A solid-state ion-selective electrode for detection of tramadol has been fabricated utilizing polyaniline nanoparticles as an ion-toelectron transducer layer. The polyaniline (PANI) nanoparticles were synthesized by the micellar emulsion chemical polymerization method and the mean particle size was ∼8 nm. The inclusion of PANI nanoparticles as an ion-to-electron transducer layer between an ionophore-doped PVC membrane and solid contact electrodes was carried out to improve the stability of the electrical signal. Both short and long-term stability studies were performed and compared to PANI free electrodes. Furthermore, the electrode's stability at various pH levels was investigated. The formation of water at PANI/solid contact interface was studied. Results indicate an absence of the water layer at the interface. The PANI/solid contact electrodes had good piece-to-piece reproducibility and potential stability over 30 days. The fabricated electrodes were utilized for tramadol determination as a model pharmaceutical drug in the presence of all excipients; the linear range was 10 −6 to 10 −2 mol L −1 , pH stability range was from 3-7 and the detection limit was calculated to be 3.9 × 10 −7 mol L −1 . Fig. 1, is a centrally acting analgesic, used for treatment of moderate to severe pain and most types of neuralgia. It is a synthetic analogue of codeine but it is neither opiate-derived nor a nonsteroidal anti-inflammatory drug. 1 TM has agonist actions at the μ-opioid receptor and effects reuptake at the noradrenergic and serotonergic systems.Several methods have been employed for determination of TM in pharmaceutical formulations. These methods include non-aqueous titration with perchloric acid, 2,3 ultraviolet spectrophotometry, 4-6 high-performance liquid chromatography, 7-9 gas chromatography, 10 LC-MS/MS, 11 capillary electrophoresis, 12 HPTLC-densitometry, 13 voltammetry, 14 and ion-selective-based potentiometry. [15][16][17][18][19][20] The selectivity of ion-selective electrodes permits direct analysis of the analyte activity even in a complex sample without prior separation or sample preparation, such as K + and Na + determination in blood samples. The conventional liquid contact electrodes, where the ion selective membrane is sandwiched between the sample solution and the inner filling solution, have certain inherent limitations such as mechanical complexity (i.e., high risk of solution leakage and the need for maintenance), the conventional miniaturized electrodes are fragile, and there is possibility of primary ion leaching between both internal and external solutions. In these regards, solid contact ion selective electrodes (SC-ISEs) should offer simple, rigid, and robust sensors, moreover, their compatibility with microfabrication processes allow the mass fabrication of cost-effective sensors. Nevertheless, SC-ISEs suffer from high potential drift and irreproducibility of the standard potential with time due to the difficulty of interfacing an ion-conducting sensing membrane with the electron-conducting ...