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Urolithin A

Compositional guideline for Urolithin A permitted for use in listed medicines

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Description

Urolithin A is a synthetic version of urolithin A of the compound formed endogenously following consumption of ellagic acid and ellagitannins. Ellagitannins and ellagic acid are dietary polyphenols found in various fruits and berries (pomegranate, blackberries, camu-camu, strawberries, raspberries), nuts (walnuts, hazelnuts, acorns, chestnuts, pecans), muscadine grapes and oak-aged wines and spirits.

Urolithin A is manufactured via chemical synthesis:

  1. Chemical reaction between 2-bromo-5-hydroxybenzoic acid and resorcinol in the presence of sodium hydroxide and catalyst of cupric sulfate pentahydrate (copper (II) sulfate pentahydrate).
  2. Followed by protonation of the resulting di-or mono-sodium salt of Urolithin A and further purification by trituration in acetic acid.
  • Molecular formula: C13H8O4
  • CAS number: 1143-70-0
  • Molecular weight: 228.20
  • Chemical names: 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; 3,8-dihydroxybenzo[c] chromen-6-one
  • Chemical structure:
Image of the Urolithin A chemical structure
TestMethod referenceAcceptance criteria[1]
Characterisation
General properties
AppearanceVisual inspectionSolid powder
ColourVisual inspectionBeige to yellow
Identity
IRFT-IR1 (USP<197>)Observation of characteristic peaks at 3340, 3130,3090, 1700, 1615, 1470, 1340 cm-1.
NMR1H-NMR (USP<761>)

1H-NMR: Observation of signals at 6.71-10.1 ppm.

13C-NMR: Observation of signals at 123.8-109.8 ppm. 

MSHPLC2-MS (USP<736>)Observation of peak at retention time: 1.767 min 
Assay
Assay – HPLCHPLC2NLT 98.0%
Purity
Purity – HPLCHPLC2NLT 98.5%
Water content
 Water ContentKarl FisherNMT 1%
Impurities and incidental constituents
  • Residual Solvents
Acetic acidGC3NMT 5000 ppm
  • Elemental impurities
CdElemental Impurities-Procedures (USP-NF <233>)NMT 0.5 ppm
PbNMT 0.5 ppm
AsNMT 1.5 ppm
HgNMT 0.1 ppm
CuNMT 50 ppm
AlNMT 5 ppm
Other heavy metalsNMT 1 ppm
  • Other organic or inorganic impurities or toxins

3,11-dihydroxy-5H,9H-benzo[c]isochromeno[4,3-g]chromene-5,9-dione  

(AZX1)

HPLC2NMT 0.17%
Any other individual impurityHPLC2NMT 0.17%
Residue on IgnitionUSP<281>NMT 0.5%

Footnotes

  1. FT IR KBr disc, wavenumbers: 4000-650 cm-1, resolution 4 cm-1, number of scan 16 method

  2. HPLC Method: Column: Zorbax Eclipse Plus C18, 4.6 x 150 mm, 3.5 μm, Mobile Phase A: 0.05% TFA in H2O, Mobile Phase B: 0.05% TFA in ACN, Flow Rate 1.2 ml/min, Detection: VWD: 230 nm, Column Temperature: 40°C, Injection Volume: 7 μL, Acquisition Time: 28.0 minutes (including 8.0 minutes re-equilibration) 

  3. GC Method: Column: Restek Rtx-624 30 m x 0.32 mm, 1.8 μm film or equivalent, Injector. Mode: Constant Flow, Flow: 3.0 mL/min; Inlet: Injection Volume: 1.0μL, Mode: Split, Split Ratio: 50, Temperature 180°C, Carrier Gas: helium; Oven Ramp: Initial Temperature: 40°C, hold 2 minutes, Ramp: 10°C/minute to 220°C, hold 3 minutes., Run Time: 23 minutes: Detector: Temperature: 280°C, Air Flow: 350 mL/min, Hydrogen: 40 mL/min, Makeup Flow: 40 mL/min (combined). Approximate RT acetic acid = 6.7 minutes.

Abbreviations

  • ACN: Acetonitrile
  • CAS: Chemical Abstract Services
  • FT IR: Fourier transformed Infrared Spectroscopy
  • GC: Gas Chromatography
  • HPLC: High-Pressure liquid Chromatography
  • MS: Mass Spectrophotometry
  • RT: Retention Time
  • TFA: Trifluoroacetic Acid
  • USP-NF: United States Pharmacopeia and the National Formulary

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