Abstract

Acoustic ejection mass spectrometry is a novel high-throughput analytical technology that delivers high reproducibility without carryover observed. It eliminates the chromatography step used to separate analytes from matrix components. Fully-automated liquid–liquid extraction is widely used for sample cleanup, especially in high-throughput applications. We introduce a workflow for direct AEMS analysis from phase-separated liquid samples and explore high-throughput analysis from complex matrices. We demonstrate the quantitative determination of fentanyl from urine using this two-phase AEMS approach, with a LOD lower than 1 ng/mL, quantitation precision of 15%, and accuracy better than ±10% over the range of evaluation (1–100 ng/mL). This workflow offers simplified sample preparation and higher analytical throughput for some bioanalytical applications, in comparison to an LC-MS based approach.

Highlights

  • Mass spectrometry (MS) provides the high-sensitivity, high-fidelity, and high-specificity essential for various chemical and biological quantitation workflows, including drug discovery [1], forensic analysis [2], food safety [3], and environmental monitoring [4]

  • Dynamic fluid analysis (DFA) signal processing is complex and time consuming; as such, the algorithm can be optimized for speed, or for a wide range of fluid properties, but cannot manage both a high speed and a wide range of fluid properties

  • We further evaluated a variety of in-well liquid–liquid extraction (LLE) conditions, including five different aqueous matrices

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Summary

Introduction

Mass spectrometry (MS) provides the high-sensitivity, high-fidelity, and high-specificity essential for various chemical and biological quantitation workflows, including drug discovery [1], forensic analysis [2], food safety [3], and environmental monitoring [4]. MS has made tremendous strides, there remain challenges, including high-throughput sample introduction and time-consuming sample preparation. Liquid chromatography (LC) is employed as the primary sample introduction method. There is a throughput mismatch with MS that limits its practical use in high-throughput applications. Typical LC sample times are greater than 10 s, while MS sample times are measured in ms [5]. Complex samples require a time and labor-intensive sample clean-up with LC-MS, to reduce ionization suppression and improve system robustness

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