Is a “toxic” death possible with gliclazide, an oral hypoglycemic drug, found at therapeutic concentration?

Self Cite

Sodium‐glucose cotransporter 1 inhibitors are a new class of drugs used for the treatment of type II diabetes. Due to their diuretic capabilities and the glycosuria they induce, these molecules cause effective weight loss that could attract the interest of a wider public than diabetics with all the health consequences knowing the adverse effects of these substances. In order to reveal a past exposure to these substances, hair analysis can be very useful especially in the medicolegal context. There are no data in the literature about gliflozin testing in hair. In this study, a method was developed for the analysis of three molecules belonging to the gliflozin family (dapagliflozin, empagliflozin and canagliflozin) using a liquid chromatography system coupled to tandem mass spectrometry. After decontamination with dichloromethane, gliflozins were extracted from hair following incubation in methanol in the presence of dapagliflozin‐d5. Validation showed acceptable linearity for all compounds between 10 and 10,000 pg/mg, with limit of detection and limit of quantification at 5 and 10 pg/mg, respectively. Repeatability and reproducibility were below 20% at three concentrations for all analytes. The method was subsequently applied to the hair of two diabetic subjects under dapagliflozin treatment. In one of the two cases, the result was negative, while in the second case, the concentration was 12 pg/mg. Due to the absence of data, it is difficult to explain the absence of dapagliflozin in the hair of the first case. Physico‐chemical characteristics of dapagliflozin could explain its bad incorporation in hair, making detection difficult even after daily treatment.

Section: Resultsmentioning

confidence: 99%

“…The hair analysis represented the only evidence of exposure to this substance. Subsequently, a number of articles have been published, which focused on the development of analytical methods for detecting the main families of oral antidiabetic drugs (sulfonylureas, metformin, glinides and gliptins) in hair 19,21–24 …”

Section: Resultsmentioning

confidence: 99%

First identification of dapagliflozin in human hair: Development of a new liquid chromatography with tandem mass spectrometry method

Arbouche¹,

Blanchot²,

Raul³

et al. 2023

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“…Unfortunately, not much data is available in the literature for hair analysis of antidiabetics 12–14 and almost none for metformin. Only Binz et al 12 have identified metformin in the hair with concentrations ranging from 11 to 101 pg/mg.…”

Section: Introductionmentioning

confidence: 99%

Development of a new GC–MS/MS method for the determination of metformin in human hair

Arbouche

Batt²,

Raul

et al. 2020

Self Cite

Diabetes mellitus is one of the most important public health challenges. Metformin (1,1‐dimethylbiguanide) represents the “gold standard” for the treatment of diabetes mellitus type 2. Despite its important role in reducing mortality and morbidity in the diabetic population, metformin is associated with an increased risk of stroke. To document exposure to a drug, hair is considered to be the specimen of choice to complement blood and urine, since it provides historical detail of a subject's chronic exposure to drug(s). Measuring hair concentration of metformin can be important for forensic toxicologists investigating criminal poisoning or Munchausen's syndrome by proxy. In clinical toxicology, drug monitoring using hair to document metformin observance has not yet been described. To document the interest of hair analysis for metformin, the authors have developed and validated a method using a gas‐chromatography tandem mass spectrometry system and applied it to authentic hair obtained from 9 diabetic patients under daily treatment. The validation procedure demonstrated a LOD an LOQ of 1 and 100 pg/mg, respectively and acceptable linearity, repeatability and reproducibility. The hair of the 9 patients tested positive in the low ng/mg range with concentrations ranging from 0.3 to 3.8 ng/mg. It seems obvious, in comparison with other drugs, that metformin is badly incorporated into hair, as the daily dosage varied from 1 to 3 g. Although limited in the number of subjects, the study allowed to postulate a possible correlation between daily dose and concentration in dark hair, while for light hair no correlation was found.

Suitability of Hair Testing in Medical Dispensing Errors: A Fatal Case of Gliclazide Poisoning

Riess,

Klinger,

Roussel

et al. 2024

A patient was prescribed a new treatment, 40 mg furosemide. Her pharmacist mistakenly dispensed 40 mg gliclazide instead. After 3 weeks of treatment, the patient was found in a coma, was hospitalised and died after a week. Hair sample was collected during post‐mortem examination and tested for gliclazide on three 2 cm sections, starting at the root end. Hair strands were decontaminated, segmented and incubated in the presence of diazepam‐d5, and a solid–liquid extraction has been performed. Finally, toxicological analyses were performed by UFLC Shimadzu Prominence ‐ MS/MS Sciex 6500 QTRAP. Gliclazide was found on the proximal (238 pg/mg), median (77 pg/mg) and distal (69 pg/mg) segments. The concentration in the proximal segment was largely higher than in the other two, which demonstrates repeated intake of gliclazide by the patient during at least the last 2 months before death. The lower concentrations in the medial and distal segments, as well as a part of the concentration in the proximal segment, may be linked to external hair contamination. These could be due to either radial sweat diffusion, possibly occurring in the last week hospitalisation of the patient, or to biological fluids contamination during post‐mortem examination. This case illustrates the opportunity to confirm slow and fatal chronic poisoning by gliclazide using hair analysis and shows the benefit of hair testing for the investigation of medical or dispensing errors.