Insulin murder and the case of Colin Norris

Although insulin is an essential medicine and a life-saving drug, it has also been incriminated in many poisoning deaths; accidental, suicidal and some with malicious intent. Overdosing with insulin precipitates a life-threatening state of hypoglycemia and if untreated leads to coma, irreversible brain damage and death. Normally, the pancreatic β-cells secrete equimolar amounts of insulin and C-peptide into the portal venous blood, although under physiological conditions the plasma concentration ratio (insulin/C-peptide) is less than unity, because insulin is more susceptible to hepatic first-pass metabolism. A high ratio of insulin/C-peptide in plasma from a poisoned patient is compelling evidence that pharmaceutical insulin was administered, which does not contain C-peptide. The analysis of insulin and C-peptide was traditionally done by immunoassay methods (RIA and/or ELISA), although high resolution LC-MS/MS is more suitable for forensic purposes and permits the identification of insulin analogues. Use of insulin as a murder weapon is exemplified by the case of Colin Norris, a male nurse found guilty of murdering four elderly patients and the attempted murder of a fifth by injecting them with insulin. However, the prosecution evidence against Norris was mainly circumstantial and hearsay. Toxicological evidence against Norris consisted of a high insulin/C-peptide concentration ratio in plasma from one of the victims. This analysis was done by an immunoassay method at a clinical laboratory and not a forensic laboratory. Analytical procedures, including chain-of-custody routines, are more stringent at forensic laboratories. Since his conviction, some of the medical evidence against Norris has been called into question, especially the prevalence of spontaneous attacks of hypoglycemia in elderly and frail patients with co-morbidities.