RESUMEN
This work presents an analytical method based on terahertz-time domain spectroscopy (THz-TDS) and partial least squares (PLS) regression models to quantify mebendazole (MBZ) polymorphs (forms A, B and C) in pharmaceutical raw material. Mebendazole polymorphs A, B and C were quantified with RMSEP values of 1.5% w/w, 1.2% w/w and 1.8% w/w, respectively. The limits of detection (LOD) ranges obtained with the best PLS regression models were 2.7-4.3% w/w, 2.9-4.0% w/w and 2.4-3.1% w/w, for polymorphs A, B and C, respectively. This analytical performance is better than those for the methods described in the literature using near (NIR) and middle (MIR) infrared spectroscopies. The main advantage of THz spectroscopy is its ability to access directly information related to crystal lattices. According to the results, the developed method is a powerful technique for the quantification of MBZ polymorphs in raw material. This methodology can be implemented as a Process Analytical Technology (PAT) tool for quality control of pharmaceutical feedstock.
RESUMEN
Terahertz dual frequency comb spectroscopy (THz-DFCS) yields high spectral resolution without compromising bandwidth. Nonetheless, the resolution of THz-DFCS is usually limited by the laser repetition rate, which is typically between 80 MHz and 1 GHz. In this paper, we demonstrate a new method to achieve sub-repetition rate resolution in THz-DFCS by adaptively modifying the effective laser repetition rate using integrated Mach-Zehnder electro-optic modulators (MZ-EOMs). Our results demonstrate that it is possible to improve the 100 MHz resolution of a terahertz frequency comb by at least 20x (down to 5 MHz) across the terahertz spectrum without compromising the average output power, and to a large extent, its bandwidth. Our approach can augment a wide range of existing THz-DFCS systems to provide a significant and easily adaptable resolution improvement.