A Sensitive Electrochemical Sensor Based on Calix[n]arene-Modified PGE for the Determination of Tofacitinib in Human Urine Samples and Pharmaceutical Dosage Forms.

Tofacitinib is a potent Janus kinase inhibitor widely used in the treatment of various autoimmune diseases, including rheumatoid arthritis and psoriasis. Monitoring its concentration is vital for therapeutic efficacy and safety. In this study, a novel, rapid, and highly sensitive electrochemical sensing platform was developed for tofacitinib determination using pencil graphite electrodes (PGEs) modified with polypyrrole (PPy) and calix-[n]-arene derivatives. The modified electrodes were prepared via cyclic voltammetry (CV) by incorporating three different macrocycles: calix[4]-arene, calix[6]-arene, and calix[8]-arene. Surface characterization was performed using Scanning Electron Microscopy (SEM) and SEM-EDS. Under optimized conditions (Britton-Robinson buffer at pH 4.0, 5 polymerization cycles, and 0.005 M modifier concentration), tofacitinib was quantified using differential pulse voltammetry (DPV). The linear calibration ranges were established as 0.10-0.80 ppm for calix[4]-arene and calix[6]-arene, and 0.10-0.60 ppm for calix[8]-arene. The limits of detection (LOD) were found to be 0.0275, 0.0212, and 0.0184 ppm for calix[4], [6], and [8] derivatives, respectively, demonstrating a clear correlation between macrocyclic cavity size and analytical sensitivity. The proposed sensor exhibited excellent selectivity in the presence of common interferents like ascorbic acid, caffeine, and glucose. Furthermore, the practical applicability of the method was validated in pharmaceutical formulations and human urine samples, yielding satisfactory recovery values between 98.0% and 101.5%. This study provides a cost-effective and disposable alternative to sophisticated chromatographic methods for routine clinical analysis.