B-315 Unexpectedly High Amphetamine Concentrations in a Liver Transplant Candidate: A Case of Vyvanse (Lisdexamfetamine) Interference in Urine Drug Testing

Background Urine drug screening (UDS) is critical for the rapid identification of drugs of abuse; however, it is essential to confirm preliminary positive results using mass spectrometry due to the susceptibility of immunoassay-based UDS to false positives. Although confirmatory testing is considered definitive, discrepancies can arise when patients adamantly deny illicit drug use despite confirmed positive results, leading to confusion and challenges for the medical team. Additionally, patients may already be on various medications and have hepatic dysfunctions that can contribute to altered drug metabolism and excretion, resulting in unexpected drug concentrations. For transplant candidates, abnormal toxicology screening results can impact eligibility, underscoring the importance of accurate interpretation of UDS results. We present a case involving unexpected positive amphetamine immunoassay results that were confirmed by mass spectrometry. Methods A 48-year-old male with a history of alcohol-related cirrhosis, hyperlipidemia, and hypogonadism was undergoing liver transplant evaluation after ceasing alcohol use since July 2024. His social history included past cigarette smoking and routine marijuana use four times per week. As part of his pre-transplant workup, a routine immunoassay urine drug screen was performed using the Roche Cobas immunoassay analyzer which tests for: barbiturates, benzodiazepines, cannabinoids, cocaine, ethanol, fentanyl, hydrocodone, methadone, methamphetamine/amphetamines, opiates, and oxycodone. Confirmatory LC-MS/MS testing was performed at a reference send out laboratory. In addition, to investigate potential analytical interference, such as cross-reactivity and metabolic effects of hepatic dysfunction, a literature review was conducted. Results The patient*s urine screened positive for amphetamines and cannabinoids by immunoassay, while negative for alcohol and the other analytes on the immunoassay UDS panel. The patient denied illicit amphetamine use but reported prescribed Vyvanse for attention deficit disorder. Given the implications for transplant eligibility, confirmatory LC-MS/MS testing was ordered on the positive immunoassay drug screen results. Confirmatory testing performed by ARUP reference laboratory using LC-MS/MS methodology revealed an amphetamine concentration of >5000 ng/mL (negative for methamphetamine, MDA, MDMA, MDEA and Pentamine) and a THC metabolite (11-Nor-9-carboxy-THC) of >500 ng/mL. Given that the patient was adamant on denying use of drugs, the supratherapeutic amphetamine concentration raised concerns and plausible scenarios were considered to explain the unexpected results: 1) Immunoassays for amphetamines lacking specificity, increasing the risk of false-positive interpretations 2) amphetamine was directly added to the urine 3) the urine sample was adulterated by adding chemicals that interfere with the immunoassay detection 4) medical chart review conducted to identify if possible medications can explain the results. Conclusion This case highlights the challenges of interpreting urine drug screening results in patients with hepatic dysfunction and those undergoing organ transplantation evaluations. While LC-MS/MS confirmatory testing is considered the gold standard, Vyvanse (lisdexamfetamine) is a prodrug that gets converted to dextroamphetamine. This case suggests that lisdexamfetamine metabolism in liver disease may yield abnormally high amphetamine concentrations. Thorough medical chart reviews and understanding analytical interferences and pharmacokinetic variations is essential to prevent unnecessary transplant disqualifications and ensure accurate toxicology assessments. Further studies are needed to optimize drug testing methodologies and develop guidelines for amphetamine interpretation in medically complex patients.