6-Monoacetylmorphine (6-MAM), Confirmation, Meconium
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Heroin (diacetylmorphine) is a semisynthetic opiate that is closely related to morphine. It is no longer used clinically in the United States, though it is used elsewhere for rapid relief of pain.(1) Like morphine and other opiates, its relaxing and euphoric qualities make heroin a popular drug of abuse. Heroin is commonly injected intravenously, although it can be administered by other means such as snorting, smoking, or inhaling vapors.
Heroin shares the core structure of morphine, with the addition of 2 acetyl groups, which are thought to enhance its permeation into the central nervous system.(2,3) Heroin is metabolized by sequential removal of these acetyl groups; loss of the first acetyl converts heroin into 6-monoacetylmorphine (6-MAM).(2,3) Heroin is rarely found in meconium since only 0.1% of a dose is excreted unchanged. 6-MAM is a unique metabolite of heroin, and its presence is a definitive indication of heroin use. Like heroin, 6-MAM has a very short half-life; however, its detection time in meconium, the first fecal material passed by the neonate, is uncharacterized. 6-MAM is further metabolized into morphine, the dominant metabolite of heroin, and morphine will typically be found in a specimen containing 6-MAM.
Opiates, including heroin, have been shown to readily cross the placenta and distribute widely into many fetal tissues.(4) Opiate use by the mother during pregnancy increased the risk of prematurity and being small for gestational age. Furthermore, heroin-exposed infants exhibit an early onset of withdrawal symptoms compared with methadone-exposed infants. Heroin-exposed infants demonstrate a variety of symptoms including irritability, hypertonia, wakefulness, diarrhea, yawning, sneezing, increased hiccups, excessive sucking, and seizures. Long-term intrauterine drug exposure may lead to abnormal neurocognitive and behavioral development as well as an increased risk of sudden infant death syndrome.(5)
The disposition of drug in meconium is not well understood. The proposed mechanism is that the fetus excretes drug into bile and amniotic fluid. Drug accumulates in meconium either by direct deposit from bile or through swallowing of amniotic fluid.(6) The first evidence of meconium in the fetal intestine appears at approximately the 10th to 12th week of gestation, and slowly moves into the colon by the 16th week of gestation.(7) Therefore, the presence of drugs in meconium has been proposed to be indicative of in utero drug exposure during the final 4 to 5 months of pregnancy, a longer historical measure than is possible by urinalysis.(6)
Detection of in utero drug exposure up to 5 months before birth
The presence of 6-monoacetylmorphine (6-MAM) in meconium is definitive for heroin use by the mother. However, the absence of 6-MAM does not rule-out heroin use, because of its short half-life.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because the results of this test may have legal ramifications, it is recommended that testing be performed using chain of custody. A kit including all the materials necessary to complete chain of custody is available to ensure the test results are appropriate for legal proceedings.
The short half-life of 6-monoacetylmorphine (6-MAM) may prevent its detection in heroin users.
6-MAM is metabolized to morphine, but the presence of morphine alone is not sufficient evidence to prove heroin use. 6-MAM is the only definitive metabolite of heroin.
Send frozen if possible. When refrigerated, a significant percentage of 6MAM will convert to morphine in less than 24 hours.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Positives are reported with a quantitative LC-MS/MS result.
6-MAM by LC-MS/MS: 5 ng/g
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Giovannelli M, Bedforth N, Aitkenhead A: Survey of intrathecal opioid usage in the UK. Eur J Anaesthesiol 2008;25:118-122
2. Principles of Forensic Toxicology. Second edition. Washington DC, AACC Press, 2003 pp 187-205
3. Goodman and Gilman's: The Pharmacological Basis of Therapeutics, 10th edition. New York, McGraw-Hill Professional, 2001 pp 590-592
4. Szeto HH: Kinetics of drug transfer to the fetus. Clin Obstet Gynecol 1993;36:246-254
5. Kwong TC, Ryan RM: Detection of intrauterine illicit drug exposure by newborn drug testing. Clin Chem 1997;43(1):235-242
6. Ostrea EM Jr, Brady MJ, Parks PM, et al: Drug screening of meconium in infants of drug-dependent mothers: an alternative to urine testing. J Pediatr 1989 Sep;115(3):474-477
7. Ahanya SN, Lakshmanan J, Morgan BL, Ross MG: Meconium passage in utero mechanisms, consequences, and management. Obstet Gynecol Surv 2005 Jan;60(1):45-56; quiz 73-74