目的 評價國內目前市售的硫酸氨基葡萄糖固體口服制劑的質量，考察現(xiàn)行標準中存在的問題，為生產和質量控制提供參考。方法 對硫酸氨基葡萄糖固體口服制劑進行國家藥品抽檢（共73批，涉及8家生產企業(yè)），采用現(xiàn)行各企業(yè)執(zhí)行的注冊標準（共9個標準）對抽檢樣品進行法定檢驗。同時對產品進行探索性研究，表觀溶解度參照《美國藥典》（USP）1236通則；含量測定方法參照USP43硫酸氨基葡萄糖氯化鈉項下相關方法；有關物質方法參照原研企業(yè)標準；囊殼鉻含量測定方法按照《中國藥典》2020年版明膠空心膠囊項下相關方法；建立近紅外光譜一致性檢驗模型。結果 73批次硫酸氨基葡萄糖制劑合格率97.3%，2批樣品有關物質檢查項目不合格。各家質量標準存在一定差異，個別企業(yè)質量標準不完善，有待提高，質量標準中部分重要項目檢測方法待改進。此外，個別企業(yè)應考慮制劑配方工藝的合理性、包裝材料的密封性和防潮措施等。探索性研究結果顯示，目前各企業(yè)執(zhí)行標準中均沒有原料藥溶解性檢驗，建議企業(yè)關注晶型等可能影響溶解度的因素；法定檢驗采用C₈色譜柱的結果較探索性結果整體偏高，采用氯離子作為主成分峰進行含量控制方法不專屬，紫外可見分光光度法操作復雜、結果偏差較大，建議改為更為簡便和專屬的HPLC法；原料藥為非復鹽的受試批次制劑的雜質檢出種類、已知雜質果糖嗪和脫氧果糖嗪含量、其他已知雜質類別和總雜含量高于其他受試企業(yè)樣品，推斷原因為其易吸濕；泡騰片中果糖嗪含量較高，未知雜質數(shù)量多于其他劑型，推測原因為輔料較多；與膠囊劑相比，片劑含有的雜質更多，提示片劑生產過程中制粒、整粒等溫度較高的步驟會對產品質量產生一定影響；可按生產廠家建立近紅外光譜一致性模型或相關系數(shù)模型，補充本品的快速篩查方法。結論 各企業(yè)質量標準尚存在一定差異，個別企業(yè)質量標準不完善，有待提高，質量標準中部分重要項目的檢測方法有待改進。應建立統(tǒng)一的國家標準，建立專屬性強、準確度高的檢測方法。

Objective To evaluate the quality of glucosamine sulfate solid oral preparations in China, and investigate the existing problems in the current standards, so as to provide reference for its production and quality control. Method The medicine post market quality surveillance of glucosamine sulfate solid oral preparations was conducted (73 batches in total, involving eight production enterprises). Use the current registration standards implemented by various enterprises (a total of nine standards) to conduct statutory inspections on sampled samples. At the same time, exploratory research was conducted on the product, with the apparent solubility referring to general rule 1236 of the United States Pharmacopoeia (USP). The content determination method shall refer to the relevant methods under USP43 glucosamine sulfate sodium chloride. Related substance methods refered to the standards of the original research enterprise for relevant material methods. The determination method for chromium content in the capsule shell shall be in accordance with the relevant methods under the gelatin hollow capsules section of the 2020 edition of the Chinese Pharmacopoeia. Establish a consistency testing model for near-infrared spectroscopy. Result The qualification rate of 73 batches of sulfated glucosamine preparations was 97.3%, and the relevant substance inspection items of two batches of samples are unqualified. There are certain differences in quality standards among different companies, and some companies have incomplete quality standards that need to be improved. The testing methods for some important items in the quality standards need to be improved. In addition, individual enterprises should consider the rationality of the formulation process, the sealing of packaging materials, and moisture-proof measures. The exploratory research results show that there was currently no testing for the solubility of raw materials in the execution standards of various enterprises. It is recommended that enterprises pay attention to factors such as crystal form that may affect solubility. The results of using C₈ chromatographic column for statutory testing were generally higher than exploratory results. The method of using chloride ions as the main component peak for content control was not exclusive, and the operation of UV visible spectrophotometry was complex with significant deviation in results. It is recommended to change to a more convenient and exclusive HPLC method. The impurity detection types, levels of known impurity fructose and deoxyfructozine, other known impurity categories, and total impurity content of the test batch preparation with non double salt raw materials are higher than those of other test enterprise samples. It is inferred that the reason is that it is easy to absorb moisture. The content of fructosezine in effervescent tablets is relatively high, and the number of unknown impurities is higher than that of other dosage forms. It is speculated that the reason is due to a large number of excipients. Compared to capsule formulations, tablets contain more impurities, indicating that higher temperature steps such as granulation and granulation during the tablet production process can have a certain impact on product quality. A near-infrared spectral consistency model or correlation coefficient model can be established according to the manufacturer to supplement the rapid screening method for this product. Conclusion There were still some differences in the quality standards of various enterprises. The quality standards of individual enterprises and the detection methods of some important items in the quality standards need to be improved. A unified national standard, including specific and accurate detection methods, should be established.

R926

青島海洋科學與技術試點國家實驗室海洋藥物與生物制品功能實驗室開放性課題（LMDBKF201806）；中國食品藥品檢定研究院學科帶頭人培養(yǎng)基金（2021X6）；化學藥品質量研究與評價重點實驗室學科建設課題（2023HYZX04）