Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding

J Pharm Biomed Anal. 2021 Mar 20;196:113927. doi: 10.1016/j.jpba.2021.113927. Epub 2021 Jan 27.


To administer vitamin C (VC) with precision to patients with the coronavirus disease (COVID-19), we developed an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to assess plasma VC concentrations. 31 patients with COVID-19 and 51 healthy volunteers were enrolled. VC stability was evaluated in blood, plasma, and precipitant-containing stabilizers. A proportion of 7.7 % of VC was degraded in blood at room temperature (RT) (approximately 20-25 °C) at 1.5 h post administration with respect to the proportion degraded at 0.5 h, but without statistical difference. VC was stable in plasma for 0.75 h at RT, 2 h at 4 °C, 5 days at -40 °C, and 4 h in precipitant-containing stabilizer (2 % oxalic acid) at RT. The mean plasma concentration of VC in patients with COVID-19 was 2.00 mg/L (0.5-4.90) (n = 8), which was almost 5-fold lower than that in healthy volunteers (9.23 mg/L (3.09. 35.30)) (n = 51). After high-dose VC treatment, the mean VC concentration increased to 13.46 mg/L (3.93. 34.70) (n = 36), higher than that in healthy volunteers, and was within the normal range (6-20 mg/L). In summary, we developed a simple UPLC-MS/MS method to quantify VC in plasma, and determined the duration for which the sample remained stable. VC levels in patients with COVID-19 were considerably low, and supplementation at 100 mg/kg/day is considered highly essential.

Keywords: COVID-19; Oxalic acid; Stability; UPLC-MS/MS; Vitamin C.

Publication types

  • Clinical Trial
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Ascorbic Acid / blood*
  • Ascorbic Acid / pharmacology*
  • COVID-19 / blood*
  • COVID-19 / prevention & control*
  • Chromatography, High Pressure Liquid / methods
  • Dietary Supplements
  • Female
  • Humans
  • Male
  • Middle Aged
  • Plasma / chemistry
  • Reference Values
  • SARS-CoV-2 / pathogenicity
  • Tandem Mass Spectrometry / methods
  • Young Adult


  • Ascorbic Acid