Background/Objectives: Fluvoxamine (FLU) is a selective serotonin reuptake inhibitor
and one of the most potent agonists of the sigma-1 receptor. Emerging evidence shows
that FLU exerts protective effects in multiple organs, making it a promising candidate
for topical ocular therapy. Developing an FLU eyedrop for glaucoma can address a significant
treatment gap with potentially fewer side effects compared with conventional therapies.
To optimise formulation development, precise quantification of FLU in ocular compartments
such as aqueous humour, as well as systemic circulation, is essential to characterise
drug absorption, ocular bioavailability, and safety. Methods: We developed and validated
a UHPLC-MS method for FLU detection in aqueous humour and serum using simple sample
preparation steps. Results: The 11-min-long reverse phase chromatography followed
by SRM-based mass spectrometry detection provides a highly selective and sensitive
FLU detection method. Our method was proved to be linear in the 0.0625–1.5 µg/mL range
and was validated according to the EMA guidelines. Conclusions: The simplicity of
sample preparation, the tolerable matrix effects, and the favourable detection parameters
provide a robust tool for preclinical pharmacokinetic and pharmacodynamic studies
of FLU’s ocular protective effects.
