目的 評(píng)價(jià)國(guó)內(nèi)目前市售的硫酸氨基葡萄糖固體口服制劑的質(zhì)量，考察現(xiàn)行標(biāo)準(zhǔn)中存在的問題，為生產(chǎn)和質(zhì)量控制提供參考。方法 對(duì)硫酸氨基葡萄糖固體口服制劑進(jìn)行國(guó)家藥品抽檢（共73批，涉及8家生產(chǎn)企業(yè)），采用現(xiàn)行各企業(yè)執(zhí)行的注冊(cè)標(biāo)準(zhǔn)（共9個(gè)標(biāo)準(zhǔn)）對(duì)抽檢樣品進(jìn)行法定檢驗(yàn)。同時(shí)對(duì)產(chǎn)品進(jìn)行探索性研究，表觀溶解度參照《美國(guó)藥典》（USP）1236通則；含量測(cè)定方法參照USP43硫酸氨基葡萄糖氯化鈉項(xiàng)下相關(guān)方法；有關(guān)物質(zhì)方法參照原研企業(yè)標(biāo)準(zhǔn)；囊殼鉻含量測(cè)定方法按照《中國(guó)藥典》2020年版明膠空心膠囊項(xiàng)下相關(guān)方法；建立近紅外光譜一致性檢驗(yàn)?zāi)Ｐ汀?b>結(jié)果 73批次硫酸氨基葡萄糖制劑合格率97.3%，2批樣品有關(guān)物質(zhì)檢查項(xiàng)目不合格。各家質(zhì)量標(biāo)準(zhǔn)存在一定差異，個(gè)別企業(yè)質(zhì)量標(biāo)準(zhǔn)不完善，有待提高，質(zhì)量標(biāo)準(zhǔn)中部分重要項(xiàng)目檢測(cè)方法待改進(jìn)。此外，個(gè)別企業(yè)應(yīng)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(jié)果顯示，目前各企業(yè)執(zhí)行標(biāo)準(zhǔn)中均沒有原料藥溶解性檢驗(yàn)，建議企業(yè)關(guān)注晶型等可能影響溶解度的因素；法定檢驗(yàn)采用C₈色譜柱的結(jié)果較探索性結(jié)果整體偏高，采用氯離子作為主成分峰進(jìn)行含量控制方法不專屬，紫外可見分光光度法操作復(fù)雜、結(jié)果偏差較大，建議改為更為簡(jiǎn)便和專屬的HPLC法；原料藥為非復(fù)鹽的受試批次制劑的雜質(zhì)檢出種類、已知雜質(zhì)果糖嗪和脫氧果糖嗪含量、其他已知雜質(zhì)類別和總雜含量高于其他受試企業(yè)樣品，推斷原因?yàn)槠湟孜鼭?；泡騰片中果糖嗪含量較高，未知雜質(zhì)數(shù)量多于其他劑型，推測(cè)原因?yàn)檩o料較多；與膠囊劑相比，片劑含有的雜質(zhì)更多，提示片劑生產(chǎn)過程中制粒、整粒等溫度較高的步驟會(huì)對(duì)產(chǎn)品質(zhì)量產(chǎn)生一定影響；可按生產(chǎn)廠家建立近紅外光譜一致性模型或相關(guān)系數(shù)模型，補(bǔ)充本品的快速篩查方法。結(jié)論 各企業(yè)質(zhì)量標(biāo)準(zhǔn)尚存在一定差異，個(gè)別企業(yè)質(zhì)量標(biāo)準(zhǔn)不完善，有待提高，質(zhì)量標(biāo)準(zhǔn)中部分重要項(xiàng)目的檢測(cè)方法有待改進(jìn)。應(yīng)建立統(tǒng)一的國(guó)家標(biāo)準(zhǔn)，建立專屬性強(qiáng)、準(zhǔn)確度高的檢測(cè)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(xué)與技術(shù)試點(diǎn)國(guó)家實(shí)驗(yàn)室海洋藥物與生物制品功能實(shí)驗(yàn)室開放性課題（LMDBKF201806）；中國(guó)食品藥品檢定研究院學(xué)科帶頭人培養(yǎng)基金（2021X6）；化學(xué)藥品質(zhì)量研究與評(píng)價(jià)重點(diǎn)實(shí)驗(yàn)室學(xué)科建設(shè)課題（2023HYZX04）