Study On The Synthesis And Quality Of Duloxetine Hydrochloride

Duloxetine Hydrochloride (1, (S)-N-methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamine hydrochloride) is a dual inhibitor of serotonin andnorepinephrine reuptake and has a better pharmacological profile for anantidepressant drug. Serotonin and norepinephrine neurotransmitters areintimately involved in a number of physiological and behavioral processes,suggesting that duloxetine (ability to produce a robust increase ofextracellular serotonin and norepinephrine levels) is not only a highlyefficient antidepressant agent for treating psychiatric disorders, but also canbe used for treating other symptoms such as urinary incontinence, diabeticperipheral neuropathic pain and fibromyalgia. Duloxetine has some featuressuch as improved efficacy, tolerability, safety, faster recovery,fewer sideeffects than other antidepressant in the clinical investigations.On the basis of the investigation about the synthetic methods ofduloxetine which is a promising chiral medicine, an economical andreasonable synthetic route was studied. The target compound was obtainedthrough resolution by S-(+)-mandelic acid and five steps. The startingmaterials include 2-acetylthiophene, paraformaldehyde and concentratedand low cost process for the synthesis of duloxetine hydrochloride isattained.They conduct the structure corroboration about the material made bythe above processing and make comparison with the references. Elementalanalyses data accord to the molecular structure. IR of the samle isconsistent with reference. UV spectrum of sample is consistent with thereference. NMR spectrum is detected, and obtained the data of carbonhydrogen bonds. They determined every carbon atom and hydrogen itemsby 1H-1H COSY,HMQC,HMBC. The obtained data accord to themolecular structure, and the dataof reference is totally in accordance withthat of sample.The structures were also determined based on FAB-MSspectral analyses. Duloxetine,s crystal structure was determined by an X-ray crystallographic analysis.In the article, Duloxetine,s quality standard is basically determinedafter careful research on the identification, relative material limit, organicvolatile impurities and effective ingredient contents. The stability researchhas also been performed under high temperature circumstances, high wetcircumstances and highlight circumstances respectively. Conclusions havebeen drawn out that at cool circumstances, the quality is stable, soduloxetine preserve in well-closed containers, protected from light. Store atroom temperature.