Abstract
Objectives
Since melperone abuse with lethal intoxication is common, expert opinions based on therapeutical and lethal concentration ranges can be considered as important. Because there is a lack of information about fatalities caused by melperone mono-intoxications and data on tissue samples with concentration distribution, the aim of this work is the examination of lethal concentration ranges of melperone and drug quantification in different matrices.
Methods
An LC-MS/MS method was applied for analyses performed in blood and tissue samples. Quantification based on standard addition and sample preparation on liquid–liquid extraction with 1-chlorobutane. An appropriate tissue homogenization was performed ahead of extraction with an IKA Ultra-Turrax-Tube-Drive®. A Luna 5 µm C18 (2) 100 Å, 150 × 2 mm analytical column was used for chromatographic separation and the elution was performed with two mobile phases consisted of A (H2O/methanol = 95/5, v/v) and B (H2O/methanol = 3/97, v/v) both with 10 mM ammonium acetate and 0.1% acetic acid.
Results
A multi-drug LC-MS/MS analytical method developed was applied successfully for melperone quantification in different post-mortem matrices. No analytical problems could be identified during method development and analyses of real samples. The melperone lethal concentration calculated in femoral blood of the drug mono-intoxication investigated was 10 mg/L. Melperone concentration distribution was presented for the first time.
Conclusions
The lethal reference concentration of melperone in femoral blood of 17.1 mg/L pointed out in different reference lists should be used with caution. Instead, a lower lethal melperone concentration should be considered. The post-mortem concentration distribution of the drug presented could be helpful in the interpretation of cases where no blood samples are available.
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Research funding: None declared.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Ethical approval: Not applicable.
References
1. Baselt, RC. Disposition of toxic drugs and chemicals in men, 9th ed. Seal Beach: Biomedical Publications; 2011.Search in Google Scholar
2. Schulz, M, Iwersen-Bergmann, S, Andresen, H, Schmoldt, A. Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics. Crit Care 2020;16:R136.10.1186/cc11441Search in Google Scholar
3. Chan, KY, Okerholm, RA. Quantitative analysis of melperone in human plasma by gas chromatography-mass spectrometry-selected ion monitoring. J Chromatogr 1983;274:121–7. https://doi.org/10.1016/s0378-4347(00)84415-1.Search in Google Scholar
4. Saar, E, Beyer, J, Gerostamoulos, Drummer, OH. The analysis of antipsychotic drugs in human matrices using LC-MS(/MS). Drug Test Anal 2012;4:376–94. https://doi.org/10.1002/dta.1337.Search in Google Scholar
5. Kratzsch, C, Peters, FT, Kraemer, T, Weber, AA, Maurer, HH. Screening, library-assisted identification and validated quantification of fifteen neuroleptics and three of their metabolites in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization. J Mass Spectrom 2003;38:283–95. https://doi.org/10.1002/jms.440.Search in Google Scholar
6. Methling, M, Krumbiegel, F, Alameri, A, Hartwig, S, Parr, MK, Tsokos, M. Concentrations of antidepressants, antipsychotics, and benzodiazepines in hair samples from postmortem cases. SN Compr Clin Med 2020;2:284–300. https://doi.org/10.1007/s42399-020-00235-x.Search in Google Scholar
7. Josefsson, M, Kronstrand, R, Andersson, J, Roman, M. Evaluation of electrospray ionisation liquid chromatography-tandem mass spectrometry for rational determination of a number of neuroleptics and their major metabolites in human body fluids and tissues. J Chromatogr B 2003;789:151–67. https://doi.org/10.1016/s1570-0232(03)00207-1.Search in Google Scholar
8. Remane, D, Meyer, MR, Wissenbach, DK, Maurer, HH. Ultra high performance liquid chromatographic-tandem mass spectrometric multi-analyte procedure for target screening and quantification in human blood plasma: validation and application for 31 neuroleptics, 28 benzodiazepines, and Z-drugs. Anal Bioanal Chem 2011;401:1341–52. https://doi.org/10.1007/s00216-011-5187-9.Search in Google Scholar PubMed
