A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities

•Study results highlighted the potential of CAD in creating the environment for utilization of green solvents as acetonitrile alternatives in RP-HPLC.•Derringer's desirability function enabled simple and sped-up development and optimization of RP-HPLC methods for separation of risperidone and structurally related impurities with either ethanol or acetone, as organic modifier.•According to constructed GAPI pentagrams RP-HPLC methods with either ethanol or acetone as organic modifier could be evaluated towards their “greenness”, and recommendation for usage of these solvents could be done. Green analytical chemistry is primarily directed towards minimization of the amount of waste associated with either the sample preparation or analysis. Among different chromatographic methods, liquid chromatography is considered the least green, allowing for various possibilities for greening. Using green solvents such as ethanol or acetone in RP-HPLC, as an alternative to acetonitrile, is recently attracting an attention. Both ethanol and acetone are characterized with low toxicity, with certain drawbacks limiting their regular use in RP-HPLC. Ethanol has low eluotropic strength and causes high backpressures, while acetone shows high UV cut-off, making it unsuitable for UV/Vis detection. To overcome the existing problems, Corona Charged Aerosol Detector was employed for development of RP-HPLC methods for separation of risperidone and its structurally related impurities with either ethanol or acetone as organic modifier. The methods were optimized by experimental design methodology, while optimal conditions for separation were determined using Derringer's desirability function. Detailed assessment of 3D surface plots of Derringer's desirability function enabled selection of 0.6 mL min−1 flow rate and 20% (v/v) organic modifier content as optimal when using ethanol, while in case of acetone mobile phase flow rate was 0.8 mL min−1 and organic modifier content 17% (v/v). Methods were validated and their eco-friendly character was confirmed through Green Analytical Procedure Index (GAPI). Although both methods are ecologically acceptable, the main drawback is reflected in the fact that no recycling or another waste treatment method exist. In the end, acetone was prioritized over ethanol, due to lower health hazard and decreased amount of generated waste. [Display omitted]