Detection of Hydrocodone and Morphine as Metabolites in Oral Fluid by LC-MS/MS in Patients Prescribed Codeine

Ther Drug Monit. 2017 Feb;39(1):88-90. doi: 10.1097/FTD.0000000000000365.


A retrospective analysis of oral fluid drug testing results using LC-MS/MS was performed to determine the prevalence rates in oral fluid for codeine (COD) and 3 COD metabolites-morphine (MOR), norhydrocodone (NHC), and hydrocodone (HCOD). Oral fluid samples were collected using Quantisal oral fluid collection device (Immunalysis Inc.) and submitted to Millennium Health, LLC for the routine drug analysis by LC-MS/MS. Consistent with previously published literature, COD was the primary analyte detected in oral fluid after the use of COD. In COD-positive samples, HCOD, MOR, and NHC were detected at rates of 68.4%, 18.4%, and 6.3%, respectively. Concentration ranges of these analytes were 1.0 to >2000 ng/mL for COD, 1.0-20.2 ng/mL for MOR, 1.0-740.0 ng/mL for HCOD, and 2.1-47.5 ng/mL for NHC. In contrast to urine, where HCOD is typically detected as a minor metabolite of COD, HCOD was the most commonly detected metabolite in oral fluid in samples testing positive for COD with reported prescriptions for COD. This observation suggests that care should be taken when interpreting HCOD positives in oral fluid results, and that the use of COD should be considered as one possible explanation for HCOD positives.

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacokinetics*
  • Chromatography, Liquid / methods*
  • Codeine / administration & dosage
  • Codeine / pharmacokinetics*
  • Humans
  • Hydrocodone / analogs & derivatives
  • Hydrocodone / analysis
  • Hydrocodone / metabolism
  • Morphine / analysis
  • Morphine / metabolism
  • Retrospective Studies
  • Substance Abuse Detection / methods
  • Tandem Mass Spectrometry / methods*


  • Analgesics, Opioid
  • norhydrocodone
  • Hydrocodone
  • Morphine
  • Codeine