Identification, measurement, and evaluation of blood concentrations of insulin glargine and insulin lispro by UPLC-MS-MS in a dead body suspected of insulin overdose.


Journal

Journal of forensic sciences
ISSN: 1556-4029
Titre abrégé: J Forensic Sci
Pays: United States
ID NLM: 0375370

Informations de publication

Date de publication:
Mar 2023
Historique:
revised: 25 01 2023
received: 27 09 2022
accepted: 25 01 2023
pubmed: 11 2 2023
medline: 4 3 2023
entrez: 10 2 2023
Statut: ppublish

Résumé

Insulin preparations, which are drug treatments for diabetes, cause fatal hypoglycemia when an overdose is administered. Cases of homicide and suicide using these preparations have been reported and are of great forensic interest. However, there are few reports assessing the postmortem concentration of insulin preparations, and it is often difficult to determine the cause of death. In the present study, we report a case of a suspected insulin glargine and insulin lispro overdose for suicide. A woman in her 30s had a history of mental illness and diabetes. The day before her death, she reported to her boyfriend that she had taken large doses of insulin preparations and prescription drugs. An autopsy revealed no fatal injuries or lesions. Drug screening tests revealed several prescription drugs, none of which showed toxic concentrations. Analysis using LC-MS/MS detected insulin glargine in the peripheral and cardiac blood at 429 μU/mL and 1362 μU/mL, respectively, whereas insulin lispro was detected in both the peripheral and cardiac blood at levels below the lower limit of quantification (LLOQ; <50 μU/mL). The cause of death was considered likely to be hypoglycemia caused by an overdose of insulin glargine. Insulin glargine is rapidly metabolized after subcutaneous administration and is rarely detected in the blood when used at therapeutic doses. There are no other reports on the quantification of insulin glargine parent compounds in postmortem samples, and this case provides important data on postmortem blood concentrations of insulin glargine intoxication.

Identifiants

pubmed: 36762764
doi: 10.1111/1556-4029.15219
doi:

Substances chimiques

Insulin Glargine 2ZM8CX04RZ
Insulin Lispro 0
Hypoglycemic Agents 0
Insulin, Long-Acting 0
Blood Glucose 0
Insulin 0

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

704-710

Subventions

Organisme : Japan Society for the Promotion of Science
ID : 19K19481

Informations de copyright

© 2023 American Academy of Forensic Sciences.

