School of Physics and Astronomy, 6123University of Nottingham, Nottingham, UK.
113460GlaxoSmithKline, Stevenage, UK.
Appl Spectrosc. 2023 Mar;77(3):246-260. doi: 10.1177/00037028221139494. Epub 2022 Nov 16.
Quantitative analysis of drug delivery with in biological systems is an integral challenge in drug development. Analytical techniques are important for assessing both drug target delivery, target action, and drug toxicology. Using mimetic tissue models, we have investigated the efficacy of Raman spectroscopy in quantitative detection of alkyne group and deuterated drugs in rat brain and rat liver tissue models. Lasers with 671 nm and 785 nm wavelengths were assessed for their feasibility in this application due to opposing relative benefits and disadvantages. Thin tissue sections have been tested as a practical means of reducing autofluorescent background by minimizing out-of-focus tissue and therefore maximizing photobleaching rates. Alkyne-tagged drugs were quantitatively measured at 18 ± 5 μg/g drug/tissue mass ratio in rat brain and at 34 ± 6 μg/g in rat liver. Quantification calibration curves were generated for a range of concentrations from 0-500 μg/g. These results show the potential of Raman spectroscopy as a diffraction-limited spatially resolved imaging technique for assessing drug delivery in tissue applications.
在生物系统中进行药物输送的定量分析是药物开发中的一个重要挑战。分析技术对于评估药物靶标输送、靶标作用和药物毒理学都很重要。我们使用模拟组织模型,研究了拉曼光谱在定量检测大鼠脑和大鼠肝组织模型中炔基基团和氘代药物中的应用效果。由于相对优缺点相反,评估了波长为 671nm 和 785nm 的激光在该应用中的可行性。薄组织切片被测试为通过最小化离焦组织并因此最大化光漂白速率来减少自发荧光背景的实际手段。在大鼠脑中以 18 ± 5μg/g 药物/组织质量比定量测量了炔基标记药物,在大鼠肝中以 34 ± 6μg/g 定量测量。生成了从 0 到 500μg/g 浓度范围的定量校准曲线。这些结果表明,拉曼光谱作为一种用于评估组织应用中药物输送的衍射受限空间分辨成像技术具有潜力。