Assessing retinol stability in a hydroquinone 4%/retinol 0.3% cream in the presence of antioxidants and sunscreen under simulated-use conditions: a pilot study

Clin Ther. 2008 Mar;30(3):543-7. doi: 10.1016/j.clinthera.2008.03.010.


Background: Retinol (ie,vitamin A) is commonly used in dermatology as an adjunct to treat rhytids, acne,and dyschromia. However, vitamin A and many of its derivatives have poor photostability and are unstable in the presence of oxygen.

Objective: We aimed to assess the stability of retinol under simulated patient application conditions in a commercially available hydroquinone 4% cream containing retinol 0.3%, avobenzone (ultraviolet-A sunscreen), octinoxate (ultraviolet-B sunscreen), vitamins C and E (antioxidants), and moisturizers.

Methods: One gram of the preparation was applied as a thin film to the inside base of 4 groups of four 100-mL wide-mouthed beakers, incubated in a 37+/-2 degrees C water bath. Each experimental group consisted of 4 beakers for assays at 0.5,1,2,and 4 hours. The samples were exposed to varying combinations of full spectrum light and headspace gas (air or inert nitrogen gas [N2 ]). Retinol content was assayed via high-pressure liquid chromatography using a 1:9 water:methanol solvent system. The control group (group 5) was not exposed to full-spectrum light or headspace gas but served for comparative purposes.

Results: On exposure to light and room air, retinol stability was 94.4% at 0.5 hour, 94.8% at 1 hour, 92.4% at 2 hours, and 91.5% at 4 hours. The retinol contained in the preparation was stable for >or=4 hours. Samples exposed to light and N 2 gas demonstrated 96.5% and 91.3% stability at 0.5 hour and 4 hours exposure times, respectively. Samples that were not exposed to light had a stability of 99.2% (group 3, exposed to air) and 96.9% (group 4, exposed to N(2)) of the initial retinol present after 4 hours.

Conclusion: The retinol in the hydroquinone 4%/ retinol 0.3% cream with antioxidants and sunscreens underwent <10% degradation under simulated-use conditions, including exposure to UV light, oxygen, and body temperature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemistry
  • Antioxidants / radiation effects*
  • Chromatography, High Pressure Liquid
  • Drug Stability
  • Hydroquinones / chemistry
  • Hydroquinones / radiation effects*
  • Light
  • Ointments
  • Oxygen / chemistry
  • Photolysis
  • Pilot Projects
  • Sunscreening Agents / chemistry
  • Sunscreening Agents / radiation effects*
  • Temperature
  • Time Factors
  • Ultraviolet Rays*
  • Vitamin A / analysis
  • Vitamin A / chemistry*
  • Vitamin A / radiation effects*


  • Antioxidants
  • Hydroquinones
  • Ointments
  • Sunscreening Agents
  • Vitamin A
  • Oxygen
  • hydroquinone