HPLC-UV法测定聚乙烯醇滴眼液中的有关物质含量

doi:10.5246/jcps.2025.05.033

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (5): 432-442.DOI: 10.5246/jcps.2025.05.033

HPLC-UV法测定聚乙烯醇滴眼液中的有关物质含量

李永菲, 高文分, 刘继华, 李哲媛, 李志远^*()

云南省食品药品监督检验研究院, 工业和信息化部产业技术基础公共服务平台, 云南昆明 650106

收稿日期:2024-12-09 修回日期:2025-02-10 接受日期:2025-03-08 出版日期:2025-06-02 发布日期:2025-06-01
通讯作者: 李志远

Quantitative analysis of related substances in polyvinyl alcohol eye drops using HPLC-UV

Yongfei Li, Wenfen Gao, Jihua Liu, Zheyuan Li, Zhiyuan Li^*()

Yunnan Institute for Food and Drug Control, Industrial Technology Basic Public Service Platform of the Ministry of Industry and Information Technology, Kunming 650106, Yunnan, China

Received:2024-12-09 Revised:2025-02-10 Accepted:2025-03-08 Online:2025-06-02 Published:2025-06-01
Contact: Zhiyuan Li
Supported by:
National Drug Sampling Inspection Project (No. NMPA Drug Admin [2024] 1).

摘要/Abstract

摘要：

聚乙烯醇滴眼液的现行质量标准中缺少有关物质检查项, 但原辅料中的杂质会影响产品安全, 为强化药品质量控制, 确保药物安全, 考察药品中有关物质的情况, 本研究采用HPLC-UV法对药品中的有关物质进行测定。该方法选择H型阳离子色谱柱, 通过方法学验证并对4家企业共116批次聚乙烯醇滴眼液及2批次原研样品进行检测。仅A企业及原研0.4 mL样品中检出甲酸, 含量均小于0.002%, 所有企业样品中均检出乙酸, 含量在0.1%以内。该方法专属性强、灵敏度高, 适合于聚乙烯醇滴眼液中甲酸、乙酸的含量测定, 甲酸来源于辅料, 乙酸来源于原料及生产过程pH调节时产生。虽然制剂中杂质含量整体较低, 由杂质带来的药品风险较低, 但仍建议企业关注。

关键词: 聚乙烯醇滴眼液, 有关物质, 甲酸, 乙酸

Abstract:

The current quality standard for polyvinyl alcohol eye drops lacks an impurity assessment, despite the potential impact of raw material impurities on product safety. To strengthen quality control and ensure drug safety, an investigation into the impurity profile of the formulation was conducted, and an HPLC-UV method was developed for impurity quantification. The method validation was performed using an H-type cation exchange column. A total of 116 batches of polyvinyl alcohol eye drops from four manufacturers and two batches of the innovator drug were analyzed. Formic acid was detected exclusively in 0.4 mL samples from Company A and the innovator drug, with concentrations below 0.002% in both cases. Acetic acid was identified in samples from all manufacturers, with levels not exceeding 0.1%. The method demonstrated high specificity and sensitivity, making it well-suited for the quantification of formic and acetic acids in polyvinyl alcohol eye drops. The presence of formic acid was attributed to excipients, whereas acetic acid originated from raw materials and was further generated during pH adjustment in manufacturing. Although the overall impurity levels were low and posed minimal risk to drug safety, manufacturers should remain vigilant regarding impurity control to maintain product quality.

Key words: Polyvinyl alcohol eye drops, Related substances, Formic acid, Acetic acid

Supporting:

李永菲, 高文分, 刘继华, 李哲媛, 李志远. HPLC-UV法测定聚乙烯醇滴眼液中的有关物质含量[J]. 中国药学(英文版), 2025, 34(5): 432-442.

Yongfei Li, Wenfen Gao, Jihua Liu, Zheyuan Li, Zhiyuan Li. Quantitative analysis of related substances in polyvinyl alcohol eye drops using HPLC-UV[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(5): 432-442.

图/表 14

Figure 1. Typical chromatogram of blank solvent/negative sample.

Figure 2. Typical chromatogram of the mixed standard solution of formic acid and acetic acid.

Figure 3. Typical chromatograms of the test sample solutions from various companies.

Table 1. Linear relationship of formic acid and acetic acid impurities.

Table 2. Results of the repeatability test.

Table 3. Results of the recovery test.

Table 4. Results of solution stability determination.

Table 5. Statistical table of the determination results of formic acid and acetic acid.

Figure 4. Statistical graph of acetic acid content in polyvinyl alcohol eye drops from various companies.

Figure 5. Trend graph of acetic acid content changes in the stability test.

Table 6. Results of the polyvinyl alcohol destructive test.

Figure 6. Typical chromatogram of the test sample solution in the raw material destruction experiment (high temperature, alkaline destruction, and acidic destruction).

Table 7. Results of the study on the relationship between acetic acid content and pH stability in polyvinyl alcohol eye drops (in past tense).

Figure 7. Trend chart for the stability study of pH value in polyvinyl alcohol eye drops.

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HPLC-UV法测定聚乙烯醇滴眼液中的有关物质含量

Quantitative analysis of related substances in polyvinyl alcohol eye drops using HPLC-UV

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