目的 通過測定不同來源的硫辛酸注射液中的頂空殘氧量和溶解氧量以及有關(guān)物質(zhì)和主成分的含量，分析數(shù)據(jù)變化趨勢，為硫辛酸注射液的質(zhì)量控制提供技術(shù)參考。方法 以原研制劑、自研3批不同溶氧量與殘氧量的樣品以及市售不同廠家樣品為試驗對象，采用高效液相色譜法測定不同樣品的有關(guān)物質(zhì)[雜質(zhì)A（6，8-上硫辛烷酸）、雜質(zhì)B（氧化雜質(zhì)）、雜質(zhì)C（降解雜質(zhì)）]、含量和聚合物，X-325i頂空殘氧/溶氧分析儀測定溶氧量與殘氧量，進行高溫、光照、低溫、凍融循環(huán)等影響因素試驗，以及加速試驗、長期試驗考察穩(wěn)定性。結(jié)果 較高溶氧殘氧產(chǎn)品在高溫條件下雜質(zhì)B、C和雜質(zhì)總量增長趨勢明顯；光照無外包裝條件下，樣品中溶氧量與殘氧量均顯著降低，雜質(zhì)A和聚合物增長顯著；光照帶外包裝條件下各樣品均穩(wěn)定；低溫條件下各樣品均穩(wěn)定；凍融條件下低溶氧量樣品不受影響，高溶氧量樣品聚合物增加明顯；加速條件下，所有自研制劑樣品中雜質(zhì)B和C增加趨勢明顯，所有樣品中溶氧量呈下降趨勢，殘氧量基本無變化；長期條件下，高溶氧殘氧樣品雜質(zhì)C和聚合物有增長趨勢。結(jié)論 越低的氧含量越有利于質(zhì)量控制，建議在中間產(chǎn)品中控制溶解氧<2 μg/mL，殘氧量<2.0%，產(chǎn)品較穩(wěn)定。

Objective To investigate the effects of different dissolved oxygen and residual oxygen on the quality of Thioctic Acid Injection, and to provide technical reference for Thioctic Acid Injection in order to improve the quality. Methods The original preparation, three batches of self-prepared samples with different dissolved oxygen content and residual oxygen content and samples from different manufacturers in the market were used as the test objects. HPLC methods was applied to measure impurities including impurity A (6,8-sulfooctanoic acid), impurity B (oxidation impurity), impurity C (degradation impurity), content and polymer. The dissolved oxygen and residual oxygen were measured by X-325i headspace residual oxygen/dissolved oxygen analyzer. The influence factors test of high temperature, light, low temperature, freeze-thaw cycle, accelerated test and long-term test were carried out to investigate the stability. Results Content of impurities B, C and total amount of impurities increased obviously under high temperature conditions. The dissolved oxygen and residual oxygen in the samples were significantly reduced under the condition of light without outer packaging, and the impurities A and polymer increased significantly. All samples were stable under the light band packaging conditions. All samples were stable under low temperature conditions. The samples with low dissolved oxygen content were not affected under freeze-thaw conditions, but the polymer in the sample with high dissolved oxygen content increases significantly. Under accelerated conditions, impurities B and C in all self-developed preparation samples increased significantly, dissolved oxygen content decreased, and residual oxygen basically remained unchanged in all sample; under long-term conditions, impurity C and polymer in high dissolved oxygen and residual oxygen samples had an increasing trend. Conclusion The lower the oxygen, the better the quality. It is recommended that dissolved oxygen is below 2 μg/mL and residual oxygen is below 2.0%, which the product is stable.

R927.1