Qualitative Study And Separation Of Its Related Substances Of New Drug 9010-Ⅰ

As a constituent of two redox coenzymes , namely flavin mononucleotide(FMN) and flavin adenine dinucleotide(FAD), riboflavin, take part in complex oxidation-reduction process and have very important pharmacological effects.Riboflavin deficiency will bring about all kinds of pathological effets. Besides traditional riboflavin deficiency diseases, some research in recent year suggest riboflavin have close relation to cancer, heart disease, hypertension, thermal injury, antiarthritic and so on. However, as a water-souble vitamins, it is easy for riboflavin to excrete out from body in urine and sweat, so riboflavin bioavalability is very low and it is very difficult for riboflavin to exhibit therapuitic effects and easily causes all kind of diseases as the result of riboflavin deficiency. Academy of Military Medical Science had succeed in developing the oil suspension injection of the long effective riboflavin in the 1960s, The previous research suggested the long effective riboflavin was a mixture of different chemical region isomers of riboflavin and the9010- I was a mainly principle of he mixture, the riboflavin derivative was firstly synthesized by us. Synthtic technology of 9010- I being mature, study quality of this new drug and separation of its related substances were carried out.The study of this new drug focus the purity, content, stability tests, establish the analytical methods for quantitative control in order to ensure quality of the new drug product. This paper has studied the quality and stability of 9010- I , The works have been used as part of the documents in applying for approval of clinical trial.Following sections are included:1. Study on the separation of the impurities in 9010— 1 , establish the High Perform Liquid Chromatograph(HPLC) method for determination of 9010— I content and its related substances. The conditions of HPLC: Instrument was Waters 2695-2996 with PDA detection at 269nm, Empower data system with meu32 soft ware; After comparison test. Agilent, Zorbax SB-C₁8 column(250x4.6mm, 5μ) was used with moving phase (acetonitrile-water-H₃PO₄/KH₂PO₄ buffer salt =48%/20min⁶0%/25min, pH2. 5); pressure: 1. 3X 107^l. 8X 107 Pa; flow rate: 1.6mL/min; injection amount: 20ul; The quantitative method was external standerd (ESTD).2.The related substances of 9010- I are identified by GOMS . One of them has been synthesis as the reference standard and confirmed by GC-MS.3. Study on the solubility, hydroscopicity, solvent residual, loss on drying, etc by different analysis methods, provide theory basis for establishing of the drug specification. Stability of heat, humility and light have been determined for package, storage and transfer. Stability of storage at room temperature is tested for the expire date. The results show that 90] 0— I has good stability on heat and humility, but it is unstable under the situation of light. It should be store in dark and dry.The works have been used as part of the documents in applying for approval of clinical trial.