Toxicological and Biochemical Analyses of an Autopsy Case Involving Oral Overdose of Multiple Antidiabetic and Antihypertensive Drugs

Abstract

Oral antidiabetics can cause fatal hypoglycemia; although they can be chemically identified and quantified, biochemical investigations are important for assessing the biological consequences of an overdose. Such cases of overdose involving oral antidiabetics may involve other drugs for treating lifestyle-related diseases, particularly antihypertensives. Here, we report a toxicological and biochemical investigation of drugs and biochemical profiles in a fatal overdose involving multiple oral antidiabetics and antihypertensives. A 55-year-old woman died about 2 days after the ingestion of around 110 tablets of antidiabetics and antihypertensives that had been prescribed for her husband. A forensic autopsy and histological analysis demonstrated no evident pathology as the cause of death. A toxicological analysis suggested hypoglycemia and an overdose of antihypertensives as well as the retention of antidiabetics and diuretics in the pericardial fluid. A relatively low pericardial amlodipine concentration was observed, which may have been the result of its long half-life (slower distribution and reduction rate) and/or possible affinity with the myocardium. In addition, a biochemical analysis indicated hypoglycemia, without increased serum insulin and C-peptide, but with increased glucagon levels, as the possible influence of glibenclamide overdose. These observations suggest the usefulness of a combination of toxicological and biochemical analyses in postmortem investigations involving a fatal overdose of such drugs.

Determination of drugs in exhumed liver and brain tissue after over 9 years of burial by liquid chromatography‐tandem mass spectrometry—Part 1: Cardiovascular drugs

“…The column was dried using vacuum for 15 min. Elution was performed two times with 1.5 ml of a mixture of dichloromethane/isopropanol/25% ammonium hydroxide (8/2/0.9, v/v/v) 7 …”

“…Elution was performed two times with 1.5 ml of a mixture of dichloromethane/isopropanol/25% ammonium hydroxide (8/2/0.9, v/v/v). 7 For the second approach, the column was washed by using 1 ml of a mixture of phosphate buffer (pH 6)/methanol (4/1, v/v), 1-ml acetic acid (1M), and 1-ml n-hexane. After drying the column (see above), the analytes were eluted by dichloromethane (1.5 ml, two times).…”

Determination of drugs in exhumed liver and brain tissue after over 9 years of burial by liquid chromatography–tandem mass spectrometry—Part 2: Benzodiazepines, opioids, and further drugs

“…For one approach, washing of the column was performed with 1 mL pH 6 phosphate buffer, 1 mL 1 M acetic acid, and 1 mL methanol. “After drying the column” by vacuum (15 min), “elution was performed two times with 1.5 mL of a mixture of dichloromethane/isopropanol/25% ammonium hydroxide (8/2/0.9, v/v/v)” 1,7 …”

“…"After drying the column" by vacuum (15 min), "elution was performed two times with 1.5 mL of a mixture of dichloromethane/ isopropanol/25% ammonium hydroxide (8/2/0.9, v/v/v)". 1,7 For the other approach, washing was performed with 1 mL pH 6 phosphate buffer/methanol (4/1, v/v), 1 mL 1 M acetic acid, and 1 mL n-hexane. After drying, 1.5 mL dichlormethane was used two times to elute the analytes.…”