Label-Free Autofluorescence-Detected Mid-Infrared Photothermal Microscopy of Pharmaceutical Materials
Label-Free Autofluorescence-Detected Mid-Infrared Photothermal Microscopy of Pharmaceutical Materials
复制标题
药物材料的无标记自发荧光检测中红外光热显微镜
DOI：
10.1021/acs.analchem.1c05504
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发表时间：
2022
影响因子：
7.4
通讯作者：
Simpson, Garth J.
中科院分区：
文献类型：
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作者：
Razumtcev, Aleksandr;Li, Minghe;Rong, Jiayue;Teng, Chu C.;Pfluegl, Christian;Taylor, Lynne S.;Simpson, Garth J.
无标记自发荧光检测光热中红外 (AF-PTIR) 显微镜经过实验验证，并应用于测试活性药物成分 (API) 在含有代表性药物赋形剂的混合物中的分布。双光子激发紫外荧光 (TPE-UVF) 支持使用可见光光学器件的天然芳香族部分的自发荧光。荧光量子产率的热调制用于报告红外吸收，从而使指纹区域中的红外光谱具有由荧光决定的空间分辨率。 AF-PTIR 为芳香族 API 提供高选择性和高灵敏度的图像对比度，补充了基于折射率/散射光热调制的广泛适用的光学光热红外 (O-PTIR) 显微镜。绘制 API 分布图对于粉末剂型制造的设计流程至关重要，高空间差异可能会导致交付剂量和产品功效的变化。 API 候选物中芳香族部分的普遍存在表明 AF-PTIR 与 O-PTIR 结合的可行性，可提高空间异质剂型中化学分类的可信度。
Label-free autofluorescence-detected photothermal mid-IR (AF-PTIR) microscopy is demonstrated experimentally and applied to test the distribution of active pharmaceutical ingredients (APIs) in a mixture containing representative pharmaceutical excipients. Two-photon excited UV-fluorescence (TPE-UVF) supports autofluorescence of native aromatic moieties using visible-light optics. Thermal modulation of the fluorescence quantum yield serves to report on infrared absorption, enabling infrared spectroscopy in the fingerprint region with a spatial resolution dictated by fluorescence. AF-PTIR provides high selectivity and sensitivity in image contrast for aromatic APIs, complementing broadly applicable optical photothermal IR (O-PTIR) microscopy based on photothermal modulation of refractive index/scattering. Mapping the API distribution is critical in designing processes for powdered dosage form manufacturing, with high spatial variance potentially producing variability in both delivered dosage and product efficacy. The ubiquity of aromatic moieties within API candidates suggests the viability of AF-PTIR in combination with O-PTIR to improve the confidence of chemical classification in spatially heterogeneous dosage forms.