Synthesis And Stability Of Folic Acid

The objectives of this paper are to study physical and chemical properties of folic acid which relate to its quality,to establish new methods and offer datas for quality control.The content of this study includes:1. Related substances. The HPLC method was adopted to detect the related substances in folic acid,and the new method was validated by the test.2. Assay. The HPLC method was adopted to determinate the content of folic acid,and the method was validated by the experiment.3. Research of detection method for stability of folic acid.The results were obtained. 1.Related substances:(1) The best chromatographic condition was chosen.(2)The theoretical plates of peak of folic acid were 4867.The resolution between folic acid and the near related substance was more than 4.0.(3)After folic acid were treated by acid,alkali,oxidation,heat and strong light,the degradation products could be base-line separated from the main peak.(4)The lowest detection limit was 0.02 ng.(5)The RSD of the main peak areas in reproducibility test was 0.07%.The RSD of the peak of impurity A in repeatability test and in intermediate precision test was 1.77%; The RSD of the peak of impurity D in repeatability test and in intermediate precision test was 1.76%. The RSD of the peak of biggest single impurity in repeatability test was 0.77%. The RSD of peak of other total impurities in repeatability test was 1.15%.(6)Stability of the test solution:The RSD of the main peak areas was 0.06%. 2.Assay:(1)The best chromatographic separation condition was chosen.(2)The theoretical plates of main peak of folic acid were 4678.The tailing factor of main peak was 1.269.(3)The calibration curve for main peak was Y=39290020X-581.the correlation coefficient was 0.9999.(4)The lowest quantification limit of folic acid was 0.18 ng.(5)The RSD of reproducibility test and repeatability test were 0.05% and 0.10%.(6)In solution stability test,the RSD of the main peak area was 0.09%.The test solution was stable in 12 hours.(7) Their average recovery rate for the assay was 100.5%,and the RSD was 0.56%.3.The 9-month long-term stability data and accelerated stability data for three batches of folic acid show that appearance and content of folic acid were no difference and related substances of folic acid had the increasing trends. Shoud preserve folic acid in well-closed, light-resistant containers.The three methods of folic acid for indentification,related substances detction and assay were established,and the stability study of folic acid were studied.By validation,the three new methods were proved to be specific,accurate and sensitive.These newly established methods may be used in the new drug development process for quality control and stability study.