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Test Catalog

Test ID: 6MAMM    
6-Monoacetylmorphine (6-MAM), Confirmation, Meconium

Useful For Suggests clinical disorders or settings where the test may be helpful

Detection of in utero heroin exposure up to 5 months before birth

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 it 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)

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.

Negative

Positives are reported with a quantitative liquid chromatography-tandem mass spectrometry result.

Cutoff concentration: 5 ng/g

Interpretation Provides information to assist in interpretation of the test results

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

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.

Clinical Reference Recommendations for 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. 2nd ed. AACC Press; 2003:187-205

3. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. 10th ed. McGraw-Hill; 2001:590-592

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

8. Langman LJ Bechtel LK, Meier BM, Holstege C: Clinical toxicology. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:832-887

9. Baselt RC: Disposition of Toxic Drugs and Chemical in Man. 10th ed. Biomedical Publications; 2014