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Opiates: Morphine

Metabolism
  • Morphine is primarily metabolized by glucuronidation to morphine-3-glucuronide which comprises about 75% of the total morphine dose.
  • Glucuronidation to morphine-6-glucuronide accounts for a much smaller percentage of the dose but is an active metabolite.
  • About 5% of the morphine dose is converted to normorphine by loss of a methyl group.
  • Normorphine is further metabolized to normorphine glucuronide.
  • A small portion of the morphine dose is metabolized to hydromorphone by dehydrogenation. (R-C-OH R-C=O).
Morphine has a half-life of 1.5 to 6.5 hours. And can be detected in urine for 2 to 3 days after ingestion.
Interpretation
  • Less than 10% of morphine is excreted as morphine. The remainder is excreted as conjugates. In confirmation testing, a sample preparation step called hydrolysis is used to break the glucuronide bond to convert the glucuronides back to free morphine.
  • Positive morphine drug tests can be due to the ingestion of codeine, morphine, or 6-AM.
  • If the presence of morphine is due to morphine ingestion only, morphine alone will usually be detected in the urine.
  • With high doses of morphine, hydromorphone may also be detected.
  • Hydromorphone will generally be detected at less than 2.5% of the morphine concentration.
  • If hydromorphone is detected at levels greater than 25% of morphine, then the hydromorphone is most likely due to separate use of hydromorphone.
  • It is also possible to detect low levels of codeine in the urine of patients taking a high dose of morphine. As previously discussed, codeine, in these cases, is probably present as a manufacturing impurity.
  • Consumption of poppy seeds or an herbal tea containing Papivaris fructus can yield a positive morphine and codeine result on a urine drug test.
  • If morphine is detected at concentrations greater than 1,000 ng/mL and the morphine to codeine ratio is less than 2:1, the use of poppy seeds as the sole source for a positive test can be ruled out.
  • If codeine is detected at concentrations greater than 300 ng/mL and the morphine to codeine ratio is less than 2:1, the use of poppy seeds can be ruled out; the presence of codeine is attributed to codeine ingestion.