Study On The Preliminary Quality Standard And Stability Of Laninamivir Octanoate

Laninamivir Octanoate (trade name: Inavir), Japanese company Daiichi Sankyomade the product on sale in Japan in March2009with permission from the Australian pharmaceutical company Biota Holdings. September2010for the first time inJapan it was approved to treat influenza A and B, laterly it’s indication to preventinfluenza was approved in2013. Now clinical trials Phase II is being conducted byFDA for this product. Our group take N-acetylneuraminic acid as the starting material to synthesize laninamivir octanoate, after methylation, acetylation, azide formation, azide reduced to amine, and with N, N’-two-tert-butoxycarbonyl-pyrazole-1-guanidino to connect, forming benzhydryl, octanoyl chloride condensation, and so on, totally12steps to obtain the final compound, whose formula is C21H36N4O8, molecularweight472.53, chemical name (4S,5R,6R)-5-acetamide-4-guanidino-6-[(1R,2R)-2-hydroxy-1-methoxy-2-(octanoyl)propyl]-5,6-dihydro-4H-pyran-2-carboxylic acid. In t-his paper, in accordance with the "Chinese Pharmacopoeia"2010version and relevantdrug development guidelines, three batches of scale-up samples was taken for thelaninamivir octanoate. In Quality standard research project, the study was on the a-ppearance, solubility, melting point, identification, inspection, measurement of relatedcompounds, determination of content and other projects of laninamivir octanoate, a-nd intends to develop a Quality Standards (Draft) of laninamivir octanoate. In exa-mination of related substances, using a method of principal component of self-cont-rolwithout correction factor to get the impurities data, founded a set of chromatogr-aphic conditions to check related substances in laninamivir octanoate and carried o-ut Methodology of the study, such as specificity, linearity, precision, reproducibilityan-d stability of the solution and other items, the results showed that this methodis simple, good specificity, good reproducibility, high sensitivity; in addition, in thed-etermination of content of laninamivir octanoate there were carried out linearity and linearity range, precision, recovery rate (accuracy), solution stability, repeatability, methodological study and so on. The results showed that the method has simpleoperation, good accuracy, good repeatability, reliable results, and good linearity isensured under the25~1000μg/ml concentration range of the product, and this meth-od can be used to control laninamivir Octanoate Quality; stability in the experimen-tal study, samples of three batches were tested for the factors affecting test, including the quality changing of the in case conditions over time at different temperature,relative humidity and strong light, etc. Then the study carried out for accelerated testing and long-term stability tests. Thus, the establishment of the product’s qualitystandard (draft) provides a new choice for controlling the quality of laninamiviroctanoate; checking the relevant data of laninamivir octanoate in different temperat-ure,humidity and light stability tests, founded that the process to synthesize our productis feasible with good stability, while the experimental data provides a better reference for the production, packaging, storage and the period’s determining of validity ofthe drug.