Methionine

• BPMethionine
• JPL-Methionine
• Ph. Eur.Methionine
• USP–NFMethionine

L-Methionine; (S)-2-amino-4-(methylthio)butanoic acid; methioninum; DL-methionine (racemate, separate monograph)

(S)-2-Amino-4-(methylsulfanyl)butanoic acid · [63-68-3]

UNII AE28F7PNPL · PubChem CID 6137

C5H11NO2S · 149.21

Antioxidant, chelating agent

Typical concentrations: — · Dosage forms: Sterile (parenteral/ophthalmic)

Used as an antioxidant in parenteral protein and peptide formulations, where free methionine is preferentially oxidised and protects methionine residues of the protein (typically in the low millimolar range, for example about 1–10 mM). It is also used as a nutritional amino acid in parenteral and enteral nutrition, and therapeutically as an antidote for paracetamol overdose.

White crystalline powder or colourless crystals with a slight characteristic odour. It is an essential sulfur-containing amino acid.

Melting point

decomposes at about 280 °C

Solubility

soluble in water; very slightly soluble in ethanol (95%); dissolves in dilute acids and dilute alkali hydroxide solutions

pKa

≈ 2.3 (carboxyl); ≈ 9.2 (amino)

pH

about 5.5–6.5 (aqueous solution)

Stable in the solid state. In solution the thioether is readily oxidised to methionine sulfoxide (and further to the sulfone), especially in the presence of peroxides, light and metal ions. Store in a well-closed container, protected from light.

Incompatible with oxidising agents. Like other amino acids it can undergo Maillard reactions with reducing sugars.

L-Methionine is produced by fermentation or by enzymatic resolution of chemically synthesised DL-methionine.

A normal dietary component and regarded as non-toxic at excipient levels. Very high intakes can raise plasma homocysteine and have caused adverse effects in patients with liver disease.

Observe normal precautions for the quantity handled. Avoid generating dust; eye protection, gloves and a dust mask are recommended.

Permitted in the USA as a nutrient food additive (21 CFR 172.320). Included in the FDA Inactive Ingredient Database (injections) and used in parenteral biological products licensed in Europe.

DL-Methionine; cysteine; acetylcysteine; monothioglycerol; sodium metabisulfite.

Methionine is particularly useful against peroxides from polysorbates in protein formulations. Its antioxidant capacity is consumed sacrificially, so the level should be justified by forced-oxidation studies; it does not protect against all oxidation pathways (for example tryptophan oxidation is only partly reduced).