目的 探究建立基于细胞响应谱的中药注射剂质量评控方法，以最大限度预警中药注射剂质量波动，保障中药注射剂临床用药安全。方法 收集注射用双黄连（冻干）不同批次正常样品和过期样品及临床发生不良反应样品，同时制备3批特殊样品（光照、暴露、高温）。建立注射用双黄连（冻干）的细胞响应谱并提取关键参数，进行相似度、聚类分析和主成分分析，以筛检质量波动样品。结果 以大鼠嗜碱性细胞白血病RBL-2H3细胞为模式细胞，注射用双黄连（冻干）正常样品为模式药物，建立了注射用双黄连冻干细胞响应谱，并提取脱附时间（ΔT）、曲线下面积（AUC）、抑制率（I₁₂，I₂₄）、相似度为特征参数，进行量化分析，通过细胞响应谱法在25批注射用双黄连（冻干）样品中共检出不合格样品21批，细胞响应谱法不仅可有效区分正常样品和特殊样品，而且还能将高温组、光照组和过期样品有效区分，但是不能将开放环境组和不良反应组样品分开。结论 细胞响应谱方法能更全面、灵敏、准确地发现中药注射剂质量波动差异，可作为制剂通则检查和化学指纹谱检测的有益补充，提高中药注射剂产品质控水平。

Objective To explore and establish a quality assessment and control method of traditional Chinese medicine (TCM) injections based on cell response spectrum, so as to maximize early warning of the quality fluctuation of TCM injections and ensure the safety of TCM injections. Methods Different batches of normal samples, expired samples and samples with adverse reaction in clinic of Shuanghuanglian Lyophilized Injection [注射用双黄连 (冻干), SHL] were collected, and three batches of special samples (light, exposure, high temperature) were prepared at the same time. The cell response spectrum of SHL was established and key parameters were extracted. Similarity, cluster analysis and principal component analysis were performed to screen the quality fluctuation samples. Result With RBL-2H3 cells as model cells and normal samples of SHL as model drug, the response spectrum of freeze-dried SHL was established, and characteristic parameters such as desorption time (ΔT), area under the curve (AUC), inhibition rate (I₁₂, I₂₄) and similarity were extracted for quantitative analysis. A total of 21 batches of unqualified samples were detected in 25 batches of SHL samples by cell response spectrum method. Cell response spectrometry could not only effectively distinguish normal samples from special samples, but also distinguish high temperature group, light group and expired samples, but could not separate open environment group and adverse reaction group samples. Conclusion The cell response spectrum method can detect the quality fluctuation difference of TCM injections more comprehensively, sensitively and accurately, and can be used as a useful supplement for the inspection of preparation general rules and chemical fingerprint spectrometry, so as to improve the quality control level of TCM injections.

R285.52

北京中医药大学基本科研业务费项目资助（2022-JYB-XJSJJ-079）；中药毒性理论与安全用药传承创新团队（ZYYCXTD-C-202005）