Detecting maternal prenatal opiate/opioid use up to 5 months before birth
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Codeine
Dilaudid (Hydromorphone)
Heroin (as Morphine)
Hycodan (Hydrocodone)
Hydrocodone (Hycodan, Vicodin)
Hydromorphone (Dilaudid, Vicodin)
Lortab (Hydromorphone)
Morphine
Opiates
Oxycodone (Oxycontin, Percodan)
Vicodin (Hydrocodone)
Meconium
For chain-of-custody testing, order OPTMX / Opiate 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: Collect entire random meconium specimen.
If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.
0.3 g (approximately 1/4 teaspoon)
Grossly bloody | Reject; Pink OK |
Stool Diapers | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Meconium | Frozen (preferred) | 28 days | |
Refrigerated | 28 days | ||
Ambient | 14 days |
Detecting maternal prenatal opiate/opioid use up to 5 months before birth
Opiates are naturally occurring alkaloids that are derived from the opium poppy and demonstrate analgesic effects. Opioids are derived from natural and semisynthetic alkaloids of opium or synthetic compounds(1):
-Codeine is a naturally occurring opioid agonist often incorporated into formulations along with acetaminophen or aspirin to increase its analgesic effect.(2) Codeine is metabolized to morphine and subsequently undergoes glucuronidation and sulfation.
-Morphine is an opioid receptor agonist used for major pain analgesia.(2) It has been shown to distribute widely into many fetal tissues(3) and has been detected in meconium.
-Hydrocodone is a semisynthetic analgesic derived from codeine. Hydrocodone is 6 times more potent than codeine and is prescribed for treatment of moderate-to-moderately severe pain.(2) Hydrocodone undergoes O-demethylation in vivo, forming hydromorphone.
-Hydromorphone, a semisynthetic derivative of morphine, is an opioid analgesic. It is 7 to 10 times more potent than morphine, its addiction liability is similar to morphine.(2)
-Oxycodone, a semisynthetic narcotic derived from thebaine. It is metabolized by O-demethylation, forming oxymorphone.(2)
-Oxymorphone is a semisynthetic opioid derivative of thebaine and is indicated for moderate-to-severe pain.(2)
-Heroin, a semisynthetic derivative of morphine, is rapidly deacetylated in vivo to the active metabolite 6-monoacetlymorphine (6-MAM), which is further hydrolyzed to morphine.(2)
Opiates have been shown to readily cross the placenta and distribute widely into many fetal tissues. Opiate use by the mother during pregnancy increases the risk of prematurity and small size for gestational age. Furthermore, heroin-exposed infants exhibit an early onset of withdrawal symptoms compared to methadone-exposed infants. These infants demonstrate a variety of symptoms, including irritability, hypertonia, wakefulness, diarrhea, yawning, sneezing, increased hiccups, jitteriness, 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.
The disposition of opiates and opioids in meconium, the first fecal material passed by the neonate, 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 deposition from bile or through swallowing of amniotic fluid. 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. 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.
Negative
Positives are reported with a quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) result.
Cutoff concentrations for LC-MS/MS testing:
Codeine: 20 ng/g
Hydrocodone: 20 ng/g
Hydromorphone: 20 ng/g
Morphine: 20 ng/g
Oxycodone: 20 ng/g
Oxymorphone: 20 ng/g
The presence of any of the following opiates (codeine, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone) at 20 ng/g or greater or 6-monoacetlymorphine at 10 ng/g or greater indicates the newborn was exposed to opiates/opioids during gestation.
No significant cautionary statements
1. Gutstein HB, Akil H: Opioid analgesics. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. McGraw-Hill; 2006
2. Baselt RC: Disposition of Toxic Drugs and Chemical in Man. 10th ed. Biomedical Publications; 2014
3. Szeto HH: Kinetics of drug transfer to the fetus. Clin Obstet Gynecol. 1993 Jun;36(2):246-254
4. Ahanya SN, Lakshmanan J, Morgan BLG, Ross MG: Meconium passage in utero: mechanisms, consequences, and management. Obstet Gynecol Surv. 2005 Jan;60(1):45-56
5. 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
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.
80361
80365
G0480 (if appropriate)
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
OPATM | Opiate Confirmation, M | 69026-3 |
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.
|
---|---|---|
31848 | Morphine | 69027-1 |
31850 | Oxymorphone | 69028-9 |
31849 | Hydromorphone | 68541-2 |
31847 | Codeine | 68542-0 |
31852 | Oxycodone | 68543-8 |
31851 | Hydrocodone | 68544-6 |
31868 | Interpretation | 8215-6 |
31869 | Chain of Custody | 77202-0 |