Description
Captopril disulfide is a metabolite and symmetrical disulfide form of the angiotensin converting enzyme (ACE) inhibitor captopril . Captopril disulfide is the main degradation product of captopril and is formed by oxidation. It is a potential impurity in commercial preparations of captopril. Captopril disulfide inhibits angiotensin I-induced increases in mean arterial pressure in anesthetized dogs (ID
50 = 0.231 mg/kg, i.v.).
Chemical Properties
White Solid
Uses
Captopril Disulfide (Captopril EP Impurity A) is a metabolite of Captopril. A new antihypertensive agent.
Definition
ChEBI: An organic disulfide in which the disulfide bond links two units of captopril. It is a secondary metabolite of captopril.
Synthesis
50 g of free acid, 200 g of water and 66 g of ammonia were added to a 1000 ml three-necked flask. The reaction was held at a controlled temperature of 35C for 2 hours. At the end of the reaction, control at this temperature dropwise addition of hydrochloric acid 102g until the pH to 0.5, stirring for 30 minutes to re-test the pH. add 3g of zinc powder, heating to 38 , holding reaction for 2h. After the completion of the reaction was lowered to room temperature was extracted with 300g of dichloromethane in three times. The organic phases were combined and the dichloromethane was distilled under normal reduced pressure. After evaporation and drying with 80g ethyl acetate recrystallization, warming to 70 dissolved clear, slow cooling to 5 crystallization. Filtering, drying under reduced pressure. Got Captopril 33g. .
It was tested to meet the standards of the 2015 edition of the Chinese Pharmacopoeia. Among them, the melting point of the product was 105-108C (Pharmacopoeia standard 104-110C), the specific rotation was -126-130 (Pharmacopoeia standard -126-132), and the disulfide was 0.2% (Pharmacopoeia standard less than 1%). The purity is above 99.6%.
References
[1] T KOMAI. In vitro studies on the metabolic pathway of SQ 14225 (Captopril) and mechanism of mixed disulfide formation.[J]. Journal of pharmacobio-dynamics, 1981, 4 9: 677-684. DOI:
10.1248/bpb1978.4.677[2] BENEDETTA PASQUINI . Cyclodextrin- and solvent-modified micellar electrokinetic chromatography for the determination of captopril, hydrochlorothiazide and their impurities: A Quality by Design approach[J]. Talanta, 2016, 160: Pages 332-339. DOI:
10.1016/j.talanta.2016.07.038[3] N O’HARA K H H Ono. Potentiation of bradykinin-induced decrease of blood pressure in dogs by SO 14,551, the disulfide metabolite of captopril.[J]. Japanese journal of pharmacology, 1982, 32 5: 934-937. DOI:
10.1254/jjp.32.934
