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Erschienen in: Forensic Toxicology 2/2021

11.05.2021 | Original Article

Effects of putrefaction on the quantitative analyses of diphenhydramine in blood and tissues: model experiments by the routine matrix-matched calibration method and standard addition method with different internal standards

verfasst von: Keiko Kudo, Kanju Saka, Brian Waters, Kenji Hara, Aya Matsusue, Masayuki Kashiwagi, Shin-ichi Kubo

Erschienen in: Forensic Toxicology | Ausgabe 2/2021

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Abstract

Purpose

The purpose of this study was to elucidate the effect of putrefaction on the quantitative analyses of diphenhydramine in blood and tissues by the routine matrix-matched calibration (MMC) method and the standard addition (SA) method for comparison.

Methods

Putrefied samples were prepared by leaving pig blood, liver and muscle at room temperature. Toxic amounts of diphenhydramine and six internal standards (ISs) having different similarities were added to the prepared samples, and the drug was extracted with a liquid-liquid extraction method. The concentrations of diphenhydramine were determined by liquid chromatography–tandem mass spectrometry. The accuracies and precisions of the obtained quantitative values were compared in each quantification method. The results were also verified using human blood and tissues obtained at the time of autopsy.

Results

In the MMC method, the deuterium-labeled IS showed good accuracies and precisions for putrefied samples. On the other hand, the concentrations of diphenhydramine using some non-isotopic ISs were found to deviate significantly from the true value.

Conclusions

The obtained results showed that the MMC method using fresh blood calibration curve with isotope-labeled IS could accurately measure drug concentrations in putrefied blood and tissues. If the isotope-labeled compound is not available, the quantification by the MMC method seems effective using several ISs with high similarity. This kind of study on the effects of putrefaction on forensic analyses has not been reported to our knowledge.
Literatur
5.
Zurück zum Zitat Hewavitharana AK, Abu Kassim NS, Shaw PN (2018) Standard addition with internal standardization as an alternative to using stable isotope labelled internal standards to correct for matrix effects- Comparison and validation using liquid chromatography-tandem mass spectrometric assay of vitamin D. J Chromatogr A 1553:101–107. https://doi.org/10.1016/j.chroma.2018.04.026CrossRefPubMed Hewavitharana AK, Abu Kassim NS, Shaw PN (2018) Standard addition with internal standardization as an alternative to using stable isotope labelled internal standards to correct for matrix effects- Comparison and validation using liquid chromatography-tandem mass spectrometric assay of vitamin D. J Chromatogr A 1553:101–107. https://​doi.​org/​10.​1016/​j.​chroma.​2018.​04.​026CrossRefPubMed
6.
Zurück zum Zitat Gergov M, Nenonen T, Ojanperä I, Ketola RA (2015) Compensation of matrix Effects in a standard addition method for metformin in postmortem blood using liquid chromatography–electrospray-tandem mass spectrometry. J Anal Toxicol 39:359–364. https://doi.org/10.1093/jat/bkv020 (open access article) Gergov M, Nenonen T, Ojanperä I, Ketola RA (2015) Compensation of matrix Effects in a standard addition method for metformin in postmortem blood using liquid chromatography–electrospray-tandem mass spectrometry. J Anal Toxicol 39:359–364. https://​doi.​org/​10.​1093/​jat/​bkv020 (open access article)
9.
Zurück zum Zitat Hasegawa K, Wurita A, Nozawa H, Yamagishi I, Minakata K, Watanabe K, Suzuki O (2018) Fatal zolpidem poisoning due to its intravenous self-injection: Postmortem distribution/redistribution of zolpidem and its predominant metabolite zolpidem phenyl-4-carboxylic acid in body fluids and solid tissues in an autopsy case. Forensic Sci Int 290:111–120. https://doi.org/10.1016/j.forsciint.2018.06.044CrossRef Hasegawa K, Wurita A, Nozawa H, Yamagishi I, Minakata K, Watanabe K, Suzuki O (2018) Fatal zolpidem poisoning due to its intravenous self-injection: Postmortem distribution/redistribution of zolpidem and its predominant metabolite zolpidem phenyl-4-carboxylic acid in body fluids and solid tissues in an autopsy case. Forensic Sci Int 290:111–120. https://​doi.​org/​10.​1016/​j.​forsciint.​2018.​06.​044CrossRef
13.
Zurück zum Zitat Kudo K, Ishida T, Hikiji W, Hayashida M, Uekusa K, Usumoto Y, Tsuji A, Ikeda N (2009) Construction of calibration-locking databases for rapid and reliable drug screening by gas chromatography–mass spectrometry. Forensic Toxicol 27:21- 31. https://doi.org/10.1007/s11419-009-0066-1 Kudo K, Ishida T, Hikiji W, Hayashida M, Uekusa K, Usumoto Y, Tsuji A, Ikeda N (2009) Construction of calibration-locking databases for rapid and reliable drug screening by gas chromatography–mass spectrometry. Forensic Toxicol 27:21- 31. https://​doi.​org/​10.​1007/​s11419-009-0066-1
14.
15.
Zurück zum Zitat Anastassiades M, Lehotay SJ, Stajnbaher D, Schenck FJ (2003) Fast and easy multiresidue method employing acetonitrile extraction/partitioning and “dispersive solid-phase extraction” for the determination of pesticide residues in produce. J AOAC Int 86:412–431. https://doi.org/10.1093/jaoac/86.2.412 (open access article)CrossRef Anastassiades M, Lehotay SJ, Stajnbaher D, Schenck FJ (2003) Fast and easy multiresidue method employing acetonitrile extraction/partitioning and “dispersive solid-phase extraction” for the determination of pesticide residues in produce. J AOAC Int 86:412–431. https://​doi.​org/​10.​1093/​jaoac/​86.​2.​412 (open access article)CrossRef
18.
Zurück zum Zitat Baselt RC (2017) Disposition of toxic drugs and chemicals in man, 11th edn. Biomedical Publications, Seal Beach, CA, pp 716–718 Baselt RC (2017) Disposition of toxic drugs and chemicals in man, 11th edn. Biomedical Publications, Seal Beach, CA, pp 716–718
Metadaten
Titel
Effects of putrefaction on the quantitative analyses of diphenhydramine in blood and tissues: model experiments by the routine matrix-matched calibration method and standard addition method with different internal standards
verfasst von
Keiko Kudo
Kanju Saka
Brian Waters
Kenji Hara
Aya Matsusue
Masayuki Kashiwagi
Shin-ichi Kubo
Publikationsdatum
11.05.2021
Verlag
Springer Singapore
Erschienen in
Forensic Toxicology / Ausgabe 2/2021
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-021-00580-z

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