Mass spectrometry in ocular drug research

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.

Transporter Protein Expression of Corneal Epithelium in Rabbit and Porcine: Evaluation of Models for Ocular Drug Transport Study

“…Targeted absolute quantification and untargeted global proteomics approaches have been used previously for studying protein expression of transporters, receptors, and enzymes in ocular barriers. − Transporter protein expression levels of OATP1B1 or BCRP, MRP1 or OCTN1 correlated with the transport activity. Quantitative analyses of transporter and enzyme expression have been conducted in human and porcine retinal pigment epithelium (RPE), as well as in a variety of ocular tissues in humans, respectively. ,,, Nevertheless, quantitative and global proteomics data for the CE are still lacking.…”