Are false-positive phencyclidine immunoassay instant-view multi-test results caused by overdose concentrations of Ibuprofen, metamizol, and dextromethorphan?

To the Editor: We recently observed 3 occurrences of false-positive results for phencyclidine (PCP) on pediatric urine sample processing with the Instant-View multitest ‘‘drugs of abuse’’ panel (Alfa Scientific Designs, Poway, CA, USA). This is a solidphase immunoassay for qualitative detection of several drugs/drug metabolites in human urine. The drugs/drug classes covered by the Instant-View are amphetamine (cutoff, 1000 ng/mL), cocaine (cutoff, 300 ng/mL), methamphetamine (cutoff, 500 ng/mL), morphine (cutoff, 300 ng/mL), D-tetrahydrocannabinol (cutoff, 50 ng/mL), and, finally, PCP (cutoff, 25 ng/mL). Patient A was a 36-month-old boy. He was admitted to the emergency department for generalized seizures. Physical examination revealed emesis, diplopia, ataxia, and hypotonia, without fever. Laboratory test findingsdincluding a biochemical profile, electrolyte values, and results of urinalysis and serologies for human immunodeficiency virus, hepatitis C virus, hepatitis B surface antigen, Toxoplasma, rubella, and syphilisdwere within normal limits or negative. Patient B was a newborn female. She was admitted to the neonatal unit a few hours after delivery for hypoglycemia, apneas, and hypotonia. The baby was born at 41 weeks of gestation from a 37-year-old mother without prenatal monitoring. Apgar scores were 9/10/10, and all laboratory tests, including that for pH of cord blood, were unrevealing. Patient C was a 24-month-old girl. She was admitted to the emergency department because of ataxia and generalized seizures. Physical examination revealed depressed consciousness (Glasgow score, 12), repetitive and jerky movements of limbs with associated hyperreflexia and muscle rigidity, and dilated and unreactive pupils. The examination findings were otherwise unremarkable. In laboratory analyses, urine samples from these subjects were routinely tested for drugs of abuse with the InstantView multitest. Apart from toxicological screening positivity for PCP, the urine specimens from patient A and patient B were negative for all other drugs routinely tested with the Instant-View multitest, whereas the urine of patient C also tested positive for opiates. None of the patients or parents were receiving methylphenidate, tenocilidine, or pheniramine, drugs known to produce false-positive results for PCP in this multitest immunoassay, as reported by the manufacturer. Urine samples from these 3 patients that were screened by Instant-View multitest were subsequently analyzed by gas chromatography–mass spectrometry (GC-MS). A comprehensive systematic toxicological analysis was performed after basic, neutral, and acidic liquid–liquid extraction with use of full-scan GC-MS. All the samples were negative for PCP and for all the drugs-of-abuse classes covered by the immunoassay. Conversely, the presence of ibuprofen, metamizol, and dextromethorphan and their metabolites was detected in urine from patient A, patient B, and patient C, respectively. Indeed, upon interview, the mother of patient A declared that the boy had been administered several pediatric doses of ibuprofen syrup that day because of otalgia. From clinical records, it was discovered that the mother of patient B had been treated with metamizol during delivery. Finally, the mother of patient C acknowledged possible accidental ingestion of dextromethorphan by her baby, who had been left alone in the parents’ bathroom, where this medication was present. Ibuprofen is classified as a nonsteroidal anti-inflammatory drug (NSAID) and is used to reduce fever and treat pain or inflammation caused by many conditions. The drug is excreted in urine partly unmodified and partly as the metabolites. The 2 major metabolites, 2hydroxyibuprofen and carboxyibuprofen, and their glucuronic acid conjugates in urine were found to account for approximately 58% of the given dose of ibuprofen, whereas the 2 minor metabolites, 1-hydroxyibuprofen and 3-hydroxyibuprofen, and their glucuronic acid conjugates were found to be present in only very small concentrations. International literature relates that ibuprofen is known to cause false-positive results with several PCP immunoassays, but there is no such reference with respect to Instant-View, the immunoassay used in the emergency department in Hospital del Mar. Metamizol sodium, an NSAID of the pyrazolone group, is widely used and has effective analgesic, antipyretic, and antispasmodic properties.After oral or intravenous administration, unchanged metamizol is almost undetectable in urine, because it is rapidly hydrolyzed to the active moiety 4-methylaminoantipyrine. This latter metabolite is further metabolized to 4-formylaminoantipyrine (FAA) and 4-aminoantipyrine (AA), which is acetylated to 4-acetylaminoantipyrine. Dextromethorphan is an antitussive drug that is found in many over-thecounter cold and cough preparations, usually in the form of dextromethorphan hydrobromide. It is also commonly used at high doses as a recreational drug. In fact, acute megadoses of the drug have profound psychological and physiological effects similar to those of PCP. Dextromethorphan is structurally related to levorphanol, a narcotic (opioid) analgesic, but differences in their stereochemistry account for why levorphanol is a potent opioid analgesic whereas dextromethorphan interacts with opioid receptors only in overdose situations. Dextromethorphan is known to be metabolized by both Oand N-demethylation to dextrorphan, an active metabolite, and to 3-methoxymorphinan and 3-hydroxymorphinan. It is primarily excreted as unchanged parent drug and dextrorphan. It has been reported that megadoses of dextromethorphan used to self-intoxicate can cause false-positivity in screenings for phencyclidine in urine specimens, apart from correct positive results in screenings for opiates.