An ultra-rapid drug screening method for acetaminophen in blood serum based on probe electrospray ionization-tandem mass spectrometry

Kiyotaka Usui, Haruka Kobayashi, Yuji Fujita, Eito Kubota, Tomoki Hanazawa, Tomohiro Yoshizawa, Yoshito Kamijo, Masato Funayama

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Poisoning incidents caused by drugs, accidental ingestion of poisons, attempted suicide, homicide, and exposure to toxic compounds occur frequently every year across the globe. This raises the need to rapidly identify toxic agents in poisoned patients in a clinical emergency setting. In addition, determining drug/poison concentration is undoubtedly necessary to arrive at a toxicological treatment plan. The purpose of this study was to develop an ultra-rapid drug screening method for the clinical treatment of poisoning. Probe electrospray ionization (PESI), one of the ambient ionization techniques, is able to detect compounds from various biological materials almost directly. We applied the PESI technique to the rapid detection of acetaminophen (APAP). Blood serum samples were diluted 100-fold with 10 mM ammonium formate/ethanol (1:1 v/v) solution including deuterium-labeled internal standards (IS; APAP-d4). Only 10 μL of the diluted sample was used for measurement. The tandem mass spectrometer (MS/MS) equipped with a PESI was used in selected reaction monitoring mode for the quantitation of APAP; the measurement time was only 18 s. Transitions were set at 152 > 110 for quantitation, 152 > 65 for qualifier, and 156 > 114 for IS (APAP-d4). All measurements were conducted in positive mode. The calibration curve (1/x2) was linear over the range of 1.56–200 μg/mL (r2 = 0.998), and the limit of detection and quantitation were 0.37 μg/mL and 1.56 μg/mL, respectively. The accuracy (bias) and precision (RSD%) of the method were within an acceptable range (−0.15–2.8% and 2.3–6.1%, respectively) and matrix effect at 3 concentrations (95.1–104%) indicated that PESI-MS/MS is only slightly affected by matrices. In real forensic cases, quantitative values of APAP determined by the PESI-MS/MS were almost identical to those determined by the liquid chromatography-MS/MS method. Since PESI-MS/MS is a simple, reliable, and rapid determination method for toxic agents with virtually no need for blood serum pre-treatment, it would be highly suitable for poisoning cases in clinical emergency settings. In the future, a method for simultaneous rapid determination of multiple toxic agents will be developed.

Original languageEnglish
Pages (from-to)786-792
Number of pages7
JournalJournal of Food and Drug Analysis
Volume27
Issue number3
DOIs
Publication statusPublished - 2019 Jul
Externally publishedYes

Keywords

  • Acetaminophen
  • Blood serum
  • Probe electrospray ionization
  • Rapid drug screening
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

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