Stability of new analgesic active compound, pyrrolo-[3,4-c]pyridine derivative, in aqueous solutions.
The kinetics of hydrolysis of 4-ethoxy-2-[2-hydroxy-3-(4-phenyl-1-piperazinyl)]propyl-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo[3,4-c]pyridine (III) in aqueous solutions at 333, 343, 353 and 363 K over the pH range 0.4-5.0 was investigated. The decomposition was observed by means of the HPLC method. A sample solution was chromatographed on octadecyl-packed column (LiChrosorb 100 RP-18 column 250 x 4.0 mm I.D., dp 5 microm) using a mixture of acetonitrile and phosphate buffer (pH 2, 0.01 mol/L) as an eluent (45:55, v/v--phase A or 30:70, v/v--phase B). The UV detection was performed at a wavelength of 239 nm. The stability of compound III was found to be dependent on pH. The pH-rate profile indicated specific acid- and base-catalyzed reactions as well as spontaneous water-catalyzed degradation. The ionic strength effect, the pKa value (2.9; 6.0), the pHmin value (2.1) and thermodynamic parameters of the reaction (energy of activation (Ea), enthalpy (DeltaH(not equal to)) and entropy (DeltaS(not equal to were determined.
Department of Pharmaceutical Chemistry, Poznań University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland. imuszals@amp.edu.pl
Izabela
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Muszalska
Eliza
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Wojtyniak
D000700:Analgesics / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007094:Imides / Q000737:chemistry*; D007700:Kinetics; D009994:Osmolar Concentration; D011725:Pyridines / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
C529785:4-ethoxy-2-(2-hydroxy-3-(4-phenyl-1-piperazinyl))propyl-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo(3,4-c)pyridine; D000700:Analgesics; D007094:Imides; D011725:Pyridines