Rethinking Drug Analysis in Health Care: High-Throughput Analysis of 71 Drugs of Abuse in Oral Fluid Using Ion Mobility--High-Resolution Mass Spectrometry

Abstract

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 practice 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 the analysis of drugs of abuse (DoA) in oral fluid (OF). The method covers a panel of 71 substances including traditional 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 sample preparation 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. Seventy-one percent 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. New psychoactive substances were detected in 189 samples (1.0%). The 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 LC-HRMS and the largest dataset published on the 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.

Retrospective identification of new psychoactive substances in patient samples submitted for clinical drug analysis

“…Reference materials were purchased from Cayman Chemical, LGC Standards, Cerilliant Corporation or obtained from the Swedish National Forensic Centre (NFC). Other chemicals were obtained from previously described sources 28 …”

“…Samples were stored at 4°C before analysis and were analysed within 1–3 days after arrival to the laboratory. Sample pre‐treatment before LC‐HRMS analysis was carried out as previously described 28 …”

“…Oral fluid samples were analysed by LC‐HRMS on Waters Acquity I‐class UPLC systems coupled to Vion ion mobility spectrometry (IMS)‐quadrupole time‐of‐flight mass spectrometers (Waters Corporation) equipped with an electrospray ionization interface. The analysis was carried out as previously described but with a slight modification 28 . The modification consisted of different time points for the chromatographic gradient that was used for samples collected between January–April 2019 (supporting information Table S1 and Figure S1).…”

“…The Waters UNIFI software v 1.9.4 was used for data acquisition and the accurate mass screening of IMS data workflow in the Waters UNIFI for data processing. Quality control samples at two levels containing all analytes included in the routine analysis were included in each analytical batch, as previously described 28 …”

Oral fluid analysis to monitor recent exposure to synthetic cannabinoids in a high‐risk subpopulation

“…It proved useful to demonstrate recent exposure when it came to driving issues [14,15] and workplace drug testing [16,17]. Oral fluid was demonstrated to be a valuable matrix also for detecting specifically NPS [18,19]. In particular, synthetic cannabinoids have been detected in oral fluid samples of students [20], drivers [21], administration-controlled studies, [22] and homeless population [10].…”