TY - JOUR
T1 - An ultra-rapid drug screening method for acetaminophen in blood serum based on probe electrospray ionization-tandem mass spectrometry
AU - Usui, Kiyotaka
AU - Kobayashi, Haruka
AU - Fujita, Yuji
AU - Kubota, Eito
AU - Hanazawa, Tomoki
AU - Yoshizawa, Tomohiro
AU - Kamijo, Yoshito
AU - Funayama, Masato
N1 - Funding Information:
This study was partly funded by Shimadzu Corporation .
Funding Information:
This work was supported in part by Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (B) 16H05495 . We would like to thank Tasuku Murata (Shimadzu Corporation) for his helpful advice regarding data acquisition.
Publisher Copyright:
© 2019
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - Acetaminophen
KW - Blood serum
KW - Probe electrospray ionization
KW - Rapid drug screening
KW - Tandem mass spectrometry
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U2 - 10.1016/j.jfda.2019.02.001
DO - 10.1016/j.jfda.2019.02.001
M3 - Article
C2 - 31324294
AN - SCOPUS:85062058249
SN - 1021-9498
VL - 27
SP - 786
EP - 792
JO - Journal of Food and Drug Analysis
JF - Journal of Food and Drug Analysis
IS - 3
ER -
