Synthesis and hydrolytic behaviour of glycerol-1,2-diibuprofenate-3-nitrate, a putative pro-drug of ibuprofen and glycerol-1-nitrate

J Pharm Pharmacol. 2001 Mar;53(3):345-50. doi: 10.1211/0022357011775578.


Nitroxylated derivatives of non-steroidal anti-inflammatory drugs appear to offer protection against the gastrotoxicity normally associated with non-steroidal anti-inflammatory drugs, ostensibly via local production of nitric oxide. A diester of ibuprofen and glycerol-1-mononitrate has been prepared via the condensation of ibuprofen with 3-bromopropan-1,2-diol, followed by silver-(I)-nitrate-mediated nitroxylation. The release of ibuprofen from this diester has been studied in a simulated gastric fluid model with direct analysis by reverse-phase HPLC, using an acetonitrile-water (80%:20%) mobile phase containing trifluoroacetic acid (0.005%). n-Propyl ibuprofen was found to undergo pH-dependent hydrolysis, ranging from negligible hydrolysis at pH 5 to 52% hydrolysis at pH 3, over a 2-h period in this model. The ibuprofen-glycerol mononitrate diester was subjected to the most vigorous model hydrolytic conditions and was found to undergo 50 % hydrolysis during the study period. This study shows that pro-drugs of ibuprofen and glycerol mononitrate can be obtained, and can undergo degradation to the parent drugs under conditions simulating those likely to be encountered in the stomach.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Chromatography, High Pressure Liquid
  • Gastric Juice / chemistry
  • Hydrolysis
  • Ibuprofen / chemical synthesis*
  • Ibuprofen / chemistry
  • Magnetic Resonance Spectroscopy
  • Nitroglycerin / analogs & derivatives*
  • Nitroglycerin / chemical synthesis*
  • Nitroglycerin / chemistry
  • Prodrugs / chemical synthesis*
  • Prodrugs / chemistry
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared


  • Anti-Inflammatory Agents, Non-Steroidal
  • Prodrugs
  • glycerol-1,2-diibuprofenate-3-nitrate
  • glycerol-1-nitrate
  • Nitroglycerin
  • Ibuprofen