Advanced LC-MS/MS method for selective quantification of nitrosamine impurities in Risperidone: Enhancing drug safety

In the current study, a simple, rapid, and sensitive analytical method was developed and validated for the determination and quantification of four nitrosamine drug substance-related impurities (NDSRIs) in Risperidone drug substance. Chromatographic separation was achieved on an ACE-5 PFP C18 column (150 mm × 4.6 mm × 3 µm) using gradient elution with 0.2 % formic acid and methanol. The method utilized a flow rate of 0.8 mL/min, an injection volume of 5 µL, and a column temperature of 40 °C. Positive electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode was used for quantification. The limit of detection (LOD) and limit of quantification (LOQ) ranged from 0.12 to 0.46 and 0.23–0.93 µg/mL, respectively. The calibration curves for NDIRs impurities (0.23–185.72 µg/mL) exhibited R² values between 0.998 and 0.999. Recoveries ranged varied from 94.9 to 124.4 %, with % RSD < 15.0 %. The results indicated that the method is reliable for monitoring all NINA, NBOP, NBP, and NB impurities in Risperidone.