Venlafaxine as a dummy template for the synthesis of molecularly imprinted polymers for tramadol determination

A dummy-template molecularly imprinted polymer (MIP) for tramadol selective extraction was synthesized for the first time. The MIP, consisting of methacrylic acid (MAA) and ethylene glycol dimethacrylate (EDMA), was prepared on a filter paper support by photopolymerization. Venlafaxine was used as a dummy template because of its structural and chemical similarity to tramadol. This innovative strategy not only avoids template leakage but also overcomes the significant regulatory and economic limitations associated with using tramadol —a controlled and potentially abused substance— as a template. Furthermore, the paper-based photopolymerization approach enables the rapid synthesis of a surface-imprinted MIP layer on the support, which enhances accessibility to binding sites, improves mass transfer kinetics, and facilitates faster analyte recognition compared to conventional bulk MIPs. To achieve this purpose, the paper was pre-activated with benzophenone (BP) and EDMA, and incubated with the venlafaxine before the polymerization step. Non-molecular imprinted polymers (NIPs) were prepared using the same procedure without the template incubation step. The optimization of the synthesis variables, including the EDMA/MAA ratio, polymerization time, type of porogen, and concentration of venlafaxine, was carried out to find the best imprinting conditions. The final MIPs and corresponding NIPs were characterized by SEM. Moreover, the variables affecting the extraction procedure were optimized in order to improve the polymer sorbent capacity. HPLC-UV was employed for venlafaxine and tramadol identification and quantification. After optimization, MIPs presented an imprinting factor (IF) of 4.80 for venlafaxine (dummy template) and 4.70 for tramadol (target analyte), and a limit of detection (LOD) and a limit of quantification (LOQ) of 0.006 and 0.018 mg/L, respectively. The MIPs did not show a specific interaction with other drugs. The precision of the method, expressed as RSD (%), varied from 9.0 to 10.8 % (intra- and inter-day). MIPs were applied for tramadol extraction from human urine samples, obtaining recovery values of 95.0–95.7 %.