Anomalous observations of hydrocodone in patients on oxycodone

Urine drug monitoring is used by physicians treating chronic pain patients with opioid therapy. Patients are tested in part to insure that they are not taking other drugs. Therefore, the finding of hydrocodone in a patient who is only prescribed oxycodone has clinical implications. Oxycodone preparations are known to have small amounts of hydrocodone as an impurity estimated to be < 0.1%. We established the concentration of unexpected hydrocodone in patients taking oxycodone.

Urine drug testing specimens from a population of 30,000 pain patients prescribed oxycodone in various formulations were quantitatively measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The frequency and concentration of hydrocodone as a function of oxycodone concentration were determined.

There were 187 specimens with > 100,000 ng/ml of oxycodone. Of these, 72% were positive for hydrocodone. Of the 311 specimens with oxycodone concentrations > 50,000-100,000 ng/ml, 33% were positive for hydrocodone. Of the 1067 specimens with oxycodone > 20,000-50,000 ng/ml, 16% were positive for hydrocodone. Of the 8508 specimens with oxycodone > 1000-20,000 ng/ml, 16% were positive for hydrocodone.

The high frequency of hydrocodone in samples containing high concentrations of oxycodone was ascribed to the manufacturing process of the oxycodone medications. However, a significant number of patients also took hydrocodone that was not listed on their prescribed medications. When oxycodone is > 100,000 ng/ml, hydrocodone should be <1500 ng/ml. When oxycodone is < 100,000 ng/ml then hydrocodone should be <500 ng/ml. Values greater than these indicate non-prescribed hydrocodone use. Clinicians and laboratories testing urine for drugs should be aware of the possibility of low concentrations of hydrocodone in the urine of patients taking high doses of oxycodone.