Simultaneous determination of hydromorphone, hydrocodone and their 6α‐ and 6β‐hydroxy metabolites in urine using selected ion recording with methane chemical ionization

A selected ion recording using chemical ionization (methane) is described for the simultaneous measurement of hydrocodone, hydromorphone and their respective 6α‐ and 6β‐hydroxymetabolites in human urine. The samples were acid‐hydrolyzed, extracted and derivatized by silylation. Only partial resolution of the components on 3% OV‐17 was achieved but was sufficient for their determination. The [M+1]⁺ ions of the drugs and metabolites as well as the [M+29]⁺ ion of the internal standard were recorded. The assay was sensitive down to c. 0.01 μ g ml⁻¹. The relative standard deviation of standards processed along with the samples ranged from 4.5–8.2%. Hydrocodone was found to be metabolized in man primarily by O‐demethylation and 6‐keto reduction. Hydromorphone was excreted mainly in the unchanged form (after acid‐hydrolysis) with only minor amounts of the 6‐hydroxymetabolites being detected. A lack of stereoselectivity in the metabolic reduction of hydrocodone was observed.