Stability of ten psychotropic drugs in formalin-fixed porcine liver homogenates
•Porcine liver homogenates (PLHs) added with psychotropic drugs were formalin-fixed.•Drug concentrations after formalin fixation were analyzed periodically for 6 months.•Residual ratios of all drugs except for estazolam were >10 % after 4 weeks.•Residual ratios of 5 out of 10 drugs were >25 %...
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| Veröffentlicht in: | Forensic science international 2020-02, Vol.307, p.110136, Article 110136 |
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| creator | Asano, Migiwa Yoshioka, Naoki Kuse, Azumi Kuwahara, Natsumi Nakabayashi, Yuki Takahashi, Motonori Kondo, Takeshi Morichika, Mai Nakagawa, Kanako Sakurada, Makoto Ueno, Yasuhiro |
| description | •Porcine liver homogenates (PLHs) added with psychotropic drugs were formalin-fixed.•Drug concentrations after formalin fixation were analyzed periodically for 6 months.•Residual ratios of all drugs except for estazolam were >10 % after 4 weeks.•Residual ratios of 5 out of 10 drugs were >25 % even after 6 months.•Formalin-fixed PLHs could be useful samples in forensic toxicology.
In forensic toxicology studies, drug concentrations must be estimated by the analytical data of formalin-fixed tissues if fresh or frozen tissue specimens are not available. We wished to investigate the stability and time-course of metabolism/degradation of drugs in formalin-fixed tissues using porcine liver homogenates (PLHs) instead of human tissue. Ten psychotropic drugs (amitriptyline, brotizolam, diazepam, diphenhydramine, estazolam, etizolam, levomepromazine, paroxetine, quetiapine and triazolam) were added to PLHs. After the PLHs had been fixed with neutral buffered formalin at room temperature, the concentrations of the drugs in the PLHs were determined by liquid chromatography–tandem mass spectrometry after 3 days, 1 week, 2 weeks, 4 weeks, 2 months, 4 months and 6 months. After 6 months, the residual ratio of amitriptyline, diphenhydramine and quetiapine was 80 %–95 %; that of diazepam, paroxetine and triazolam was 10 %–45 %; and that of brotizolam, etizolam and levomepromazine was 1 %–5 %. Estazolam was not detected from the first day of formalin fixation. These data suggest that the concentrations of drugs in PLHs measured after formalin fixation decreased to varying degrees compared with their initial concentrations. These time-dependent changes in drug concentration were due to degradation during preservation in formalin solution and metabolism by hepatic microsomal enzymes. |
| doi_str_mv | 10.1016/j.forsciint.2019.110136 |
| format | Article |
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In forensic toxicology studies, drug concentrations must be estimated by the analytical data of formalin-fixed tissues if fresh or frozen tissue specimens are not available. We wished to investigate the stability and time-course of metabolism/degradation of drugs in formalin-fixed tissues using porcine liver homogenates (PLHs) instead of human tissue. Ten psychotropic drugs (amitriptyline, brotizolam, diazepam, diphenhydramine, estazolam, etizolam, levomepromazine, paroxetine, quetiapine and triazolam) were added to PLHs. After the PLHs had been fixed with neutral buffered formalin at room temperature, the concentrations of the drugs in the PLHs were determined by liquid chromatography–tandem mass spectrometry after 3 days, 1 week, 2 weeks, 4 weeks, 2 months, 4 months and 6 months. After 6 months, the residual ratio of amitriptyline, diphenhydramine and quetiapine was 80 %–95 %; that of diazepam, paroxetine and triazolam was 10 %–45 %; and that of brotizolam, etizolam and levomepromazine was 1 %–5 %. Estazolam was not detected from the first day of formalin fixation. These data suggest that the concentrations of drugs in PLHs measured after formalin fixation decreased to varying degrees compared with their initial concentrations. These time-dependent changes in drug concentration were due to degradation during preservation in formalin solution and metabolism by hepatic microsomal enzymes.