title: Forced Degradation and Photodegradation Studies of Pyrrolo[3,4-c]pyridine-1,3-dione Derivatives as Analgesic Active Compounds Using HPLC, UV and IR Spectrometry, and HPLC/MS Methods.
abstract: The stress and accelerated tests as well as photostability analysis in solutions and the solid phase of three selected derivatives of pyrrolo[3,4-c]pyridine-1,3-dione were carried out according the International Conference on Harmonization guidelines. For observation of the degradation of tested compounds, the RP-HPLC method was used. The study included the effect of temperature, relative humidity, water, H+ and OH- ions, hydrogen peroxide, and light (6.0×10(6), 1.2×10(6) lux·h) on the stability of pyrrolo[3,4-c]pyridine-1,3-dione derivatives. Studies have shown that these derivatives are photolabile, extremely unstable in an alkaline medium, labile in an acidic medium, and stable in a neutral medium. Their sensitivity to oxidizing agents depends on the chemical structure. The shortening of the aliphatic chain leads to an increase in the sensitivity to hydrolytic and oxidizing factors. The presence of the 1,3,4-tetraisoquinoline group promotes an increase in the susceptibility to photodegradation. The introduction of a carbonyl group to the aliphatic chain and the tetrafluoromethyl group to the phenyl ring stabilizes the molecule in the case of hydrolysis and oxidation and also increases sensitivity to light. The analysis of observed photodegradation products using the HPLC-diode array detector, HPLC/MS, and UV and IR spectrometry techniques showed degradation targeted at the breaking of the pyrrolo[3,4-c]pyridine-1,3-dione, piperazine, and/or tetrahydroisoquinoline rings.
authors.affiliation: Poznan University of Medical Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 6 Grunwaldzka Str., 60-780 Poznań, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Muszalska
authors.forename: Michał P
authors.initials: MP
authors.lastname: Ciemniejewski
authors.forename: Monika A
authors.initials: MA
authors.lastname: Lesniewska
authors.forename: Dominika
authors.initials: D
authors.lastname: Szkatuła
authors.forename: Wiesław
authors.initials: W
authors.lastname: Malinka
mesh_terms: D000700:Analgesics / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D017408:Guidelines as Topic; D006358:Hot Temperature; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010782:Photolysis; D011725:Pyridines / Q000032:analysis*; D011758:Pyrroles / Q000032:analysis*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D000700:Analgesics; D011725:Pyridines; D011758:Pyrroles; D014867:Water; D006861:Hydrogen Peroxide