拉曼光谱法在快速筛查紫杉醇脂质体制剂中的应用

Application of Raman spectroscopy on the rapid screening of paclitaxel liposome preparation

目的应用拉曼光谱法建立定性鉴别模型,实现紫杉醇脂质体制剂的现场快速筛查。方法隔包装采集注射用紫杉醇脂质体的拉曼光谱,使用主成分分析(PCA)算法去除包装的干扰信号,提取紫杉醇脂质体的拉曼信号,用经典最小二乘(CLS)建立定性鉴别模型。对模型进行正向验证和反向验证确定判别的阈值,模型输出的相关系数值同阈值比较进行定性判定。使用外标法实现方法在三种仪器上的转移。结果排除玻璃包装的干扰提取的光谱与直接测量的光谱相关系数达0.9744,建立的紫杉醇脂质体定性模型,判断阈值为0.85,正向验证(脂质体制剂)和反向验证(脂质体膜成分和紫杉醇)结果均为通过。通过使用传递光谱和峰位检索,方法能够在便携式拉曼光谱仪、傅里叶拉曼光谱仪和显微成像拉曼光谱仪上实现转移。结论本研究所建立的快速筛查方法可满足抗癌类贵重药品的现场和实验室快速筛查,为监管和公安打假提供一种科学有效的手段。

Objective To realize the rapid screening on site, Raman spectroscopy was applied to establish an identification model of paclitaxel liposome preparation. Methods Raman spectra of the whole paclitaxel liposome product with package were first collected, and principal component analysis（PCA） algorithm was then used to extract paclitaxelliposome signals from the identified signals. Classic least squares（CLS） algorithm was used to established the identification model. The threshold was determined by the positive validation and negative challenge tests, and identification results would be get by compare the the correlation coefficients with the threshold. External standard method was utilized to realize the model transfer on three different kinds of Raman spectrometer. Results The correlation coefficient between the extracted spectrum and directly-measured spectrum was 0.9744. The paclitaxelliposome identification model was built with a threshold of 0.85, and results of both positive validation and negative challenge tests were all passed. Model transfer results also indicated that with the use of transfer spectra and peak search, the method established could be used on portable Raman, microscope imaging Raman and FT-Raman spectroscopes. Conclusion The Raman method established in this study could realize expensive anticarcinogen both on-site non-invasively and laboratory use, which can provide a scientific and efficient means for regulation and crackdown on counterfeit expensive medicine.