Using liquid chromatography with tandem mass spectrometry (LC-MS/MS), researchers identified hydrocodone and morphine as metabolites in oral fluid in patients prescribed codeine. These are the findings of a new study published in Therapeutic Drug Monitoring

In the retrospective analysis of oral fluid drug testing results, LC-MS/MS was used to determine the prevalence rates in oral fluid for codeine and three codeine metabolites: morphine, norhydrocodone, and hydrocodone. Oral fluid samples were collected and submitted to Millennium Health for routine drug analysis. 

Related Articles

Codeine was the primary analyte detected in oral fluid after the use of codeine, keeping consistent with previous research. In codeine-positive samples, hydrocodone was detected in 68.4%, morphine in 18.4%, and norhydrocodone in 6.3% of samples. Concentrations of these analytes ranged from 1–>2000ng/mL for codeine, 1.0–20.2ng/mL for morphine, 1–740ng/mL for hydrocodone, and 2.1–47.5ng/mL for norhydrocodone. 

Hydrocodone was the most commonly detected metabolite in oral fluid samples testing positive for codeine with reported prescriptions for codeine. This is in contrast to urine samples where hydrocodone is typically present as a minor metabolite of codeine. 

Findings from the study can help improve the interpretation of oral fluid testing that is used to monitor opioid-prescribed patients. The study also suggests that clinicians should be cautious when interpreting hydrocodone positives in oral fluid results, as the use of codeine may be a possible explanation for hydrocodone positives.

Maria Guevara, PharmD, director of clinical affairs, education, and training, Millennium Health, added, “In a clinical context, it could mean that a clinician does not falsely accuse a patient of having taken a concomitant medication.”

For more information visit