Objectives: Pain medicine practitioners frequently use urine drug testing (UDT) to monitor adherence to opioid therapy. It can be difficult to interpret a result as normal or abnormal in relation to which opioid compounds are expected to be found in the urine. It is not commonly thought that morphine can be metabolized to hydromorphone. We investigated whether hydromorphone may be a metabolite of morphine normally appearing in UDT of patients prescribed morphine.

Methods: With IRB approval, this was a retrospective case-control study of urine toxicology results in chronic pain patients taking only morphine. We used gas chromatography mass spectroscopy (GCMS) urine screens, which are highly accurate with a false positive rate of <.5% for the presence of specific opioid compounds. Inclusion criteria included urine results positive for morphine only (controls) or morphine and hydromorphone (cases). Demographic and medical history variables, and any history of aberrant drug behavior were recorded and related to the presence or absence of hydromorphone in the urine.

Results: Hydromorphone was present in 21 cases and absent in 32 controls (66% prevalence rate), none of whom had a history of aberrant drug behavior. Positive cases were likely female, taking higher daily doses of morphine, and had higher urine morphine concentrations (p<.05). Only morphine urine concentration was a significant predictor of the hydromorphone metabolite in a logistic regression model (p<.05).

Conclusions: It is likely that hydromorphone is a minor metabolite of morphine, normally appearing in the UDT of patients taking morphine. This finding assists in determining whether a UDT result is normal or abnormal, and subsequently whether a patient is compliant with opioid therapy. This observation should be confirmed by a prospective study in a controlled environment. Variables such as gender, morphine dose, morphine urine concentration, and genetic determinants of morphine metabolism should be investigated further.