B-309 Validation and Application of a Gas Chromatography–Mass Spectrometry Method in Emergency Drug Testing

Abstract Background Qualitative urine drug screening is important in identifying or ruling out the presence of toxic substances in suspected overdose cases. However, high-throughput immunoassay panels cover only a limited range of drug classes. When clinical symptoms do not align with immunoassay results, mass spectrometry-based confirmatory tests are ordered. As a robust, reliable, and cost-effective instrument, GC-MS has been used in toxicology laboratories since the 1980s. Recently, we transferred and validated our in-house GC-MS drug test to a new instrument installed with the NIST 23 library. Two case studies involving sertraline and xylazine demonstrated its clinical utilities in STAT drug testing. Methods Our in-house immunoassay panel includes amphetamines/methamphetamines, benzodiazepines, cocaine, opiates, and cannabinoids. To expand the drug screening list, a qualitative GC-MS drug screen was validated on an 8860 GC system with a 5977C MSD (Agilent). Unknown and quality control urine samples were spiked with four internal standards (Table 1). Liquid-liquid extractions were performed in acidic and basic conditions. Organic fractions were dried, reconstituted, and combined before analysis. We determined the limit of detection for thirty compounds in spiked urine specimens (3 mL). Method comparison was performed by sending twenty specimens to a reference laboratory. We expanded the test menu to include about 100 medications and illicit drugs. Results Because this project is considered a method transfer to replace an outdated equipment, no changes was made to the analytical method. Precision was assessed by analyzing positive QC samples in triplicate for six days. Split samples comparison was performed to evaluate the method accuracy. GC-MS results were compared to a sensitive LC-MS/MS drug panel to assess its limitations. Application of GC-MS drug screen was demonstrated in two case studies. Case 1. A female patient was brought to the emergency department (ED) due to suicidal ideation and multiple-drug overdose. Immunoassay screen was positive for benzodiazepines. GC-MS urine drug test was positive for midazolam, citalopram, gabapentin, sertraline, ibuprofen, and methocarbamol. Medical record showed that midazolam was administered in the hospital to prevent seizure. Patient admitted taking other five medications, which were revealed by the GC-MS drug screen. Case 2. A female patient presented to the ED with bilateral knee wounds. Immunoassays were positive for cocaine metabolite and opiates. GC-MS drug screen identified xylazine, ibuprofen, and lidocaine in serum specimen. Patient endorsed fentanyl, cocaine, and heroin use. Xylazine was commonly seen in illicitly manufactured fentanyl as an adulterant. Chronic exposure to xylazine lead to delayed wound healing. Again, GC-MS drug screen identified the agent responsible for skin ulcer. Conclusion We validated a confirmatory drug test on a new GC-MS instrument. Validation report meets the requirement of current regulatory standards. Two case studies demonstrated the value of broad-spectrum GC-MS drug screen in supporting clinical teams of the emergency department