Evaluation of photostability and phototoxicity of esterified derivatives of ubiquinol-10 and their application as prodrugs of reduced coenzyme Q10 for topical administration

Biofactors. 2020 Nov;46(6):983-994. doi: 10.1002/biof.1678. Epub 2020 Oct 6.


Ubiquinol-10 (UqH-10), the fully reduced form of ubiquinone-10 (Uq-10, coenzyme Q10 ), is an antioxidant and is involved in energy production. However, physicochemical disadvantages, such as rapid oxidation, water-insolubility, photoinstability, and phototoxicity, limit its application. We previously reported that UqH-10 1,4-bis-N,N-dimethylglycinate improved the oxidation susceptibility and poor bioavailability of UqH-10 in rats. Herein, we evaluated the photochemical properties of UqH-esterified derivatives (N,N-dimethylglycinate, hemi-succinate, ethylsuccinate, and hemi-glutarate). Photostability was examined by irradiation using artificial sunlight and monochromatic light. The concentration of each compound was determined using LC-MS/MS. Phototoxicity was assessed by singlet oxygen and superoxide assays. Delivery of UqH-10 via UqH-esters to the HaCaT human keratinocyte cell line was determined using LC-MS/MS. UqH-esters showed higher photostability to artificial sunlight than Uq-10 and UqH-10. Uq-10 and UqH-10 were rapidly degraded by monochromatic light at 279 nm, whereas UqH-esters were more stable. UVA and/or UVB irradiation generated high levels of singlet oxygen and superoxide in Uq-10, whereas UqH-esters were unreactive. Additionally, UqH-esters effectively delivered UqH-10 to HaCaT cells following efficient uptake in their ester forms and ester bond hydrolysis in the cells. In conclusion, UqH-ester derivatives exhibit higher photostability and lower phototoxicity compared with Uq-10 and UqH-10.

Keywords: coenzyme Q; drug delivery; keratinocyte; photostability; phototoxicity; prodrug; skin; ubiquinol.

MeSH terms

  • Administration, Topical
  • Antioxidants / administration & dosage
  • Antioxidants / metabolism*
  • Cells, Cultured
  • Humans
  • Keratinocytes / drug effects
  • Light / adverse effects*
  • Prodrugs / administration & dosage
  • Prodrugs / metabolism*
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / metabolism


  • Antioxidants
  • Prodrugs
  • Ubiquinone
  • ubiquinol-10
  • coenzyme Q10