Detection of in utero heroin exposure up to 5 months before birth
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
6-MAM (6-Monoacetylmorphine)
Acetylmorphine
Diacetylmorphine (Heroin)
Heroin Metabolite
Meconium
For chain-of-custody testing, order MAMMX / 6-Monoacetylmorphine (6-MAM) Confirmation, Chain of Custody, Meconium.
Supplies: Stool container, Small (Random), 4 oz (T288)
Container/Tube: Stool container
Specimen Volume: 1 g (approximately 1 teaspoon)
Collection Instructions:
1. Collect entire random meconium (newborn's first bowel movements) specimen.
2. Send specimen frozen.
Additional Information: When refrigerated, a significant percentage of 6-monoacetylmorphine (MAM) will convert to morphine in less than 24 hours.
If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.
0.3 g (approximately 1/4 teaspoon)
Bloody | Pink OK; Gross Reject |
Stool; diapers | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Meconium | Frozen | 14 days |
Detection of in utero heroin exposure up to 5 months before birth
Heroin (diacetylmorphine) is a semisynthetic opiate that is closely related to morphine. It is no longer used clinically in the
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
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)
Negative
Positives are reported with a quantitative liquid chromatography-tandem mass spectrometry result.
Cutoff concentration: 5 ng/g
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 and stability.
The short half-life and stability 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.
1. Giovannelli M, Bedforth N, Aitkenhead A: Survey of intrathecal opioid usage in the UK. Eur J Anaesthesiol. 2008;25:118-122
2. Levine B, ed. Principles of Forensic Toxicology. 4th ed. AACC Press; 2013
3. Brunton LL, Hilal-Dandan R, Knollmann BC, eds. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill; 2018
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. 12th ed. Biomedical Publications; 2020
Meconium is mixed with internal standard and extracted with methanol. The methanolic extract is further processed by solid phase extraction. The extract is analyzed by liquid chromatography tandem mass spectroscopy.(Unpublished Mayo method)
Monday through Sunday
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
80356
G0480 (if appropriate)
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
6MAMM | 6-MAM Confirmation, M | 29345-6 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
31874 | 6-Monoacetylmorphine | 29345-6 |
31875 | Interpretation | 69050-3 |