In order to confirm which coating removal method has minimal effect on determination of the contents of cobamamide tablets. The content of washing cobamamide tablets ,which was carried out different pretreatment-process including scraping, coated sugar, uncoated tablets were determined by high performance liquid chromatography.The results showed that various coating removal methods influnced the measurement results of the content,compared with the uncoated tablets , the result by washing tablets inprocessing weight was smaller and the labeled was the most close amount was lower,the concentration of sugar coated tablets was not stable by direct method, which couldn’t representation accurately the labeled amount. Therefore, the effect of washing tablets processing on the content of cobamamide tablets were minimum.The effect of coating removaling by washing tablets in the determination of the content of cobamamide tablets was the best.