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–MS-MS in Blood of the Two Cases

Arbouche, Nadia; Godard, Estelle; Gheddar, Laurie; Raul, Jean‐Sébastien; Kintz, Pascal

doi:10.1093/jat/bkab097

Cited by 7 publications

(9 citation statements)

References 19 publications

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“…After removing 196 duplicate records, an initial screening of 229 records was done and led to the exclusion of 187 articles. Further, a full-text review excluded 31 articles due to the following reasons: non-English articles (n = 29) (Derobert L et al, 12 Domart A et al, 13 Lenhardt A, 14 Richter R, 15 Szabo Z et al, 16 Chlud K, 17 Sachsse B, 18 Bourgeois M et al, 19 Vincent V et al, 20 Creutzfeldt W et al, 21 Euler-Rolle J et al, 22 Stofer A et al, 23 Tourniaire J et al, 24 Holldorf L et al, 25 Marigo S et al, 26 Bourgeois M, 27 Stefan J, 28 Zilker T et al, 29 Schneider V et al, 30 Hambrecht M et al, 31 Logemann E et al, 32 von Albert H et al, 33 Szponar J et al, 34 Wehner F et al, 35 Nikoli c S et al, 36 Klimaszyk D et al, 37 Uesugi K, 38 Chen L et al, 39 Tong F et al, 40 and articles that could not be retrieved (n = 2) (Lionte C et al, 41 Arbouche N et al 42 ). From the primary search of the databases 11 records met the inclusion criteria.…”

Section: Resultsmentioning

confidence: 99%

Suicide and attempted suicide by insulin: A systematic review

Assad

Alawami²,

Khatem³

et al. 2023

F1000Res

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Background: Intentional insulin overdose either in people with diabetes or without can be used to attempt suicide. Massive insulin administration may result in coma and unexplained hypoglycemia. In this study, we aim at reviewing the demographic data of suicidal cases, the relation of psychiatric illness to dying by suicide and attempting suicide using insulin, route of insulin administration and outcome, post-mortem findings in suicide by insulin and collaborative evidence, initial presentation, blood glucose level and complications in attempting suicide cases. Methods: PubMed, Web of Science, and Scopus databases were searched on October 4, 2021, using a comprehensive strategy review. The following search terms were applied: (Insulin) AND (toxicity OR overdose OR toxicology OR poisoning OR intoxication) AND (Suicide OR attempted suicide OR Self-harm OR Self harm). The search strategy was set based on PRISMA guideline; 11 papers were eligible for inclusion and additional 23 studies were added from the citation search. All English articles related to suicide and attempted suicide using insulin were included and no specific timeline or filter was used. Any non-English article and accidental or homicidal cases were excluded from the review. Results: The analysis included 179 victims, aged between 13 to 76 years with male predominance and people with diabetes, especially T1DM, having higher prevalence, with subcutaneous injection being the most common route of administration. In addition, psychiatric illnesses and multiple suicide attempts were identified in many cases besides the use of insulin in a combination with other medications. Conclusions: Dying by suicide using insulin is uncommon, however, as diabetes mellitus prevalence increases worldwide, it is expected that intentional insulin overdose will also increase. Furthermore, psychiatric illnesses and easy access to insulin are important factors that should be put into consideration.

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Section: Resultsmentioning

confidence: 99%

Suicide and attempted suicide by insulin: A systematic review

Assad

Alawami²,

Khatem³

et al. 2023

F1000Res

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“…The method used for the analysis of the blood sample has been previously validated and published [12].…”

Section: Resultsmentioning

confidence: 99%

“…For the identification and quantification of insulins in blood, a previously validated and published method was used [12]. All the chemical reagents, the extraction procedure and LC-HRMS parameters are reported in the previous published paper.…”

Section: Me Thodsmentioning

confidence: 99%

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Intentional overdose of glargine insulin: Determination of the parent compound in postmortem blood by LC‐HRMS

Arbouche

Walch

Raul

et al. 2023

Journal of Forensic Sciences

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Insulin glargine is a long‐acting insulin analog that is converted after enzymatic cleavage of the arginine pair of the β‐chain into its main metabolite M1 (21A‐Gly‐insulin), which is responsible for the hypoglycemic activity. In all the overdose cases described in the literature, only M1 concentrations have been reported, whereas insulin glargine was always absent or below the limit of quantitation. In this study, we present a case of suicide of a young nurse by injection of insulin glargine in which the parent molecule was found at a toxic concentration in blood. The determination and the discrimination of insulin glargine from human insulin and other synthetic analogs in the blood specimen were performed by liquid chromatography coupled to high‐resolution mass spectrometry (Waters XEVO G2‐XS QToF) and extraction after precipitation in the presence of bovine insulin (internal standard), with a mixture of acetonitrile/methanol +1% formic acid followed by purification on solid phase extraction cartridges C18. Glargine insulin tested highly positive in the blood with a concentration of 1.06 mg/L. Due to the difficulty in obtaining a M1 pure standard, the metabolite could not be dosed. This unique presence of the parent molecule, reported for the first time, can be explained by inter‐individual variability in the rate of conversion to metabolite. Intravenous injection versus subcutaneous injection can also explain the presence of insulin glargine. Finally, the dose injected may have been so high that saturation of the proteolytic enzymes responsible for conversion to M1 should have occurred.

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“…Recently, specific and sensitive analytical methods for insulin preparations using mass spectrometry have been developed, and insulin detection and quantification in biological and postmortem samples have been reported [5,8,[10][11][12]. However, few reports have examined the concentration of insulin preparations in postmortem samples and their involvement in the cause of death, making postmortem evaluation of insulin concentration remains difficult.…”

Section: Introductionmentioning

confidence: 99%

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

Yamaguchi

Chiba

Torimitsu

et al. 2023

Journal of Forensic Sciences

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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.

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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–MS-MS in Blood of the Two Cases

Cited by 7 publications

References 19 publications

Suicide and attempted suicide by insulin: A systematic review

Suicide and attempted suicide by insulin: A systematic review

Intentional overdose of glargine insulin: Determination of the parent compound in postmortem blood by LC‐HRMS

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

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