Research Article: A validated workflow for drug detection in oral fluid by non-targeted liquid chromatography-tandem mass spectrometry

Date Published: December 6, 2018

Publisher: Springer Berlin Heidelberg

Author(s): Vera Reinstadler, Stefan Lierheimer, Michael Boettcher, Herbert Oberacher.

http://doi.org/10.1007/s00216-018-1504-x

Abstract

Oral fluid is recognized as an important specimen for drug testing. Common applications are monitoring in substance abuse treatment programs, therapeutic drug monitoring, pain management, workplace drug testing, clinical toxicology, and driving under the influence of drugs (DRUID). In this study, we demonstrate that non-targeted LC-MS/MS with subsequent compound identification by tandem mass spectral library search is a valuable tool for comprehensive detection and confirmation of drugs in oral fluid samples. The workflow developed involves solid-phase extraction and chromatographic separation on reversed phase materials. Mass spectrometric detection is accomplished on a quadrupole–quadrupole-time-of-flight instrument operated with data-dependent acquisition control. The workflow was optimized for 500 μl of neat oral fluid collected with the Greiner Bio-One saliva collection system. The fitness of the developed method was tested and proven by analyzing blank and spiked samples as well as 59 authentic patient samples. We could demonstrate that compounds with logP values in the range 0.5–5.5 are efficiently detected at low nanograms per milliliter concentrations. The true positive and true negative rates of automated library search were equal or close to 100%. The beauty of the non-targeted LC-MS/MS approach is the ability to detect compounds hardly included in routinely applied targeted assays, and this was demonstrated by detecting the synthetic opioid U-47700 in two patient samples.

Partial Text

Oral fluid is recognized as an important specimen for drug testing [1]. Common applications are monitoring in substance abuse treatment programs, therapeutic drug monitoring, pain management, workplace drug testing, clinical toxicology, and driving under the influence of drugs (DRUID). Oral fluid can be used to confirm the recent consume of all major types of abused drugs [2–4]. Even new psychoactive substances (NPS) are detectable [5–8]. Furthermore, the monitoring of legally prescribed drugs such as benzodiazepines, z-hypnotics, methadone, and buprenorphine is common [9–11].

Non-targeted LC-MS/MS with DDA represent a valuable tool for comprehensive drug screening in oral fluid samples. By combining this technique with solid-phase extraction, LOI in the low nanograms per milliliter range are achieved. Accordingly, for all common drug compounds, the detection capabilities are sufficient to meet the requirements issued in the context of monitoring in substance abuse treatment programs, workplace drug testing, and DRUID. Targeted data mining involving tandem mass spectral library search enables reliable compound identification. Automated library search produced no false negative result and only a low number of false positive results (< 2%). However, the false positives are acceptable as they are sorted out by expert reviewing.   Source: http://doi.org/10.1007/s00216-018-1504-x

 

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