Small‐scale two‐dimensional liquid chromatography for a preparative re‐purification of a highly labile tritium‐labeled compound

Abstract

Tritium‐labeled compounds are generally less stable than their non‐labeled counterparts. This requires storage at low temperatures, a constant workflow of quality checks, and subsequent re‐purifications. As the amount of tritium‐labeled material is typically purified in the μg range, repeated injections on analytical‐scale ultra high‐performance liquid chromatography systems can provide high‐resolution re‐purification results. Yet, degradants can be undesirably included in the compound isolation because the amount of decomposition can vary dramatically depending on the structure. We report a case of a sensitive molecule that could not be isolated in pure form even though the chromatographic separation was successful. In this case, the use of a small‐scale two‐dimensional preparative liquid chromatography approach with a direct transfer interface to a second (trapping) column resulted in a highly pure compound (>98% radiochemical purity). This approach combines high chromatographic resolution, accurate control over the re‐purification process, minimal sample manipulation, and higher overall safety for the handling of radioactive samples.