</description><identifier>ISSN: 0379-0738</identifier><identifier>EISSN: 1872-6283</identifier><identifier>DOI: 10.1016/j.forsciint.2019.110136</identifier><identifier>PMID: 31896021</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Amitriptyline ; Animals ; Benzodiazepines ; Chemicals ; Chromatography ; Chromatography, Liquid ; Degradation ; Diazepam ; Diphenhydramine ; Drug metabolism ; Drug Stability ; Drugs ; Fixation ; Fixatives ; Forensic science ; Forensic sciences ; Forensic toxicology ; Forensic Toxicology - methods ; Formaldehyde ; Formalin-fixed tissues ; Human tissues ; LC–MS/MS ; Liquid chromatography ; Liver ; Liver - chemistry ; Mass spectrometry ; Mass spectroscopy ; Microwaves ; Organ Preservation ; Paroxetine ; Preservation ; Psychotropic drugs ; Psychotropic Drugs - analysis ; Psychotropic Drugs - chemistry ; Quetiapine ; Room temperature ; Solvents ; Specimen Handling ; Stability ; Swine ; Tandem Mass Spectrometry ; Time dependence ; Tissues ; Toxicology ; Triazolam ; Vortices</subject><ispartof>Forensic science international, 2020-02, Vol.307, p.110136, Article 110136</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><rights>2019. Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-dbcc6eac8df7796fb981e646ed0687ed50cd2c047a3b74ab30532539c905accf3</citedby><cites>FETCH-LOGICAL-c465t-dbcc6eac8df7796fb981e646ed0687ed50cd2c047a3b74ab30532539c905accf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2344709184?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,64361,64365,65309,72215</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31896021$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asano, Migiwa</creatorcontrib><creatorcontrib>Yoshioka, Naoki</creatorcontrib><creatorcontrib>Kuse, Azumi</creatorcontrib><creatorcontrib>Kuwahara, Natsumi</creatorcontrib><creatorcontrib>Nakabayashi, Yuki</creatorcontrib><creatorcontrib>Takahashi, Motonori</creatorcontrib><creatorcontrib>Kondo, Takeshi</creatorcontrib><creatorcontrib>Morichika, Mai</creatorcontrib><creatorcontrib>Nakagawa, Kanako</creatorcontrib><creatorcontrib>Sakurada, Makoto</creatorcontrib><creatorcontrib>Ueno, Yasuhiro</creatorcontrib><title>Stability of ten psychotropic drugs in formalin-fixed porcine liver homogenates</title><title>Forensic science international</title><addtitle>Forensic Sci Int</addtitle><description>•Porcine liver homogenates (PLHs) added with psychotropic drugs were formalin-fixed.•Drug concentrations after formalin fixation were analyzed periodically for 6 months.•Residual ratios of all drugs except for estazolam were >10 % after 4 weeks.•Residual ratios of 5 out of 10 drugs were >25 % even after 6 months.•Formalin-fixed PLHs could be useful samples in forensic toxicology.
In forensic toxicology studies, drug concentrations must be estimated by the analytical data of formalin-fixed tissues if fresh or frozen tissue specimens are not available. We wished to investigate the stability and time-course of metabolism/degradation of drugs in formalin-fixed tissues using porcine liver homogenates (PLHs) instead of human tissue. Ten psychotropic drugs (amitriptyline, brotizolam, diazepam, diphenhydramine, estazolam, etizolam, levomepromazine, paroxetine, quetiapine and triazolam) were added to PLHs. After the PLHs had been fixed with neutral buffered formalin at room temperature, the concentrations of the drugs in the PLHs were determined by liquid chromatography–tandem mass spectrometry after 3 days, 1 week, 2 weeks, 4 weeks, 2 months, 4 months and 6 months. After 6 months, the residual ratio of amitriptyline, diphenhydramine and quetiapine was 80 %–95 %; that of diazepam, paroxetine and triazolam was 10 %–45 %; and that of brotizolam, etizolam and levomepromazine was 1 %–5 %. Estazolam was not detected from the first day of formalin fixation. These data suggest that the concentrations of drugs in PLHs measured after formalin fixation decreased to varying degrees compared with their initial concentrations. These time-dependent changes in drug concentration were due to degradation during preservation in formalin solution and metabolism by hepatic microsomal enzymes.