Islatravir Dimer: Crystal Form Dependence of a Radiation-Induced Degradation Product

A rare
example of crystal form-dependent, gamma radiation-induced
degradation is presented. Islatravir is known to exist in several
polymorphic forms, but only one of these forms shows the generation
of a specific dimer degradation product under gamma irradiation. Extended
gamma irradiation studies demonstrated that only one of the known
crystalline forms shows an appreciable rate of dimer formation. Additionally,
this dimer is not observed to form under other forced stress conditions.
We present the structural elucidation of this dimer impurity and rationalize
its form-dependent generation based on the analysis of the underlying
crystal structure.