In clinical anesthesia, precise dosing depends on feedback from blood drug concentrations. However, rapid tools for measuring these concentrations are currently limited. This study evaluated the capability of a novel portable mass spectrometer (CELL) to rapidly quantify etomidate and dexmedetomidine in rat plasma. The 50% effective dose (ED50) of both drugs was determined using the up-and-down method. CELL's methodology was validated according to standard guidelines. Linear regression and intraclass correlation coefficient (ICC) analyses were conducted to assess the consistency between CELL and HPLC-MS measurements. The ED50 of etomidate was found to be 0.9 mg/kg and that of dexmedetomidine was 21.1 μg/kg in rats. For etomidate, CELL demonstrated linearity in the range of 210-2,000 ng/ml (y = 427.0x - 30,526, R2 = 0.995) with a limit of quantitation (LOQ) of 210 ng/ml. For dexmedetomidine, linearity was observed in the range of 6-1,000 ng/ml (y = 14,669x + 109,875, R2 = 0.997) with an LOQ of 6 ng/ml. In the mixed group, etomidate showed linearity in the range of 100-2,000 ng/ml (y = 431.4x + 11,864, R2 = 0.996) with an LOQ of 100 ng/ml, while dexmedetomidine exhibited linearity in the range of 5-1,000 ng/ml (y = 14,141x + 52,430, R2 = 0.997) with an LOQ of 5 ng/ml. A strong linear correlation was observed between CELL and HPLC-MS. These results indicate that CELL provides excellent performance in the rapid and simultaneous quantification of both drugs, supporting real-time monitoring to meet diverse clinical requirements. This approach has strong potential for point-of-care (POC) monitoring in perioperative veterinary and human anesthesia.