Efficient Quantification of Iloperidone in Simulated Nasal Fluid: UVSpectrophotometric Method Development and Validation

Introduction: Iloperidone, an atypical second-generation antipsychotic, is primarily used to treat schizophrenia through selective antagonism of dopamine D2 and serotonin 5-HT2A receptors. However, until now, no validated method has been reported for its quantification in simulated nasal fluid (SNF), which is essential for developing intranasal drug delivery systems for Iloperidone. This research focuses on the development and validation of a UV spectrophotometric method for the quantification of Iloperidone in SNF to support advancements in intranasal drug delivery systems of Iloperidone Method: The proposed analytical method adheres to ICH Q2(R1) guidelines, ensuring linearity, robustness, accuracy, and precision. Method development involved optimizing solvent composition to enhance drug solubility. The drug exhibited absorbance maxima at 228.5 nm. Validation parameters, including limit of detection (LOD) and limit of quantification (LOQ), recovery studies, and precision (intra-day and inter-day), were systematically evaluated. The study also employed commonly used metric systems for greenness evaluation of the developed method, AGREE and AGREEprep. Result: The results proposed the developed method for Iloperidone quantification in SNF to be linear over the concentration range of 5-70 µg/ml, with a high correlation coefficient of R² = 0.9965. Accuracy studies showed a recovery range of 99.07-100.42%, while precision results yielded %RSD values below 2 for both intra-day and inter-day analyses. Sensitivity was confirmed with LOD and LOQ of 2.40 µg/ml and 7.27 µg/ml, respectively. Robustness and repeatability evaluations further substantiated the reliability of the method. The developed method demonstrated high environmental compatibility, achieving AGREE and AGREEprep scores of 0.70 and 0.66, respectively, confirming its suitability as a green and sustainable analytical approach. Discussion: The developed UV spectrophotometric method offers a practical balance between analytical performance and environmental sustainability, serving as an eco-efficient alternative to more complex chromatographic methods like HPLC or LC-MS for early-stage formulation and quality control studies. Its simplicity, low solvent consumption, and validated greenness make it particularly advantageous for routine intranasal formulation screening, supporting sustainable pharmaceutical development while maintaining analytical accuracy and reliability. Conclusion: This validated UV spectrophotometric method is efficient, cost-effective, accurate, precise, and highly reproducible, making it suitable for routine quality control and analysis of Iloperidone in SNF. The findings contribute to the development of optimized intranasal delivery systems for Iloperidone, enhancing its therapeutic potential for central nervous system disorders.