Rethinking Drug Analysis in Healthcare: High-Throughput Analysis of 71 Drugs of Abuse in Oral Fluid using Ion Mobility - High Resolution Mass Spectrometry.

We have identified a clinical need for a sensitive, specific, flexible, comprehensive, and affordable analytical technology to efficiently detect polydrug use. In addition, the current standard practise of surveilled urine sampling is uncomfortable for the patient, hence more patient-friendly sample collection methods are requested. To fill these needs, we have developed and validated a high-throughput liquid chromatography - high resolution mass spectrometry (LC-HRMS) method for analysis of DoA in oral fluid (OF). The method covers a panel of 71 substances including traditional drugs of abuse (DoA), prescription narcotics and new psychoactive substances (NPS), with a guaranteed limit of identification of <3 µg/L for 87% of the analytes. Method validation showed high accuracy (>99.7%), sensitivity (>99.7%) and specificity (100%). Most analytes had a high process efficiency during the salting out liquid-liquid extraction (SALLE) workup and no or only a minor matrix effect during the analysis. We have implemented this method in clinical routine, and present data from 18,579 OF samples collected during routine patient treatment in mainly psychiatric and addiction clinics in West Sweden between September 2020 and June 2021. 71% of the samples were positive and a total of 41,472 DoA findings were detected. Amphetamine (27%), buprenorphine (25%), nordiazepam (18%) and alprazolam (16%) were most prevalent. NPS were detected in 189 samples (1.0%). Occurrence of polydrug use was common, 34% of the positive samples contained three analytes or more and 12% six or more. To the best of our knowledge, this is the first method for comprehensive analysis of DoA in OF using HRMS and the largest dataset published on detection of DoA in OF. With the current complex and variable drug use pattern, this broad, cost-effective and reliable method has largely replaced immunoassay screening in urine in our laboratory.