Nicotinamide riboside chloride
Compositional guideline for 'Nicotinamide riboside chloride' permitted for use in listed medicines
Last updated
Name of the ingredient
Nicotinamide riboside chloride (AAN)
Synonyms
Nicotinamide riboside chloride
Definition of the ingredient
Nicotinamide riboside chloride is a single chemical moiety containing nicotinamide and ribose. It is a white to light brown powder that is produced by chemical synthesis and is isolated by centrifiugation.
Molecular formula: C11H15N2O5Cl
CAS Number: 23111-00-4
| Test | Method reference | Acceptance criteria |
|---|---|---|
| Description | ||
| Appearance | Visual | White to light brown powder |
| Characteristics | ||
| Solubility in Water | BP General Notices | ≥446.5 mg/mL |
| Melting Point | BP (Appendix V A) | 115 - 125°C |
| Water Content | Karl Fischer USP <921> | ≤1% w/w |
| Identification | ||
| NMR | NMR[1], [2], [3], [4] | Recorded NMR spectra must be in full agreement with the structure of nicotinamide riboside. The percentage of the α and β forms must be determined by comparing the integration of the peak for the anomeric proton for α-nicotinamide riboside (located at ~6.6 ppm with a J coupling value of 5.4 Hz in 1H NMR) and the peak for the β-nicotinamide riboside (located at ~6.3 ppm with a J coupling value of 4.4 Hz in 1H NMR). |
| Assay | ||
| Nicotinamide riboside chloride | HPLC-UV | ≥90% w/w |
| Test | Method reference | Acceptance criteria |
|---|---|---|
| Residual solvents | ||
| Acetone | USP<467> | ≤3000 ppm |
| Methanol | USP<467> | ≤1000 ppm |
| Acetonitrile | USP<467> | ≤50 ppm |
| Methyl tert-butyl ether | USP<467> | ≤500 ppm |
| Incidental metals and non-metals | ||
| Arsenic | USP<2232> | ≤1.0 ppm |
| Mercury | USP<2232> | ≤1.0 ppm |
| Cadmium | USP<2232> | ≤1.0 ppm |
| Lead | USP<2232> | ≤0.5 ppm |
| * The cadmium content in the specification is given as 1 ppm as an upper limit for the ingredient. In the finished product, the cadmium content must comply with the acceptance criteria set out in the United States Pharmacopoeia - National Formulary (USP-NF) general chapter '<2232> Elemental Contaminants in Dietary Supplements' | ||
| Other organic or inorganic impurities or toxins | ||
| Methyl acetate | USP<467> | ≤1000 ppm |
| Acetamide | GC-FID | ≤27 ppm |
| Acetic acid | GC-FID | ≤5000 ppm |
| Microbiology | ||
| Microbiology | USP<61>, USP<62> | Complies with USP<1111> |
Footnotes
| [1] | Syntheses of Nicotinamide Riboside and Derivatives: Effective Agents for Increasing Nicotinamide Adenine Dinucleotide Concentrations in Mammalian Cells; Yang, Tianle et al; Journal of Medicinal Chemistry, 50 (26), 6458-6461; 2007. |
|---|---|
| [2] | Stereoselective synthesis of nicotinamide β-riboside and nucleoside analogs; Franchetti, Palmarisa et al; Bioorganic & Medicinal Chemistry Letters, 14 (18), 4655-4658; 2004 |
| [3] | Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives; Makarov, Mikhail et al; Beilstein J. Org. Chem, 15, 401–430; 2019. |
| [4] | 4. Proton magnetic resonance study of the intramolecular association and conformation of the α- and β-pyridine mononucleotides and nucleosides; Oppenheimer, Norman et al; Biochemistry, 15 (18), 3981-3989; 1976. |
Key to abbreviations
BP = British Pharmacopeia
FID = Flame Ionisation Detection
GC = Gas Chromatography
HPLC = High Performance Liquid Chromatography
ISO = International Organisation for Standardisation
NMR = Nuclear Magnetic Resonance
USP = United States Pharmacopoeia
UV = Ultra-Violet
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