Hydromorphone and hydrocodone interference in GC/MS assays for morphine and codeine

The specificity of a GC/MS assay of morphine and codeine was examined with particular regard to the potential interference due to hydromorphone and hydrocodone, compounds that cross-react extensively in opiate screening tests. A GC/MS method with solid-phase extraction and acetylation or trimethylsilylation was used. The equilibrium between keto and enol forms of the potential interferents was evaluated. Sodium borohydride was tried as a means for converting potential interferents into products that are more clearly separated from morphine and codeine. It was found that borohydride reduction proceeded easily and led to products that could be distinguished from morphine and codeine. Moreover, the quantitation of morphine in the presence of hydromorphone was improved if the borohydride step was included in the analysis.