Determination of the absolute configuration of organic molecules is essential in drug development and the subsequent approval process. We show that this determination is possible through electron diffraction using nanocrystalline material. Ab initio structure determination by electron diffraction has so far been limited to compounds that maintain their crystallinity after a dose of one electron per square angstrom or more. We present a complete structure analysis of a pharmaceutical cocrystal of sofosbuvir and L-proline which is one order of magnitude less stable. Data collection at multiple crystal positions and a sophisticated method of intensity extraction allowed us to solve the ab initio structure. We further show that the dynamic diffraction effects are strong enough to allow a clear determination of the absolute structure of a material composed of light atoms.
