A Comprehensive Approach to Targeted and Untargeted Screening Methodology for Emerging Synthetic Fentanyl Analogues using High Resolution Accurate Mass Spectrometry

In a rapidly changing environment with new synthetic drugs appearing almost weekly, there is an analytical need to confidently identify these analytes in a timely manner.  The use of high-resolution accurate mass technology coupled with a novel sample preparation using Agilent’s Captiva EMR-Lipid allows for highly specific, selective and comprehensive screening for the identification of these emerging fentanyl analogues in serum matrix. Captiva EMR–Lipid provides highly selective and efficient lipid/matrix removal without unwanted analyte loss. The novel EMR-Lipid technology removes lipids based on a combination of size exclusion and hydrophobic interaction. Effective lipid removal assures minimal ion suppression of target analytes, which significantly improves method reliability and ruggedness.  This novel sample preparation approach allows for lower limits of detection and quantitation as well as better linearity across the entire dynamic range. 

Immunoassay-based techniques have historically been the methods of choice for drug screening. Positive presumptive drug screen results are reflexed to more specific, confirmatory testing using gas or liquid chromatography coupled to mass spectrometry. False positives and false negatives with immunoassay techniques are common problems that have substantial down-stream consequences for inaccurate results, laboratory operations, and total costs.  Thus, the use of high-resolution accurate mass liquid chromatography mass spectrometry (LC-QTOF-MS) is ideally suited for rapid analysis of emerging drugs without the drawbacks associated with legacy techniques and methodology.  Herein, a targeted and untargeted screening workflow by LC/MS/MS using Agilent’s 6546 QTOF will be presented for approximately 150 fentanyl analogues.
 
For Forensic Use.