Impurities in a morphine sulfate drug product identified as 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine.

Stability testing of morphine sulfate formulated with nonpareil sugar seeds (consisting of sucrose and starch) and fumaric acid revealed the formation of the three impurities 5-(hydroxymethyl)-2-furfural, 10-hydroxymorphine and 10-oxomorphine. 5-(Hydroxymethyl)-2-furfural was isolated via semipreparative HPLC utilizing volatile mobile phase constituents and was identified by analysis of its HRMS and NMR spectra. 10-Hydroxymorphine and 10-oxomorphine were obtained via semipreparative HPLC and subsequent removal of ion-pair reagents using an anion exchange resin, or by solid phase extraction, and identified by spectroscopic analysis followed by comparison with authentic materials.