9. Saar, E, Gerostamoulos, D, Drummer, OH, Beyer, J. Identification and quantification of 30 antipsychotics in blood using LC-MS/MS. J Mass Spectrom 2010;45:915–25. https://doi.org/10.1002/jms.1783.Search in Google Scholar PubMed
10. Dziadosz, M, Teske, J, Klintschar, M, Nordmeier, F. LC–MS/MS screening strategy for cannabinoids, opiates, amphetamines, cocaine, benzodiazepines and methadone in human serum, urine and post-mortem blood as an effective alternative to immunoassay based methods applied in forensic toxicology for preliminary examination. Forensic Chem 2018;7:33–7. https://doi.org/10.1016/j.forc.2017.12.007.Search in Google Scholar
11. Henning, K, Teske, J, Klintschar, M, Dziadosz, M. Postmortem findings of pipamperone after fatal intoxications and its distribution in body fluids and tissues. Drug Test Anal 2019;11:626–30. https://doi.org/10.1002/dta.2574.Search in Google Scholar PubMed
12. Peters, FT, Drummer, OH, Musshoff, F. Validation of new methods. Forensic Sci Int 2007;165:216–24. https://doi.org/10.1016/j.forsciint.2006.05.021.Search in Google Scholar
13. Musshoff, F, Padosch, S, Steinborn, S, Madea, B. Fatal blood and tissue concentrations of more than 200 drugs. Forensic Sci Int 2004;142:161–210. https://doi.org/10.1016/j.forsciint.2004.02.017.Search in Google Scholar
14. Stein, S, Schmoldt, A, Schulz, M. Fatal intoxication with melperone. Forensic Sci Int 2000;113:409–13. https://doi.org/10.1016/s0379-0738(00)00201-2.Search in Google Scholar
15. Söderberg, C, Wernvik, E, Tillmar, A, Spigset, O, Kronstrand, R, Reis, M, et al.. Antipsychotics – postmortem fatal and non-fatal reference concentrations. Forensic Sci Int 2016;266:91–101. https://doi.org/10.1016/j.forsciint.2016.05.002.Search in Google Scholar PubMed
16. Skopp, G. Leichentoxikologie. Rechtsmedizin 2008;18:473–85. https://doi.org/10.1007/s00194-008-0563-2.Search in Google Scholar
17. Drummer, OH, Kennedy, B, Bugeja, L, Ibrahim, JE, Ozanne-Smith, J. Interpretation of postmortem forensic toxicology results for injury prevention research. Inj Prev 2013;19:284–9. https://doi.org/10.1136/injuryprev-2012-040488.Search in Google Scholar PubMed
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Articles in the same Issue
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- Interpretation of melperone intoxication: post-mortem concentration distribution and interpretation of intoxication data
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- Case Report
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Articles in the same Issue
- Frontmatter
- Review
- Pharmacogenetics of common SNP affecting drug metabolizing enzymes: comparison of allele frequencies between European and Malaysian/Singaporean
- Original Articles
- Association of genetic polymorphisms in vitamin D receptor (ApaI, TaqI and FokI) with vitamin D and glycemic status in type 2 diabetes patients from Southern India
- Addressing the standardisation of internal standards and preservative used in human bio fluids for NMR analysis: a method optimization
- Follow up: palmitic acid ester of tetrahydrocannabinol (THC) and palmitic acid diester of 11-hydroxy-THC – unsuccessful search for additional THC metabolites
- Co-expression of drug metabolizing cytochrome P450 enzymes and estrogen receptor alpha (ESR1) in human liver: racial differences and the regulatory role of ESR1
- Pharmacokinetics of solid lipid Boswellia serrata particles in healthy subjects
- Long-term consumption of Moringa oleifera-supplemented diet enhanced neurocognition, suppressed oxidative stress, acetylcholinesterase activity and neuronal degeneration in rat’s hippocampus
- Interpretation of melperone intoxication: post-mortem concentration distribution and interpretation of intoxication data
- Effect of zoledronic acid on bone nanocomposites organization and prevention of bone mineral density loss in ovariectomized rats
- Case Report
- Effect of gliding cupping with Roghan-e-Surkh in low back ache (Waja-uz-Zahr): a case series study