Forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases
Abstract A gas chromatography-mass spectrometry (GC–MS) method for the determination of difenidol hydrochloride in biological specimens has been developed. The method exhibited excellent recovery (> 90%) and precision (RSD < 10%), and the LOD was 0.05 μg/mL or μg/g, which met the requirements...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38246-y |
| _version_ | 1797778924426493952 |
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| author | Weifen Niu Tongxi Ren Yandan Wang Zheyu Wang Chao Zhang Juan Jia Zhiwen Wei Hongliang Su Zhongyuan Guo Xiangjie Guo Keming Yun |
| author_facet | Weifen Niu Tongxi Ren Yandan Wang Zheyu Wang Chao Zhang Juan Jia Zhiwen Wei Hongliang Su Zhongyuan Guo Xiangjie Guo Keming Yun |
| author_sort | Weifen Niu |
| collection | DOAJ |
| description | Abstract A gas chromatography-mass spectrometry (GC–MS) method for the determination of difenidol hydrochloride in biological specimens has been developed. The method exhibited excellent recovery (> 90%) and precision (RSD < 10%), and the LOD was 0.05 μg/mL or μg/g, which met the requirements of bioanalytical method. Through the animal model of the forensic toxicokinetics, the dynamic distribution, postmortem redistribution (PMR) and stability in specimen preservation process of difenidol in animals were studied. The experimental results showed that after intragastric administration, the difenidol’s concentrations in the heart-blood and various organs increased over time except stomach, and then decreased gradually after reaching the peaks of concentration. The toxicological kinetics equation and toxicokinetic parameters were established by processing the data of the mean drug concentration of difenidol changing with time. In PMR experiment, the concentrations of difenidol in some organs closer to the gastrointestinal tract (heart-blood, heart, liver, lung, kidney, and spleen) changed significantly at different time points. But the concentration of difenidol in brain tissues which were far away from the gastrointestinal tract and muscles with larger overall mass was relatively stable. PMR of difenidol was therefore confirmed. Thus, the effect of PMR on the concentration of difenidol in the specimens should be considered in cases involving difenidol poisoning or death. Furthermore, the stability of difenidol in heart-blood samples from poisoned rats was investigated at various time points and under different preservation conditions (20 °C, 4 °C, − 20 °C and 20 °C (1% NaF)) for a period of two months. Difenidol was stable and did not decompose in the preserved blood. Therefore, this study provided the experimental basis for the forensic identification of the cases of difenidol hydrochloride poisoning (death). PMR has been verified by practical lethal cases. |
| first_indexed | 2024-03-12T23:23:33Z |
| format | Article |
| id | doaj.art-b4030e75439544b9a59284c2cd515518 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T23:23:33Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b4030e75439544b9a59284c2cd5155182023-07-16T11:17:01ZengNature PortfolioScientific Reports2045-23222023-07-011311710.1038/s41598-023-38246-yForensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal casesWeifen Niu0Tongxi Ren1Yandan Wang2Zheyu Wang3Chao Zhang4Juan Jia5Zhiwen Wei6Hongliang Su7Zhongyuan Guo8Xiangjie Guo9Keming Yun10School of Forensic Medicine, Shanxi Medical UniversityInstitute of Forensic Science of Tianjin Public Security BureauSchool of Forensic Medicine, Shanxi Medical UniversitySchool of Forensic Medicine, Shanxi Medical UniversitySchool of Forensic Medicine, Shanxi Medical UniversitySchool of Forensic Medicine, Shanxi Medical UniversitySchool of Forensic Medicine, Shanxi Medical UniversitySchool of Forensic Medicine, Shanxi Medical UniversitySchool of Forensic Medicine, Shanxi Medical UniversitySchool of Forensic Medicine, Shanxi Medical UniversitySchool of Forensic Medicine, Shanxi Medical UniversityAbstract A gas chromatography-mass spectrometry (GC–MS) method for the determination of difenidol hydrochloride in biological specimens has been developed. The method exhibited excellent recovery (> 90%) and precision (RSD < 10%), and the LOD was 0.05 μg/mL or μg/g, which met the requirements of bioanalytical method. Through the animal model of the forensic toxicokinetics, the dynamic distribution, postmortem redistribution (PMR) and stability in specimen preservation process of difenidol in animals were studied. The experimental results showed that after intragastric administration, the difenidol’s concentrations in the heart-blood and various organs increased over time except stomach, and then decreased gradually after reaching the peaks of concentration. The toxicological kinetics equation and toxicokinetic parameters were established by processing the data of the mean drug concentration of difenidol changing with time. In PMR experiment, the concentrations of difenidol in some organs closer to the gastrointestinal tract (heart-blood, heart, liver, lung, kidney, and spleen) changed significantly at different time points. But the concentration of difenidol in brain tissues which were far away from the gastrointestinal tract and muscles with larger overall mass was relatively stable. PMR of difenidol was therefore confirmed. Thus, the effect of PMR on the concentration of difenidol in the specimens should be considered in cases involving difenidol poisoning or death. Furthermore, the stability of difenidol in heart-blood samples from poisoned rats was investigated at various time points and under different preservation conditions (20 °C, 4 °C, − 20 °C and 20 °C (1% NaF)) for a period of two months. Difenidol was stable and did not decompose in the preserved blood. Therefore, this study provided the experimental basis for the forensic identification of the cases of difenidol hydrochloride poisoning (death). PMR has been verified by practical lethal cases.https://doi.org/10.1038/s41598-023-38246-y |
| spellingShingle | Weifen Niu Tongxi Ren Yandan Wang Zheyu Wang Chao Zhang Juan Jia Zhiwen Wei Hongliang Su Zhongyuan Guo Xiangjie Guo Keming Yun Forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases Scientific Reports |
| title | Forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases |
| title_full | Forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases |
| title_fullStr | Forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases |
| title_full_unstemmed | Forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases |
| title_short | Forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases |
| title_sort | forensic toxicokinetics of difenidol hydrochloride in vivo verified by practical lethal cases |
| url | https://doi.org/10.1038/s41598-023-38246-y |
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