Studies On Compounds Monitoring Method On Synthesis Process Of Vinorelbine

Vinorelbine is a novel semisynthesis vinca alkaloid. It is usually obtained from vinblastine by chemosynthesis. Since pharmaceutical products have high product profit, patents of technique production including determination methods are well protected. Researches on detecting of source material, intermediates and the end products simultaneity are seldom reported as well as quality control of the production process. This project, which as a part of"industrial production of vinorelbine", studies on the determination methods on objects that involve in the chemosynthesis process and the stability of the main product. It helps give the necessary scientific basis for setting down the determination and control standards of synthesizing, separation and conservation of vinorelbine as GMP requires.Based on the demanding of high efficiency and convenient of the determination method for industrial producing. This paper discusses the combined determination method of TLC and HPLC in tracing the chemosynthesis process.TLC experiments showed that when choose petroleum ether : chloroform : acetone : diethyl amine (23.5:12:2:2.5; V/V/V/V) as developer, Rf of source material, intermediates and the end products can be controlled between 0.3～0.5, objects can be well separated on silica gel. The Rf of vinblastine sulfate, anhydrovinblastine and vinorelbine was 0.4200, 0.3652, 0.3125 respectively. It can be regarded as a main detecting method for quickly tracing the chemosynthesis process.HPLC method, which using C18 as stationary phase, Methyl alcohol : acetonitrile : diethyl amine : high purity water = 420:252:3:225 (V/V/V/V), adjusted with orthophosphoric acid to pH 6.5 as mobile phase is used to give quantitative analysis to vinorelbine. The eluent was pumped through the column at a flow-rate of 1 ml/min, the volume injected was 10μl and the eluate was monitored at 267 nm. Accuracy was expressed as the recovery and found that it can arrive at 100.4%. vinblastine sulfate, anhydrovinblastine and vinorelbine can be separated totally at the base line in 35 minutes. The relative retention time for each component was: 0.3556, 1 and 0.7595, respectively. When using this condition to detect vinorelbine, results indicated that the peak area of vinorelbine over the internal standard varied linearly with concentration over the range used. The LOD is 0.1608μg/ml.The stability of vinorelbine and factors of influencing the stability were studied. Results showed that vinorelbine was stable below 40℃and under the neutrality condition, but sensitive to strong light and high temperature. Under the daylight lamp, it began to decompose after 4 days; when temperature is above 60℃, it began to decompose after 90 min. Oxidant and deoxidiser that of low concentration have few effects on its stability. Results indicated that separation and conservation of vinorelbine should be better done under the condition of darkness and below temperature 40℃.The applying of combined determination method of TLC and HPLC can analyze all objects that involved in the chemosynthesis process simultaneity. Meanwhile, technical parameter of quality control for synthesizing, separation and preservation of vinorelbine were found out by studying the stability of it. It gives credible references to industrial producing of vinorelbine and technical references of quality control to other natural products.