The Elusive Structure of Levocetirizine Dihydrochloride Determined by Electron Diffraction

Levocetirizine is an orally administrated, second-generation antihistaminic active pharmaceutical ingredient that has been used to treat symptoms of allergy and long-term hives for over 25 years. Despite the wide use of this compound, its crystal structure has remained unknown. Here we report the application of 3D electron diffraction (3D ED)/Micro-crystal electron diffraction (MicroED) to determine the crystal structure of Levocetirizine dihydrochloride directly from crystalline powders that were extracted from commercially available tablets containing the compound. We also showcase the utility of dynamical refinement to unambiguously assign absolute configuration. The results highlight the immense potential of 3D ED/MicroED for structure elucidation of components of microcrystalline mixtures that obviates the need to grow large-size single crystals and the use of complementary analytical techniques, which could be important for identification as well as for primary structural characterization.

Automated summary

In this study, the crystal structure of Levocetirizine dihydrochloride was determined directly from crystalline powders extracted from commercially available tablets using 3D electron diffraction (3D ED)/MicroED technique. The results highlight the immense potential of 3D ED/MicroED for structure elucidation of components of microcrystalline mixtures, eliminating the need for growing large-size single crystals and using complementary analytical techniques, which is important for identification and primary structural characterization.