An Unusual Case of High 6-Monoacetylmorphine and Low Morphine in Urine: Heroin Abuse or Analytical Error?

Abstract

A 59-year-old male with a past medical history of chronic low back pain, opioid use disorder, and type 2 diabetes mellitus presented to an outpatient clinic for pain contract–related urine drug screen testing. Current medications included metformin, oxycodone, and Suboxone® (buprenorphine and naloxone combination). The patient stated that 5 days prior to the visit, he stopped taking Suboxone due to complaints of nausea and vomiting. Urine toxicology test results are summarized in Table 1. ... ... Suboxone is an opioid abuse management medication that is formulated with buprenorphine and naloxone. Naloxone has limited bioavailability when administered sublingually and should be barely detectable in urine. However, when Suboxone is taken parenterally, naloxone enters the blood stream and is largely excreted in urine. In this case, the presence of a high concentration of naloxone in urine with a high ratio to buprenorphine suggested parenteral administration (1). Heroin is readily metabolized into 6-MAM and then to morphine. Typically, the 6-MAM-to-morphine ratio is <0.26, so it is uncommon to see a high positive 6-MAM with very low morphine concentrations (2). The calculated 6-MAM-to-morphine ratio in this sample was 7.27. Conversion from morphine to 6-MAM due to contaminants in enzyme hydrolysis or acid hydrolysis used during sample preparation in urine samples with extremely high morphine (>100 000 μg/L) has been reported (3). In our case, morphine was very low, so this was unlikely, but to rule out any analytical cause, the positive urine sample was sent to a reference laboratory, which confirmed our findings. The fact that 2 laboratories using different mass spectrometry–based methods showed detectable 6-MAM supported heroin use, instead of a false positive due to an interference. The unusually low morphine result in some heroin users has been reported elsewhere and may be mostly attributed to inhibitors of carboxylesterases from the heroin synthesis process (2) or explained by polymorphism in the esterase enzymes metabolizing 6-MAM to morphine (4). The physician also requested serum fentanyl testing by mass spectrometry 5 days after the original urine sample collection (fentanyl was not part of our general urine drug screen), which came back positive for fentanyl and norfentanyl. In addition to the unexpected positive amphetamine result, all of this confirmed that this patient suffered from polysubstance abuse.