title: The aqueous stability of bupropion.
abstract: In this study the aqueous stability of bupropion was determined and the pH-degradation profile was obtained. The effects of hydrogen ion, solvent and hydroxide ion concentration are discussed with particular emphasis on the kinetics of degradation of bupropion. Kinetics and degradation of bupropion were determined by HPLC-UV and LC-MS analysis both utilising high pH chromatographic methods. Degradation of bupropion in aqueous solutions follows first-order reaction kinetics. The pH-degradation profile was determined using non-linear regression analysis. The micro- and macro-reaction constants for degradation are presented. Bupropion was most stable in aqueous solutions below pH 5. Degradation was catalyzed by water but mainly by hydroxide ion on the unionised form of bupropion. The energy of activation for decomposition in aqueous solution pH 10.7 I=0.055 was determined to be 53 kJ mol(-1) with a frequency factor of 6.43 x 10(10)s(-1). The degradants of bupropion were positively identified and a mechanism of degradation is proposed. The inherent instability of bupropion above pH 5 has implications for its therapeutic use, formulation, pharmacokinetics and use during analysis and storage.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College, Dublin 2, Ireland. obyrnep@tcd.ie
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.forename: Robert
authors.initials: R
authors.lastname: Williams
authors.forename: John J
authors.initials: JJ
authors.lastname: Walsh
authors.forename: John F
authors.initials: JF
authors.lastname: Gilmer
mesh_terms: D016642:Bupropion / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: D012996:Solutions; D016642:Bupropion