注射用頭孢噻肟鈉的質(zhì)量評價

王韻?王強?李香荷?高燕霞

摘要：目的 按照國家藥品抽檢要求，評價國內(nèi)不同企業(yè)生產(chǎn)的注射用頭孢噻肟鈉的質(zhì)量。方法 國家標準檢驗與探索性研究相結(jié)合，對全國范圍內(nèi)的224批次抽檢樣品進行評價。結(jié)果 按法定標準檢驗，合格率為100%，但產(chǎn)品在溶液的澄清度、溶液的顏色、裝量差異等項目存在邊緣合格產(chǎn)品；探索性研究結(jié)果顯示，法定標準在雜質(zhì)控制、聚合物測定等方面存在一定不足，原料缺少對生產(chǎn)過程產(chǎn)生的基因毒性雜質(zhì)2-巰基苯并噻唑的控制。結(jié)論 國產(chǎn)注射用頭孢噻肟鈉質(zhì)量較優(yōu)，且近年有明顯質(zhì)量提升。建議修訂質(zhì)量標準，完善聚合物、有關(guān)物質(zhì)等控制，建議生產(chǎn)企業(yè)關(guān)注產(chǎn)品中2-巰基苯并噻唑的潛在安全風險。

關(guān)鍵詞：注射用頭孢噻肟鈉；質(zhì)量評價；有關(guān)物質(zhì)；聚合物；基因毒性雜質(zhì)

中圖分類號：R978.1文獻標志碼：A

Abstract Objective To evaluate the quality of cefotaxime sodium for injection produced by different domestic enterprises according to the national drug sampling requirements. Methods According to the results of national standard inspection combining research， 224 batches of sampled samples from the nationwide were evaluated. Results The qualified rate was 100%， but there were some edge qualified products on the items of solution clarity， solution color， and weight variation. The exploratory research results showed that the legal standard was insufficient on impurity profile control and polymer determination， and lacks the control of genotoxic impurity 2-mercaptobenzothiazole in raw material which was produced in the manufacture process. Conclusion The quality of domestic cefotaxime sodium for injection is good and significantly improved in recent years. It is suggested to revise the quality specification including to improve the determination methods on polymer and related substances， and is suggested that the manufacturers pay attention to the potential safety risks of 2-mercaptobenzothiazole in the products.

Key words Cefotaxime sodium for injection; Quality evaluation; Related substances; Polymers; Genotoxic impurity

頭孢噻肟鈉（cefotaxime sodium）為第三代頭孢菌素，于1975年由法國Roussel Uclaf公司研究所發(fā)現(xiàn)，并與德國Hoechst公司共同開發(fā)，1980年在德國上市[1]。具有抗菌譜廣、穩(wěn)定、使用安全的特性，臨床上主要用于敏感細菌引起的急性和慢性細菌感染[2]。

頭孢噻肟鈉制劑國外有注射用頭孢噻肟鈉和頭孢噻肟鈉注射液兩種，我國目前僅批準有注射用粉針劑。根據(jù)對制劑企業(yè)的調(diào)研，國內(nèi)注射用頭孢噻肟鈉均由無菌原料直接分裝制成，生產(chǎn)過程中未添加其他輔料。經(jīng)查詢國家藥品監(jiān)督管理局網(wǎng)站，國內(nèi)現(xiàn)有注射劑生產(chǎn)企業(yè)76家，批準文號227個，有0.25、0.5、0.75、1.0、1.5、2.0、2.5、3.0和4.0 g共9種規(guī)格。注射用頭孢噻肟鈉收載于《中國藥典》2020年版[3]及USP44版[4]?！?br>