Compositional guideline: Ademetionine ('SAMe')
Definition
Ademetionine of non-recombinant biological or chemical synthetic origin, intended for use in encapsulated, tabletted or powdered nutritional supplements, comprises a mixture of the biologically-active (S),S-diastereoisomer and the biologically inactive (R)-S-diastereoisomer of S-adenosylmethionine, stabilised as salts with suitable anions. This material is also known by the trivial name 'SAMe' or 'SAM-e'. Anions typically include sulfate, tosylate or tosylate/sulfate, but may comprise any anion which confers stability on the 'SAMe' moeity and which is acceptable for use in therapeutic goods in Australia. The 'SAMe' salt may be a lyophilised or spray dried powder or may be stabilised by drying on a suitable inert matrix material such as silicon dioxide, mannitol or lactose.
Picrolonic acid must not be used in the manufacture of ademetionine.
Small amounts of the degradation products adenine, homoserine lactone, S-pentosylmethionine and methylthioadenosine may be present. The product may be microencapsulated to enhance stability and may include free flowing agents.
| Test | Min | Max | Typical | Method |
|---|---|---|---|---|
| (S)-S-adenosylmethionine as the free cation | 95% of label claim | 110% of label claim | 10-50% by weight | HPLC*§; 1H-NMR*‡; CZE*¶ |
| Identification of (S)-S-adenosylmethionine and (R)-S-adenosylmethionine | HPLC* by comparison to a reference standard | |||
| Identification of counter-ions | HPLC* by comparison to a reference standard | |||
| Ratio of (R),S-isomer to (S),S-isomer | (R)-S-isomer is to be not more than 40% relative to the (S),S-isomer | |||
| Moisture | - | 2.5% | Karl Fischer Method or USP<921> | |
| Solvent residues | Complies with limits for specific solvents in the ICH topic Q3C. | GC | ||
| Heavy metals (total) | total limit of 10 ppm, determined as lead, according to the BP limit tests. | |||
| Microbiological | finished products incorporating this substance must be in accordance with AGRD2 specifications** | |||
| Adenine | - | NMT 5% of (S),S-adenosylmethionine | HPLC*§ | |
| Methylthioadenosine | - | NMT 5% of (S),S-adenosylmethionine | HPLC*§ | |
| S-adenosylhomocysteine | - | NMT 2.5% of (S),S-adenosylmethionine | 1.5% | HPLC*§ |
| ** Methods must be validated and must be able to separate (S),S-adenosylmethionine from potential degradation compounds, counter ions and (R),S-adenosylmethionine isomer § e.g. Hoffmann, J.L. (1986) Biochemistry 25: 4444-4449. ‡ e.g. Revelle et al. (1995) J. AOAC Intl. 78: 353-358. 'NMT' means 'not more than' AGRD2 = Australian Guidelines for the Registration of Drugs, Volume 2, Non-prescription Drugs Registered via Compliance Branch GC = gas chromatography HPLC = high performance liquid chromatography BP = British Pharmacopoeia USP = US Pharmacopoeia 'SAMe' = 'SAM-e' = S-adenosyl-L-methionine ICH = International Conference on Harmonisation ICH topic Q3C = Quality Guidelines: Impurities: Residual solvents |
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