Rapid and sensitive fluorescence detection of clozapine via g-C₃N₄ nanosheet-based quenching

Clozapine (CLZ), as an efficient atypical antipsychotic drug, faces significant challenges in clinical application, such as a narrow treatment window and huge pharmacokinetic differences between individuals. Therefore, developing sensitive and reliable detection methods for CLZ is crucial for ensuring therapeutic efficacy and reducing medication risks. Strongly blue-fluorescent g-C₃N₄ nanosheets (g-C₃N₄Ns) were successfully prepared from bulk g-C₃N₄ through a two-step process involving protonation and subsequent ultrasonic exfoliation. Leveraging the charge-transfer-induced dynamic quenching of their fluorescence by CLZ, we developed a sensitive analytical method using these nanosheets as a fluorescent probe. The experimental results indicate that this method exhibited a wide linear range (0.02-500 µM) and a low detection limit of 3 nM. When applied to the analysis of bovine serum and clozapine tablets, the spiked recovery rate of CLZ was within the range of 92.0-104.7%, with a relative standard deviation (RSD) of less than 5%, and the results were satisfactory. Moreover, the probe demonstrated excellent selectivity and anti-interference capability against multiple potential interferents. In summary, the g-C₃N₄Ns fluorescence sensing platform developed herein integrates rapid response, high sensitivity, and excellent reliability and has been successfully applied to CLZ detection in complex matrices. This work establishes a solid foundation for future applications in real human plasma samples and ultimately serves therapeutic drug monitoring (TDM).