Pharmaceutical analysis using broadband terahertz quantum cascade laser sources based on difference frequency generation

We present a pharmaceutical analysis method for quantitative evaluation of theophylline polymorphism, based on a terahertz difference-frequency quantum cascade laser source (THz DFG-QCL). In the experiments, samples consisting of an additive and hydrous or anhydrous theophylline were used as model drugs. The absorbance of the samples was obtained by illuminating them with a THz DFG-QCL producing broadband THz emission. While no correlation was found between the anhydrate concentration and absorbance, a significant correlation was observed for the hydrate concentration $(\mathbf{R}^{2}=\mathbf{0.92})$ From the results, our system successfully evaluated pseudo-polymorphism of theophylline despite requiring no complicated optical system.