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Updated: Jun 17, 2026

High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
Urine testing for norcodeine, norhydrocodone, and noroxycodone facilitates interpretation and reduces false
Edward J Cone1, Anne Zichterman, Rebecca Heltsley
1Johns Hopkins School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD 21224, USA. Edward.cone@comcast.net
Detecting unique opiate normetabolites like norcodeine, norhydrocodone, and noroxycodone in urine drug tests confirms parent drug use. This improves accuracy in pain patient monitoring by reducing potential false negatives.
Area of Science:
- Clinical Chemistry
- Forensic Toxicology
- Pharmacology
Background:
- Urine drug testing is crucial for monitoring pain patients' adherence, diversion, and illicit use.
- Interpreting semi-synthetic opiate tests is challenging due to complex metabolism and commercially available metabolites.
- Unique normetabolites (norcodeine, norhydrocodone, noroxycodone) are not commercially available, offering definitive markers of parent drug consumption.
Purpose of the Study:
- To evaluate the prevalence and patterns of three unique normetabolites: norcodeine, norhydrocodone, and noroxycodone.
- To assess the utility of these normetabolites in urine specimens from pain patients undergoing opiate therapy.
Main Methods:
- Urine specimens (N=2654) were hydrolyzed using beta-glucuronidase.
- A validated liquid chromatography tandem mass spectrometry (LC/MS/MS) assay was employed.
- Analysis targeted codeine, norcodeine, morphine, hydrocodone, norhydrocodone, hydromorphone, dihydrocodeine, oxycodone, noroxycodone, and oxymorphone with a 50 ng/mL limit of quantitation.
Main Results:
- Overall, 71.4% of specimens tested positive for one or more analytes.
- Prevalence of parent drugs: codeine (1.2%), hydrocodone (26.1%), oxycodone (36.2%).
- Prevalence of normetabolites: norcodeine (0.5%), norhydrocodone (22.1%), noroxycodone (31.3%).
- Normetabolites were detected in the absence of parent drugs in 8.6% (norcodeine), 7.8% (norhydrocodone), and 9.4% (noroxycodone) of cases.
- A significant proportion of these normetabolite-positive, parent-drug-negative specimens lacked other indicative metabolites.
Conclusions:
- The inclusion of norcodeine, norhydrocodone, and noroxycodone assays is valuable for interpreting opiate drug sources in patient monitoring.
- Testing for these unique metabolites can reduce potential false negatives in urine drug screens.
- This approach enhances the accuracy of assessing patient compliance and drug use patterns.
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