Morphine is a Schedule II drug that exists as a natural alkaloid in the plant Papaver somniferum and is prescribed under the following trade names: Astramorph, Avinza, DepoDur, Duramorph, Kadian, Kapanol, MS Contin, MSIR, Oramorph and Roxanol 1,2. Morphine is a µ receptor agonist, which causes a reduction in asyclic adenosine monophosphate, an increase of intracellular potassium concentration, and cell membrane hyperpolarization3. Continued use may lead to tolerance and addiction2,3.
Morphine is administered subcutaneously, intramuscularly, intravenously, or as an intrathecal injection with a typical dose of 1-10 mg/kg; however it can also be administered orally with a typical dose of 2-200 mg2.
Morphine is highly distributed throughout the body; however due to first-pass metabolism, only 20-40% is bioavailable3. The half-life of morphine is 1.3 - 6.7 hours with the peak serum concentration averaging around 0.8-1.6 hours for a single 30 mg oral dose2.
Morphine is primarily metabolized by glucurindation as well as N-dealkylation to form pharmacologically inactive morphine-3-glucuronide (M3G), pharmacologically active morphine-6-glucuronide (M6G), and normorphine, respectively. Additionally, a minor metabolite, hydromorphone may be present in chronic pain management patients prescribed morphine. Morphine is also a metabolite of codeine, ethylmorphine, heroin and pholcodine.
Morphine is largely excreted through the bile with significant enterohepatic circulation of morphine and its metabolites. Up to 87% of the dose is excreted in urine as conjugates, with 75% present as M3G, within 72 hours. Additionally, a small percentage of the drug conjugate is excreted through the feces2.
The opiate screening methodology utilized for the detection of morphine and metabolites is the Enzyme Immunoassay (EIA) with a cutoff concentration of 300 ng/mL. Qualitative and quantitative confirmation is performed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) with at the cutoff concentration of 20 ng/mL. The urine samples are hydrolyzed prior to analyses and total morphine (morphine, M3G, M6G) concentration is reported.
Morphine lacks major metabolites other than the glucuronides; therefore, typically only morphine should be present in urine from patients prescribed this drug. In chronic pain management patients, it is possible to detect the minor metabolite hydromorphone5. In a study completed by Heltsley et al. a total of 2704 patients were positive for morphine and out of these 333 specimens contained hydromorphone (12.3%)6.
Interpretations of drug analysis reports should be conducted with caution and utilize the complete medical history of the patient. 6-Acetylmorphine (6-AM) is a metabolite of heroin and rapidly metabolizes to morphine. Morphine is also a metabolite of codeine and can account for 15% of codeine metabolites excreted in urine. Typically, codeine is present at a higher concentration than morphine2. Additionally, the ingestion of poppy seeds may cause a positive morphine, but morphine concentrations are usually below 1000 ng/mL7.