In this work, a simple and accurate in vitro drug metabolism strategy was proposed by using macroporous ordered siliceous foam (MOSF) as a nanoreactor for confining the nanohybrid of CdTe quantum dots (QDs) and cytochrome P450 2D6 (CYP2D6). After CYP2D6 was coupled to QDs through the carbodiimide coupling chemistry, the resulting nanohybrid of CYP2D6/QDs exhibited fluorescence emission at 645 nm, which could be used as a photocatalyst for drug metabolism. The energy level of CYP2D6 was located between the conduction band (CB) and valence band (VB) of QDs, which provided the possibility of the electron transferring from the CB of QDs to CYP2D6. Tramadol was chosen as the model substrate. Under the irradiation of a white-light, the photocurrent increased with the addition of tramadol in a wide linear range from 4.0 mu M to 100 mu M. The apparent Michaelis-Menten constant was measured to be 3.6 mu M. The high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) confirmed the production of metabolite of o-desmethyltramadol. Such nanoreactor provided a suitable environment to confine a mass of enzyme, as well as to maintain their catalytic activities for highly effective drug metabolic reactions. This showed promising potential for immobilizing various enzymes and other biomolecules in biomimetic metabolism study. (C) 2016 Elsevier B.V. All rights reserved.