| 第 52 卷第 5 期 |  | Vol. 52 No. 5 | | 2022 年 10 月 | Oct 2022 |
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所屬欄目：分析與測試
注射用頭孢唑林鈉中一種頭孢唑林聚合物分析 |
| 于曉娜，表亞囡，劉 瑩，時(shí)佳靜，谷藝凡，任毅然，李 敏，楊夢(mèng)德，張 民*
（華北制藥河北華民藥業(yè)有限責任公司 抗生素酶催化與結晶技術(shù)國家地方聯(lián)合工程實(shí)驗室 河北省頭孢類(lèi)藥物制備技術(shù)創(chuàng )新中心，河北 石家莊 052165） |
| 摘 要：頭孢類(lèi)抗生素聚合物多為總聚物的控制，為更好進(jìn)行聚合物單個(gè)控制，建立RPHPLC法并采用柱切換-LC/MSn對聚合物雜質(zhì)進(jìn)行定性研究。結果顯示該方法可有效檢出聚合物A且專(zhuān)屬性良好，對聚合物A進(jìn)行結構確證并推測其產(chǎn)生機理，同時(shí)對該方法進(jìn)行全面的方法學(xué)驗證。各個(gè)破壞條件下聚合物A與相鄰雜質(zhì)分離度大于1.5；檢測限及定量限濃度相當于供試品濃度的0.01%及0.02%；聚合物A在定量限至4倍限度濃度范圍內與峰面積的線(xiàn)性關(guān)系良好，相關(guān)系數大于0.99；樣品中聚合物A的加標回收率在93.44%~100.96%范圍內；重復性、中間精密度中聚合物A的含量極差均為0.00%；聚合物A在常溫下穩定性較差，在冷藏條件下24 h內較穩定；在波長(cháng)變化±5 nm、柱溫變化±5 ℃，流速變化±0.1 mL/min、pH在6.7~6.8范圍內及不同色譜柱條件下，聚合物A專(zhuān)屬性良好，含量與正常條件比較無(wú)明顯差異。該方法專(zhuān)屬性良好，準確度及重復性較高，可以用于檢測注射用頭孢唑林鈉中的單個(gè)的頭孢唑林聚合物。 |
| 關(guān)鍵詞：高效凝膠色譜法；頭孢唑林鈉；聚合物雜質(zhì)；結構確證；方法學(xué)驗證 |
| 中圖分類(lèi)號：R927.1 文獻標識碼：A 文章編號：1009-9212（2022）05-0091-06 |
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| Analysis of Polymeric Impurity in Cefazolin Sodium for Injection |
| YU Xiao-na, BIAO Ya-nan, LIU Ying, SHI Jia-jing, GU Yi-fan, REN YI-ran, LI Min, YANG Meng-de, ZHANG Min*
(Huabei Pharmaceutical Hebei Huamin Pharmaceutical Co., Ltd., National and local Joint Engneering Laboratory of Antibiotic Enzyme Catalysis and Crystallization Technology, Hebei Province Cephalosporide Medicine Preparation Technology Innovation Center, Shijiazhuang 052165, China) |
| Abstract：Cephalosporin antibiotics are mostly controlled by total polymers. In order to better control the single polymer. The method of RPHPLC was established column switching-LC/MSn was used to qualitatively polymeric impurities. The results showed that this method could effectively detect polymer A with good specificity. The structure of polymer A was confirmed and the mechanism of its generation was speculated. Meanwhile, the method was comprehensively validated. The separation degree of polymer A and its adjacent impurities was greater than 1.5 under each failure condition. Limit of detection and limit of quantitation concentration were equivalent to 0.01% and 0.02% of the concentration of the tested substance; The linear relationship between polymer A and peak area was good in the concentration range from the limit of quantification to the limit of four times, and the correlation coefficient was greater than 0.99. The recoveries of polymer A ranged from 93.44% to 100.96%. The content range of polymer A in repeatability and intermediate precision was 0.00%. The stability of polymer A was poor at room temperature, but stable within 24 h under cold storage. Under the following conditions: wavelength change was ±5 nm; column temperature change was ±5 ℃; flow rate change was ±0.1 mL/min; pH value in the range of 6.7~6.8 and different chromatographic column conditions, polymer A had good specificity and no significant difference in content compared with normal conditions. This method had good specificity, accuracy and repeatability, and could be used for the determination of single polymer in cefazolin sodium for injection. |
| Key words：high performance gel chromatography; cefazolin sodium; polymeric impurities; structure confirmation; method validation |
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作者簡(jiǎn)介：于曉娜（1987—），女，河北石家莊人，工程師，研究方向：藥品質(zhì)量研究（E-mail：yuxiaona1427@126.com）。
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聯(lián) 系 人：張 民，高級工程師，研究方向：藥品工程研究（E-mail：3199365250@qq.com）。
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收稿日期：2022-06-14
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