Références

World Health Organization. Definition, diagnosis, and classification of diabetes mellitus and its complications. Available from: https://apps.who.int/iris/bitstream/handle/10665/66040/WHO_NCD_NCS_99.2.pdf?sequence=1&isAllowed=y (1999). Accessed 25 Jan 2023.
Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103:137-49. https://doi.org/10.1001/jamaophthalmol.2022.0050
American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes - 2020. Diabetes Care. 2020;43:S98-110. https://doi.org/10.2337/dc20-S009
Baud JF, Deye N, Sonneville R, Megarbane B. Intoxication grave par l'insuline [Acute severe insulin poisoning]. Réanimation. 2006;15(6):481-9. https://doi.org/10.1016/j.reaurg.2006.09.001
Arbouche N, Godard E, Gheddar L, Raul JS, Kintz P. Attempted murder of a young child followed by an attempted suicide of the mother by injection of insulin aspart: identification of quantification of insulin by LC-HRMS and UPLC-MA/MA in blood of the two cases. J Anal Toxicol. 2021;41:e65-72. https://doi.org/10.1093/jat/bkab097
Bottinelli C, Nicoli R, Bevalot F, Cartiser N, Roger C, Chikh K, et al. Development and validation of a method for quantification of human insulin and its synthetic analogues in plasma and post-mortem sera by LC/MS/HRMS. Talanta. 2021;225:122047. https://doi.org/10.1016/j.talanta.2020.122047
Hess C, Madea B, Daldrup T, Musshoff F. Determination of hypoglycemia induced by insulin or its synthetic analogues post mortem. Drug Test Anal. 2013;5:802-7. https://doi.org/10.1002/dta.1500
Sunderland N, Wong S, Lee CK. Fatal insulin overdoses: case report and update on testing methodology. J Forensic Sci. 2016;61(Suppl 1):S281-4. https://doi.org/10.1111/1556-4029.12958
Tong F, Wu R, Huang W, Yang Y, Zhang L, Zhang B, et al. Forensic aspects of homicides by insulin overdose. Forensic Sci Int. 2017;278:9-15. https://doi.org/10.1016/j.forsciint.2017.06.015
Blackburn M. Advances in the quantification of therapeutic insulin analogues by LC-MS/MS. Bioanalysis. 2013;5:2933-46. https://doi.org/10.1016/j.talanta.2020.122047
Legg KM, Labay LM, Aiken SS, Logan BK. Validation of a fully automated immunoaffinity workflow for the detection and quantification of insulin analogs by LC-MS-MS in postmortem vitreous humor. J Anal Toxicol. 2019;43:505-11. https://doi.org/10.1093/jat/bkz014
Chambers EE, Fountain KJ, Smith N, Ashraf L, Karalliedde J, Cowan D, et al. Multidimensional LC/MS/MS enables simultaneous quantification of intact human insulin and five recombinant analogs in human plasma. Anal Chem. 2014;86:694-702. https://doi.org/10.1021/ac403055d
Insulin glargine BS injection kit “FFP” [package insert]. Tokyo, Japan: FUJIFILM Corporation; 2016.
Rosskamp R, Park G. Long-acting insulin analogs. Diabetes Care. 1999;22(Suppl 2):B109-13.
Hilgenfeld R, Dorschung M, Geisen K, Neubauer H, Obermeier R, Seipke G, et al. Controlling insulin bioavailability by crystal contact engineering. Diabetologia. 1992;35:A193.
Berchtold H, Hilgenfeld R. Binding of phenol to R6 insulin hexamers. Biopolymers. 1999;51:165-72. https://doi.org/10.1002/(SICI)1097-0282(1999)51:2<165::AID-BIP6>3.0.CO;2-X
Insulin Lispro BS injection HU “Sanofi” [package insert]. Tokyo, Japan: Sanofi Japan; 2020.
Noble S, Johnson E, Walton B. Insulin lispro: a fast-acting insulin analog. Am Fam Physician. 1998;57:279-86.
American Board of International Medicine®. Available from: laboratory-reference-ranges.pdf (abim.org) (2022). Accessed 25 Jan 2023.
ATC/DDD Index. WHO Collaborating Centre for Drug Statistics Methodology. Available from: https://www.whocc.no/atc_ddd_index/ (2018). Accessed 25 Jan 2023.
Martin S, Achim S, Hilke AS, Stefanie IB. Revisited: therapeutic and toxic blood concentrations of more than 1100 drugs and other xenobiotics. Crit Care. 2020;24(1):195. https://doi.org/10.1186/s13054-020-02915-5
Baselt R. Disposition of toxic drugs and chemicals in man. 12th ed. Foster City, CA: Biomedical Publications; 2020.
Palmiere C, Manigin P. Postmortem chemistry update part I. Int J Leg Med. 2012;126:187-98. https://doi.org/10.1007/s00414-011-0625-y
Palmiere C, Manigin P. Postmortem chemistry update part II. Int J Leg Med. 2012;126:199-215. https://doi.org/10.1007/s00414-011-0614-1
Zilg B, Alkass K, Kronstrand R, Berg S, Druid K. A rapid method for postmortem vitreous chemistry-deadside analysis. Biomolecules. 2022;12:32. https://doi.org/10.3390/biom12010032
Iwase H, Kobayashi M, Nakajima M, Takatori T. The ratio of insulin to C-peptide can be used to make a forensic diagnosis of exogenous insulin overdose. Forensic Sci Int. 2021;115:123-7. https://doi.org/10.1016/s0379-0738(00)00298-x
Musshoff F, Hess C, Madea B. Disorders of glucose metabolism: postmortem analysis in forensic cases-PartII. Int J Leg Med. 2011;125:171-80. https://doi.org/10.1007/s00414-010-0510-0
Lebowitz MR, Blumenthal SA. The molar ratio of insulin to C-peptide. An aid to the diagnosis of hypoglycemia due to surreptitious (or inadvertent) insulin administration. Arch Intern Med. 1993;153:650-5.
Wunder C, Kauert G, Toennes WS. Factors leading to the degradation/loss of insulin in postmortem samples. Forensic Sci Int. 2014;241:173-7. https://doi.org/10.1016/j.forsciint.2014.06.003
Marks V. Murder by insulin: suspected, purported and proven - a review. Drug Test Anal. 2009;1:162-76. https://doi.org/10.1002/dta.38
Bolli GB, Hahn AD, Schmidt R, Eisenblaetter T, Dahmen R, Heise T, et al. Plasma exposure to insulin glargine and its metabolites M1 and M2 after subcutaneous injection of therapeutic and supratherapeutic doses of glargine in subjects with type 1 diabetes. Diabetes Care. 2012;35:2626-30.
Thomas A, Brinkkotter P, Schanzer W, Thevis M. Metabolism of human insulin after subcutaneous administration: a possible means to uncover insulin misuse. Anal Chim Acta. 2015;897:53-61.
Kuerzel GU, Shukla U, Shcoltz HE, Pretorious SG, Wessels DH, Venter C, et al. Biotransformation of insulin glargine after subcutaneous injection in healthy subjects. Curr Med Res Opin. 2003;19:34-40. https://doi.org/10.1185/030079902125001416
Thomas A, Thevis M, Delahaut P, Bosseloir A, Schanzer W. Mass spectrometric identification of degradation products of insulin and its long-acting analogues in human urine for doing control purposes. Anal Chem. 2007;15:2518-24. https://doi.org/10.1021/ac062037t

Auteurs

Sayaka Nagasawa (S)

Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Laboratoly of Forensic Toxicology, Graduate School of Pharmaceutical, Chiba University, Chiba, Japan.

Rutsuko Yamaguchi (R)

Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Japan.

Fumiko Chiba (F)

Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Laboratoly of Forensic Toxicology, Graduate School of Pharmaceutical, Chiba University, Chiba, Japan.

Suguru Torimitsu (S)

Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Japan.

Hirotaro Iwase (H)

Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-Ku, Japan.

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