglandin derivative; prostaglandin E2; unclassified drug; prostaglandin E2; Article; biodegradation; blood sampling; drug degradation; drug half life; drug identification; drug stability; drug structure; human; in vitro study; incubation time; ion trap mass spectrometry; liquid chromatography-mass spectrometry; New Zealand White (rabbit); nonhuman; priority journal; rat; time of flight mass spectrometry; triple quadrupole mass spectrometry; analogs and derivatives; animal; chemistry; half life time; high performance liquid chromatography; Leporidae; liver microsome; metabolism; species difference; tandem mass spectrometry; Animals; Chromatography, High Pressure Liquid; Dinoprostone; Drug Stability; Half-Life; Humans; Microsomes, Liver; Rabbits; Rats; Species Specificity; Tandem Mass Spectrometry
Mesonzhnik N. V. Natal`ya Vladimirovna 1983-
Moskaleva N. E. Natal`ya Evgenyevna 1971-
Shestakova K. M. Kseniya Mikhaylovna 1992-
Kurynina K. O.
Baranov P. A. Pavel Andreevich 1984-
Gretskaya N. M.
Serkov I. V.
Lyubimov I. I.
Bezuglov V. V.
Appolonova S. A. Svetlana Aleksandrovna 1973-
Месонжник Н. В. Наталья Владимировна 1983-
Москалева Н. Е. Наталья Евгеньевна 1971-
Шестакова К. М. Ксения Михайловна 1992-
Курyнина К. О.
Баранов П. А. Павел Андреевич 1984-
Грецкайа Н. М.
Серков И. В.
Любимов И. И.
Безуглов В. В.
Апполонова С. А. Светлана Александровна 1973-
LC-MS/MS identification and structural characterization of main biodegradation products of nitroproston-A novel prostaglandin-based pharmaceutical compound
LC-MS/MS identification and structural characterization of main biodegradation products of nitroproston-A novel prostaglandin-based pharmaceutical...
Текст визуальный непосредственный
Drug Metabolism Letters
Vol.12, Issue1 P. 54-61
2018
Статья
Asthma LC-MS Metabolism Multi-target drugs Nitroproston Obstructive bronchitis Prostaglandins
glycerol 1,3 dinitrate nitroproston prostaglandin A2 prostaglandin B2 prostaglandin derivative prostaglandin E2 unclassified drug prostaglandin E2 Article biodegradation blood sampling drug degradation drug half life drug identification drug stability drug structure human in vitro study incubation time ion trap mass spectrometry liquid chromatography-mass spectrometry New Zealand White (rabbit) nonhuman priority journal rat time of flight mass spectrometry triple quadrupole mass spectrometry analogs and derivatives animal chemistry half life time high performance liquid chromatography Leporidae liver microsome metabolism species difference tandem mass spectrometry Animals Chromatography, High Pressure Liquid Dinoprostone Drug Stability Half-Life Humans Microsomes, Liver Rabbits Rats Species Specificity Tandem Mass Spectrometry
Background: Nitroproston is a novel prostaglandin-based compound modified by NO-donating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. Objective: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products. Methods: The principal biodegradation products of Nitroproston were identified in vitro using liquid chromatography/ion trap – time-of-flight mass-spectrometry. The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by liquid chromatography/triple –stage quadrupole mass spectrom