Standard Drug Screening Fails to Identify Some Children Who Have Been Exposed to Substances in Unsafe Home Environments
The study highlights an adjustment that clinical labs can make to improve the accuracy of results
CHICAGO — According to research presented today at ADLM 2025 (formerly the AACC Annual Scientific Meeting & Clinical Lab Expo), standard drug screening misses low concentrations of targeted substances in around 5 percent of urine samples taken from patients under age 18, suggesting that children with drugs in their systems are sometimes released from healthcare settings into unsafe home environments. The study highlights an adjustment that clinical labs can make to improve the accuracy of results and to help ensure that substance-exposed children and their families get appropriate support.
Researchers have long known that standard urine drug screening (UDS)—which is typically done using a technique known as immunoassay—can sometimes trigger false positives, or erroneous results that indicate the presence of a drug when there isn’t one. It’s the reason a second confirmatory test with mass spectrometry is typically used to verify results for patients who test positive on immunoassay.
However, the opposite issue, where UDS indicates an absence of drugs in patients who have actually taken them (false negatives), has not been well studied. This mistake is more likely to occur in samples taken from infants and young children whose kidneys are still developing or who have incidental exposure to a low level of drugs, resulting in a low drug concentration in their urine that may not reach the cutoff used in standard UDS. One approach for minimizing this possibility is to use mass spectrometry on all pediatric patients, skipping the initial immunoassay.
“To our knowledge, St. Louis Children’s is the only hospital in the US to adopt this ‘direct-to-mass-spectrometry’ approach,” said Dr. Yanchun Lin, one of the study’s authors and a clinical chemistry fellow at Washington University in Saint Louis, Missouri. “So we really want to urge laboratorians to reconsider the approach they adopt for pediatric UDS testing.”
The researchers used two strategies to compare immunoassay results with mass spectrometry for detecting substances in common drug tests, including amphetamine/methamphetamine, cocaine/benzoylecgonine (the main metabolite of cocaine), THC, opiates, fentanyl, benzodiazepines, and methadone. In the first approach, they studied 125 urine samples over a 5-month period from pediatric patients with weakly positive results on mass spectrometry to check how many of them were missed by immunoassay (forward approach). For the second strategy, they assessed 115 urine samples that tested negative on immunoassay to assess if mass spectrometry could detect any drugs (reverse approach).
Among the 125 samples that tested positive on mass spectrometry, 112 (approximately 90 percent) contained compounds not detected by immunoassay, most commonly methamphetamine and benzoylecgonine. Thirty-eight (33 percent) of the 115 samples found negative on routine UDS tested positive for at least one substance when re-examined by mass spectrometry. Moreover, mass spectrometry identified substances in six samples (5 percent) that were targeted but missed by immunoassay.
In addition, the researchers identified 32 pediatric urine samples that contained prescription medications not picked up by immunoassay, including lorazepam, ketamine, bupropion, methylphenidate, clonidine, quetiapine, venlafaxine, and naloxone. They also found five samples containing fentanyl, which wasn’t on the UDS menu at some study centers from which samples were taken.
Taken together, the results indicate that UDS may miss low drug concentrations in approximately 1 in 20 pediatric urine samples. This finding held true using both the forward and reverse schemes, spanning multiple clinical environments and analytic platforms. Using a direct-to-mass spectrometry approach would significantly lessen the risk of false-negative drug screens and largely eliminate false-positive findings as well, the authors conclude.
That said, making this change isn’t without challenges for labs. “It’s actually pretty labor intense,” Lin said, “and it’s much harder to maintain the assay” using the direct-to-mass spectrometry approach. “You need highly trained personnel and dedicated full-time employees,” she added.
But labs that can make the shift will benefit from more accurate results that could translate to better care. “If it’s possible, it should definitely be adopted, especially for pediatric patients,” Lin said.
Session information
Abstract A-349: False-negative immunoassay drug screens uncovered with a direct to mass spectrometry approach in a pediatric population will be presented during:
Student poster competition on Monday, July 28 at 9:30 am–4 pm, Room S405
Scientific poster session on Tuesday, July 29 at 9:30 am–5 pm (presenting authors in attendance from 1:30–2:30 pm), Poster Hall on the Expo show floor
Both sessions will take place at McCormick Place, Chicago.