EnvironmentalAssessment and Retrospective RiskAssessment of AStability-Indicating, Robust, Validated Liquid Chromatographic Method For Lumateperone Tosylate

Reliable quality control of lumateperone tosylate requires an analytical procedure that combines reproducible performance with practical laboratory operation and consideration of environmental impact. This study evaluated an isocratic reversed phase high performance liquid chromatographic method, alongside retrospective risk assessment and complementary greenness metrics. Chromatography was performed using a Kromasil C18 column (150 × 4.6 mm, 5 µm) with potassium dihydrogen orthophosphate buffer and acetonitrile (60:40, v/v), a flow rate of 1.0 mL/min, and a column temperature of 30 °C. Photodiode array detection was conducted at 245 nm within a seven minute run. Calibration concentrations covered 10.5–63 µg/mL. Repeat injection and 24 hour precision yielded relative standard deviations of 0.68% and 0.92%, respectively. Recoveries ranged from 99.17% to 101.18%, with a mean of 100.31%. Reported detection and quantification limits were 0.22 and 0.66 µg/mL. System suitability showed approximately 2,814 theoretical plates and a mean tailing factor of 1.71. Deliberate changes in flow rate, mobile phase composition, and temperature produced relative standard deviations of 0.200.50%. Retrospective risk assessment identified mobile phase composition and sample preparation as priorities for analytical control. Environmental evaluation yielded reported AGREE and Analytical Eco-Scale scores of 0.55 and 91, respectively, reflecting different assessment frameworks.