Is morphine positive in urine in a patient taking Tylenol 3 (acetaminophen and codeine) normally?

From the Guidelines

Yes, it is normal for someone taking Tylenol 3 to test positive for morphine in a urine drug test. Tylenol 3 contains codeine, which is metabolized by the body into morphine, as explained in the study published in the Journal of the National Comprehensive Cancer Network in 2019 1. When you take Tylenol 3 as prescribed, your body converts some of the codeine into morphine, morphine-3-glucuronide, and morphine-6-glucuronide, which then appear in your urine. This process is largely through the action of the cytochrome P450 enzyme, CYP2D6, and can vary between individuals due to polymorphism.

Some key points to consider:

• The metabolism of codeine to morphine can result in varying levels of morphine in the urine, depending on the individual's metabolic rate and other factors.
• It is essential to inform the testing facility or medical provider beforehand that you are taking Tylenol 3 with a valid prescription, to avoid any misinterpretation of the test results.
• The detection window for morphine in urine can vary, but it is typically 2-4 days after taking codeine-containing medications like Tylenol 3, as influenced by factors such as dosage, frequency of use, metabolism, hydration level, and kidney function, as noted in the context of opioid metabolism 1.

Given the information from the study 1, it is clear that the presence of morphine in the urine of a patient taking Tylenol 3 is an expected finding and does not necessarily indicate illicit drug use. Patients taking Tylenol 3 should be aware of this potential outcome and take steps to inform their healthcare providers and testing facilities accordingly.

From the Research

Morphine in Urine of Patients Taking Tylenol 3

• Tylenol 3 contains acetaminophen and codeine, and codeine is known to be metabolized to morphine in the body 2.
• A study found that morphine preparations can have small amounts of codeine as an impurity, estimated to be about 0.04% 3.
• However, the presence of morphine in urine can also be due to the metabolism of codeine, which is a component of Tylenol 3 2.
• The concentration of morphine in urine can vary depending on several factors, including the dose and duration of codeine use, as well as individual differences in metabolism 4, 5.

Detection of Morphine in Urine

• Morphine can be detected in urine using various methods, including thin-layer chromatography (TLC) 6, gas chromatography-mass spectrometry (GC-MS) 4, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) 2.
• The cutoff values for detecting morphine in urine can vary depending on the laboratory and the specific testing method used, but a common cutoff value is 2000 ng/mL 4.
• The presence of morphine in urine can be confirmed by detecting its metabolites, such as morphine-3-glucuronide and morphine-6-glucuronide 2.

Interpretation of Urine Test Results

• The interpretation of urine test results for morphine can be complex and requires consideration of various factors, including the patient's medical history, medication use, and individual differences in metabolism 5.
• A positive result for morphine in urine does not necessarily indicate illicit drug use, as it can also be due to the metabolism of codeine or other prescription medications 3, 2.
• Clinicians and laboratories should be aware of the potential for cross-reactivity and false positives when interpreting urine test results for morphine 3, 4.