Characterization and origin differentiation of morphine derivatives by DSC/TG and FTIR analysis using pattern recognition techniques

Abstract

Important narcotic analgesic active pharmaceutical ingredients (APIs): morphine hydrochloride (MoH), morphine sulfate (MoS) and the starting substance for their semi-synthesis morphine base (MoB), have been characterized by thermoanalytical methods (DSC and TG/DTG) and Fourier transform infrared spectroscopy (FTIR). Additionally, a set of different pattern recognition techniques were used to reveal the differentiation features of the morphine fingerprints obtained from 28 API samples (6 MoS, 9 MoH and 13 MoB) from known origin in order to build a predictive model for authentication of samples of unknown composition. It was observed that important parameters for building pattern recognition model using thermoanalytical data are the same analytical information significant for structural characterization: melting point (observed on DSC curves) and thermal degradation point (observed on TG curves). Hierarchical cluster analysis (HCA), based on these reproducible features, allowed identification of the different MoB and MoS samples origin. However, due to the absence of the characteristic endothermic phenomenon originating from the melting of MoH samples, the required characteristic fingerprinting features were not obtained. The FTIR–ATR spectroscopy study clearly confirmed that the different morphine entities can be easily identified by their infrared signature when spectra are collected without sample preparation in order to preserve the original information about the corresponding molecular structures. However, FTIR analysis showed low discriminatory power for authenticity check of morphine and its derivatives with respect to their different origins, but proved inevitable to detect the ‘genuine’ falsification.