Schmitt Paul D, Trasi Niraj S, Taylor Lynne S, Simpson Garth J
†Department of Chemistry and ‡Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States.
Mol Pharm. 2015 Jul 6;12(7):2378-83. doi: 10.1021/acs.molpharmaceut.5b00065. Epub 2015 Jun 24.
Second harmonic generation (SHG) microscopy was used to rapidly identify regions of interest for localized confocal Raman spectroscopy measurements in order to quantify crystallinity within lyophilized Abraxane powder (protein bound paclitaxel for injectable suspension). Water insoluble noncentrosymmetric crystalline particles ranging from ∼1 to 120 μm were identified by SHG, with wide variability in crystal size and frequency observed between several batches of Abraxane. By targeting the Raman analysis to these localized regions identified by SHG, the required measurement time was decreased over 2 orders of magnitude, from 8 h to 2 s. Experimental Raman spectra of SHG active domains in Abraxane were in good agreement with experimental spectra of pure crystalline paclitaxel. These collective results are consistent with up to 30% of the active ingredient being present as poorly soluble crystalline particulates in some batches of Abraxane.
二次谐波产生（SHG）显微镜用于快速识别感兴趣区域，以进行局部共聚焦拉曼光谱测量，从而量化冻干的艾力雅（注射用蛋白结合紫杉醇）粉末中的结晶度。通过SHG识别出了尺寸范围约为1至120μm的水不溶性非中心对称晶体颗粒，在几批艾力雅之间观察到晶体大小和频率存在很大差异。通过将拉曼分析靶向SHG识别出的这些局部区域，所需的测量时间减少了2个数量级以上，从8小时降至2秒。艾力雅中SHG活性域的实验拉曼光谱与纯结晶紫杉醇的实验光谱高度吻合。这些总体结果表明，在某些批次的艾力雅中，高达30%的活性成分以难溶性结晶颗粒的形式存在。
