Compliance or Abuse? Detectable hydromorphone in patients taking oxycodone

Abstract A middle-aged woman with recent cervical diskectomy with spinal fusion at C3-C4 suffered a mechanical fall with bilateral upper extremity paresthesia requiring admission but no surgical intervention. Patient was seen by orthopedic service and was recommended to continue using Aspen collar and oxycodone for pain. Following discharge, a drug urine screen test was performed, and showed positive for oxycodone by immunoassay. Confirmatory urine test by liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed detectable oxycodone, oxymorphone and hydromorphone. In patients treated with opioid therapy for chronic pain, urine drug monitoring is an important tool to ensure that patients are adhering to the prescribed medication. Hydrocodone and hydromorphone are not metabolites of oxycodone. However, hydrocodone can be present in oxycodone preparations with an estimated impurity of <1%. Hydrocodone can be metabolized into hydromorphone, although, there is no literature reporting detectable hydromorphone in patients’ urine with prescribed oxycodone only. This case resulted in a quality improvement project where we evaluated the detection of hydrocodone and hydromorphone in positive oxycodone urine samples using LC-MS/MS. We analyzed 322 oxycodone positive urine samples. Twenty-one samples (6%) had detectable hydrocodone and/or hydromorphone below 100 ng/mL. Twelve out of the 21 were from patients taking no opioid medication other than oxycodone in the last week, with 33.3% showing detectable hydromorphone and 75% for hydrocodone below 100 ng/dL. The calculated hydrocodone/oxycodone (HC/OC) and hydromorphone/oxycodone (HM/OC) ratios were on average 0.26% HC/OC = 0.26% (0.05-0.69% SD 0.002; HM/OC = 0.26% (0.18-0.37% SD 0.001)] each (<1%). Patients taking oxycodone and other opioids had ratios >1% [HC/OC = 168% (3-563% SD 2.53; HM/OC = 699% (1.09-6585% SD 15.96)] and had higher detected levels (>100 ng/mL). Pain management can be very challenging; therefore, laboratory testing provides an objective assessment of drug exposure and adherence to treatment. Cut-off values for considering positive the detection of hydrocodone and hydromorphone may change the interpretation of the drug urine tests in patients with prescribed oxycodone. Using higher cutoff (100 ng/mL) and the ratios HC/OC and HM/OC (<1%) may be useful to determine that the detection of these components is due to impurity of oxycodone formulation.