Methionine

1. Nonproprietary Names

BP: Methionine JP: L-Methionine PhEur: Methionine USP: Methionine

2. Synonyms

a-Amino-g-methylmercaptobutyric acid; (S)-2-amino-4- (methylthio)butanoic acid; 2-amino-4-(methylthio)butyric acid; Lmethionine; methioninum; g-methylthio-a-aminobutyric acid.

3. Chemical Name & CAS Registry

(2S)-2-Amino-4-methylsulfanylbutanoic acid [63-68-3]

4. Empirical Formula & Molecular Weight

C5H11NO2S 149.21

5. Structural Formula

6. Applications

Methionine is used in oral pharmaceutical formulations as a flavoring agent.(1) It has been included in parenteral formulations as a pH controlling agent,(2) and it has also been used experimentally as an antioxidant with antibodies.(3) Methionine is also used therapeutically in oral tablets

7. Description

Methionine occurs as a white or almost white, crystalline powder or colorless crystals.

8. Pharmacopeial Specifications

See Table I.

9. Typical Properties

Acidity/alkalinity pH = 5.6–6.1 (1% w/v aqueous solution)(1) Density 1.34 g/cm3(1) Melting point 280–2828C(4) Solubility Soluble in water, dilute acids, and alkalis. Insoluble in absolute ethanol, ethanol (95%), benzene, acetone, and ether.

10. Stability & Storage

Methionine is sensitive to light and should be stored in a cool, dark place.

11. Incompatibilities

Methionine is incompatible with strong oxidizing agents.

12. Method of Manufacture

Numerous methods have been described for manufacture of methionine, including hydrolysis of methionine amide(5)and 5-(bmethylmercaptoethyl)-hydantoin.(6)

13. Safety

Methionine is used in oral pharmaceutical formulations. The pure form of methionine is mildly toxic by ingestion and by the IP route. LD50 (rat, IP): 4.328 g/kg(7) LD50 (rat, oral): 36 g/kg

14. Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of the material handled.

15. Regulatory Status

Included in the FDA Inactive Ingredients Database (oral tablets). Included in parenteral preparations (injection solutions; powders for reconstitution) licensed in the UK.

16. Related Substances

D-Methionine; DL-methionine. D-Methionine CAS number [348-67-4] Comments The EINECS number for D-methionine is 206-483-6. DL-Methionine CAS number [59-51-8] Acidity/alkalinity pH = 5.6–6.1 (1% w/v aqueous solution) Density 1.34 g/cm3 Dissociation constant pKa1 = 2.28 at 258C; pKa2 = 9.21 at 258C Melting point 2818C Solubility Soluble in dilute acids and alkalis. See also Table II. Comments The EINECS number for DL-methionine is 200-432-1.

17. Comments

Methionine is used in paracetamol poisoning to prevent hepatotoxicity, and is frequently included in paracetamol formulations for this purpose.(8,9) L-Methionine is an essential amino acid and is included in amino acid solutions for parenteral nutrition.(8) It has been used to treat liver disorders and also to lower urinary pH.(8) A specification for L-methionine is contained in the Food Chemicals Codex (FCC).(10) The EINECS number for L-methionine is 200-562-9. The PubChem Compound ID (CID) for L-methionine is 6137