Study On Synthesis And Preparation Of Levetiracetam

The chemical formula of levetiracetam is (S)-α-Ehtyl-2-oxo-l-pyrrolidiny lacetamide, which is the only wide spectrum antiepileptic drug reported, as a second class of acetylcholine agonists and a kind of pyrrolidone derivatives.Featuring special mechanism of action and significant pharmacokinetic characteristics, levetiracetam gradually received the acceptance of the doctor and patient with high therapeutic index, security, fewer adverse reactions, etc. Levetiracetam is not only can be used as monotherapy epilepsy, but also used for children with epilepsy and generalized epilepsy. Levetiracetam showed a wide range of applications in epilepsy treatment, however, due to the original drug Keppra with higher prices, the usage of levetiracetam has been limited. In this paper, the synthesis of levetiracetam and related preparations were studied and the structure characterization, content quality research work in accordance with the standard were also demonstrated, so that more patients can benefit with the lower costs.On the basis of the research and analysis of literature, we synthesized levetiracetam from (S)-2-aminobutanamide tartrate as raw materials, getting (S)-2-aminobutanamide by dripping potassium hydroxide in isopropyl alcohol solution, then reacted with hydrogen chloride in isopropyl alcohol solution, finally obtained crude levetiracetam by acylation with 4-chlorobutyryl chloride and cyclization, purification with acetic acid acetate/acetone mixed solvent, eventually the total yield was 58.5%-67.2%. Demonstrating the result structure weither compliance with levetiracetam by UV, IR,MS, FT-IR,1H-NMR. The synthesis mild reaction conditions, easy operation, low cost, more suitable for industrial production. The synthesis routes has the superiorities with relatively mild reaction conditions, pharmaceutical raw materials readily available, easy to operate, reduce production costs, as well as more suitable for industrial production.Since no legal quality standards and analysis methods of levetiracetam can be provided in pharmacopoeias of every countries. In this study, according to the Chinese Pharmacopoeia 2010 Edition, which involved the comprehensive analysis methods and quality research on it by modern analysis technology. Including the aspects of character, specific rotation, identification, impurity inspection, determination, etc., we establish the HPLC method of levetiracetam, right levetiracetam and related substances. Quality standard draft is formulated based on the study results aboved.Levetiracetam tablet and injection were developed, and establish methods for their quality control were studied. The prescriptions were preliminary filtered according to UCB’s patents, references and 2010 China Pharmacopoeia, and the formulations prepared in line with regulations.