Evaluation of a Non-Functionalized Fiber Taper-Based Mach–Zehnder Interferometer for Bulk Refractive-Index Monitoring Using Paracetamol as a Model Solute

Accurate monitoring of composition-related changes in concentrated pharmaceutical streams is relevant to process control and quality assessment. Here, we experimentally demonstrate a non-functionalized fiber taper-based Mach–Zehnder interferometer (MZI) as a bulk refractive-index sensor using paracetamol solutions as a controlled model system. The sensing mechanism is based on changes in the bulk refractive index of the surrounding medium, which are correlated with paracetamol concentration in controlled aqueous samples prepared using either a paracetamol standard or commercial tablets. Wavelength tracking of the MZI transmission spectra over 0–12.5 mg/mL paracetamol, corresponding to a refractive-index range of 1.333–1.335 RIU, yielded a sensitivity of 233 pm/(mg/mL) and 1497.3 nm/RIU, with a limit of detection (LOD) of 1.08 mg/mL. An intensity-based interrogation provided an average absolute sensitivity of 5.73 × 10−6 W/(mg/mL), a practical resolution of 44.2 mg/L, and an improved LOD of 75.6 mg/L. Additionally, an MZI configuration in reflection, evaluated using reagent-grade paracetamol standard solutions, yielded a wavelength sensitivity of 318 pm/(mg/mL), while phase tracking of reflected spectra yielded a sensitivity of −97.4 mrad/(mg/mL). These results demonstrate the versatility, linearity, repeatability, temporal stability, and low-maintenance operation of the MZI for bulk refractive-index monitoring, confirming its performance under controlled model system conditions.