Skip to main content
Top
Published in: Forensic Toxicology 2/2021

01-07-2021 | Diphenhydramine | 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

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

Published in: Forensic Toxicology | Issue 2/2021

Login to get access

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.
Literature
5.
6.
go back to reference 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.
go back to reference 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.
go back to reference 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
15.
go back to reference 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.
go back to reference 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
Metadata
Title
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
Authors
Keiko Kudo
Kanju Saka
Brian Waters
Kenji Hara
Aya Matsusue
Masayuki Kashiwagi
Shin-ichi Kubo
Publication date
01-07-2021
Publisher
Springer Singapore
Published in
Forensic Toxicology / Issue 2/2021
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-021-00580-z

Other articles of this Issue 2/2021

Forensic Toxicology 2/2021 Go to the issue