A multi-parameter calibration and analysis strategy has been developed based on the kinetics of charge transfer reactions. Absolute and ratiometric electrochemiluminescence signals are elucidated from single measurements for the detection of hydroxyzine and cetirizine as prototype drugs which greatly enhance the near-infrared electrochemiluminescence from atomically precise Au22 nanoclusters stabilized with lipoic acid ligands on ITO electrodes. The signal-on sensing mechanism eliminates the need for recognition elements and highly excess co-reactants in conventional electrochemiluminescence practice. The rates of sequential charge transfer reactions render specificity in electrochemiluminescence intensity and kinetics toward the target molecular/electronic structures and are conveniently controlled/optimized by operation parameters. Signal kinetic profiles, in stark contrast to steady-state or single-point recordings, not only improve the signal/noise ratio but also offer greater resolving power to differentiate analogue species and nonspecific interference. The fundamental kinetics-based ratiometric concept/strategy is not limited to a specific luminophore or a co-reactant and is thus generalizable. The case studies successfully detect and discriminate drug compounds at sub-nanomolar physiological ranges, with efficacy validated using synthetic urine toward point-of-care applications in therapeutic/abuse drug monitoring.