</description><subject>Amitriptyline</subject><subject>Animals</subject><subject>Benzodiazepines</subject><subject>Chemicals</subject><subject>Chromatography</subject><subject>Chromatography, Liquid</subject><subject>Degradation</subject><subject>Diazepam</subject><subject>Diphenhydramine</subject><subject>Drug metabolism</subject><subject>Drug Stability</subject><subject>Drugs</subject><subject>Fixation</subject><subject>Fixatives</subject><subject>Forensic science</subject><subject>Forensic sciences</subject><subject>Forensic toxicology</subject><subject>Forensic Toxicology - methods</subject><subject>Formaldehyde</subject><subject>Formalin-fixed tissues</subject><subject>Human tissues</subject><subject>LC–MS/MS</subject><subject>Liquid chromatography</subject><subject>Liver</subject><subject>Liver - chemistry</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Microwaves</subject><subject>Organ Preservation</subject><subject>Paroxetine</subject><subject>Preservation</subject><subject>Psychotropic drugs</subject><subject>Psychotropic Drugs - analysis</subject><subject>Psychotropic Drugs - chemistry</subject><subject>Quetiapine</subject><subject>Room temperature</subject><subject>Solvents</subject><subject>Specimen Handling</subject><subject>Stability</subject><subject>Swine</subject><subject>Tandem Mass Spectrometry</subject><subject>Time 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Int</addtitle><date>2020-02</date><risdate>2020</risdate><volume>307</volume><spage>110136</spage><pages>110136-</pages><artnum>110136</artnum><issn>0379-0738</issn><eissn>1872-6283</eissn><abstract>•Porcine liver homogenates (PLHs) added with psychotropic drugs were formalin-fixed.•Drug concentrations after formalin fixation were analyzed periodically for 6 months.•Residual ratios of all drugs except for estazolam were >10 % after 4 weeks.•Residual ratios of 5 out of 10 drugs were >25 % even after 6 months.•Formalin-fixed PLHs could be useful samples in forensic toxicology.
In forensic toxicology studies, drug concentrations must be estimated by the analytical data of formalin-fixed tissues if fresh or frozen tissue specimens are not available. We wished to investigate the stability and time-course of metabolism/degradation of drugs in formalin-fixed tissues using porcine liver homogenates (PLHs) instead of human tissue. Ten psychotropic drugs (amitriptyline, brotizolam, diazepam, diphenhydramine, estazolam, etizolam, levomepromazine, paroxetine, quetiapine and triazolam) were added to PLHs. After the PLHs had been fixed with neutral buffered formalin at room temperature, the concentrations of the drugs in the PLHs were determined by liquid chromatography–tandem mass spectrometry after 3 days, 1 week, 2 weeks, 4 weeks, 2 months, 4 months and 6 months. After 6 months, the residual ratio of amitriptyline, diphenhydramine and quetiapine was 80 %–95 %; that of diazepam, paroxetine and triazolam was 10 %–45 %; and that of brotizolam, etizolam and levomepromazine was 1 %–5 %. Estazolam was not detected from the first day of formalin fixation. These data suggest that the concentrations of drugs in PLHs measured after formalin fixation decreased to varying degrees compared with their initial concentrations. These time-dependent changes in drug concentration were due to degradation during preservation in formalin solution and metabolism by hepatic microsomal enzymes.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>31896021</pmid><doi>10.1016/j.forsciint.2019.110136</doi></addata></record> |
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| subjects | Amitriptyline Animals Benzodiazepines Chemicals Chromatography Chromatography, Liquid Degradation Diazepam Diphenhydramine Drug metabolism Drug Stability Drugs Fixation Fixatives Forensic science Forensic sciences Forensic toxicology Forensic Toxicology - methods Formaldehyde Formalin-fixed tissues Human tissues LC–MS/MS Liquid chromatography Liver Liver - chemistry Mass spectrometry Mass spectroscopy Microwaves Organ Preservation Paroxetine Preservation Psychotropic drugs Psychotropic Drugs - analysis Psychotropic Drugs - chemistry Quetiapine Room temperature Solvents Specimen Handling Stability Swine Tandem Mass Spectrometry Time dependence Tissues Toxicology Triazolam Vortices |
| title | Stability of ten psychotropic drugs in formalin-fixed porcine liver homogenates |
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