MeRgeION: a Multifunctional R Pipeline for Small Molecule LC-MS/MS Data Processing, Searching, and Organizing.

Small molecule structure elucidation using tandem mass spectrometry (MS/MS) plays a crucial role in life science, bioanalytical, and pharmaceutical research. There is a pressing need for increased throughput of compound identification and transformation of historical data into information-rich spectral databases. Meanwhile, molecular networking, a recent bioinformatic framework, provides global displays and system-level understanding of complex LC-MS/MS data sets. Herein we present meRgeION, a multifunctional, modular, and flexible R-based toolbox to streamline spectral database building, automated structural elucidation, and molecular networking. The toolbox offers diverse tuning parameters and the possibility to combine various algorithms in the same pipeline. As an open-source R package, meRgeION is ideally suited for building spectral databases and molecular networks from privacy-sensitive and preliminary data. Using meRgeION, we have created an integrated spectral database covering diverse pharmaceutical compounds that was successfully applied to annotate drug-related metabolites from a published nontargeted metabolomics data set as well as reveal the chemical space behind this complex data set through molecular networking. Moreover, the meRgeION-based processing workflow has demonstrated the usefulness of a spectral library search and molecular networking for pharmaceutical forced degradation studies. meRgeION is freely available at: https://github.com/daniellyz/meRgeION2.

Capillary electrophoresis-mass spectrometry in impurity profiling of pharmaceutical products.

Generally reversed-phase high-performance liquid chromatography (RP-HPLC) methods are extensively applied during quality control of pharmaceutical products. Since capillary electrophoresis (CE) is based on a different separation principle and consequently results in a unique selectivity compared to RP-HPLC, it can advantageously be used as an orthogonal technique. CE equipped with a mass spectrometer detector provides even more information that can be helpful for identification and structural elucidation purposes. CE-MS was recently implemented in the method development approach to support impurity profiling of pharmaceutical products. In this paper the application of CE-electrospray ionization (ESI)-MS/MS to the impurity profiling of galantamine hydrobromide in stressed Reminyl Extended Release (ER) capsules is discussed. Reminyl ER samples were stressed at different storing conditions. The impurity profile of these samples was compared with the current RP-HPLC and chiral CE method, but also with CE-ESI-MS/MS. The combination of these three methods provided valuable data that allowed understanding comprehensively the impurity profile of these samples. Two impurities were detected at concentrations lower than 0.05%, which did not occur in nonstressed samples. Chromatographic data and the fragmentation patterns of galantamine and related compounds were also examined for identification of these two degradation products.

Optimization and validation of an enantioselective method for a chiral drug with eight stereo-isomers in capillary electrophoresis.

Highly selective capillary electrophoresis (CE) screening methods were applied to find a satisfactory separation of a chiral drug with eight stereoisomeric compounds. The initial separation conditions were further optimized using response surface modelling by applying a Box-Behnken experimental design. This approach resulted in a rapid and efficient optimization of the buffer concentration, the concentration of two cyclodextrins, and the run voltage, in order to obtain final separation conditions of the method. Further optimization and validation of the system in terms of sensitivity and robustness resulted in a method that is suitable for quality control release purposes.