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质谱分析法在眼科药物研究中的应用

Mass spectrometry in ocular drug research.

作者信息

Del Amo Eva M, Vellonen Kati-Sisko, Urtti Arto, Terasaki Tetsuya, Hammid Anam, Honkakoski Paavo, Auriola Seppo

机构信息

School of Pharmacy, University of Eastern Finland, Kuopio, Finland.

Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

出版信息

Mass Spectrom Rev. 2023 Aug 2. doi: 10.1002/mas.21861.

Abstract

Mass spectrometry (MS) has been proven as an excellent tool in ocular drug research allowing analyzes from small samples and low concentrations. This review begins with a short introduction to eye physiology and ocular pharmacokinetics and the relevance of advancing ophthalmic treatments. The second part of the review consists of an introduction to ocular proteomics, with special emphasis on targeted absolute quantitation of membrane transporters and metabolizing enzymes. The third part of the review deals with liquid chromatography-MS (LC-MS) and MS imaging (MSI) methods used in the analysis of drugs and metabolites in ocular samples. The sensitivity and speed of LC-MS make simultaneous quantitation of various drugs and metabolites possible in minute tissue samples, even though ocular sample preparation requires careful handling. The MSI methodology is on the verge of becoming as important as LC-MS in ocular pharmacokinetic studies, since the spatial resolution has reached the level, where cell layers can be separated, and quantitation with isotope-labeled standards has come more reliable. MS will remain in the foreseeable future as the main analytical method that will progress our understanding of ocular pharmacokinetics.

摘要

质谱(MS)已被证明是眼部药物研究中的一种出色工具,可对小样本和低浓度样本进行分析。本综述首先简要介绍眼生理学和眼部药代动力学,以及推进眼科治疗的相关性。综述的第二部分介绍眼部蛋白质组学,特别强调膜转运蛋白和代谢酶的靶向绝对定量。综述的第三部分涉及用于分析眼部样本中药物和代谢物的液相色谱 - 质谱(LC - MS)和质谱成像(MSI)方法。尽管眼部样本制备需要小心处理,但LC - MS的灵敏度和速度使得在微小组织样本中同时定量各种药物和代谢物成为可能。MSI方法在眼部药代动力学研究中即将变得与LC - MS一样重要,因为其空间分辨率已达到可分离细胞层的水平,并且使用同位素标记标准进行定量变得更加可靠。在可预见的未来,质谱仍将是推进我们对眼部药代动力学理解的主要分析方法。

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