Parts-per-Million Detection of Trace Crystal Forms Using AF-PTIR Microscopy
Parts-per-Million Detection of Trace Crystal Forms Using AF-PTIR Microscopy
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DOI：
10.1021/acs.analchem.2c02358
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发表时间：
2022-09-13
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;Simpson，Garth J.
自体荧光检测光热中红外（AF-PTIR）显微镜显示能够检测γ-吲哚美辛样品中的α-吲哚美辛杂质（百万分之一）。两种吲哚美辛晶体多晶型物的UV-自发荧光的光热响应的细微差异被用于基于指纹区域中红外光谱的亚微米化学鉴别。AF-PTIR分配由二次谐波产生（SHG）显微镜独立确认，这表明通过快速识别合适的视场来减少总分析时间。AF-PTIR显微镜有可能帮助在固体剂型开发管道中早期鉴定晶体形式杂质。
Autofluorescence-detected photothermal mid-infrared (AF-PTIR) microscopy was shown to enable parts-per-million detection of α-indomethacin impurity in γ-indomethacin samples. Subtle differences in the photothermal response of the UV-autofluorescence of two indomethacin crystal polymorphs were used for sub-micron chemical discrimination based on fingerprint region mid-IR spectroscopy. The AF-PTIR assignment was independently confirmed by second harmonic generation (SHG) microscopy, which was shown to reduce the total analysis time by rapidly identifying the suitable fields of view. AF-PTIR microscopy has the potential to assist in the early identification of crystal form impurities in the solid dosage forms development pipeline.