Abstract : : More than fifty years after their marketing, sulfonylureas remain one of the most prescribed drugs for the treatment of non-insulino-dependent diabetes mellitus. However, these products are sometimes responsible of unexplained and severe hypoglycaemias observed in patient without diabetic pathology. These typical hypoglycemias, qualified as factious, are one of the clinical expressions of the Munchausen syndrome, a psychiatric disorder characterized by the need for the subject to simulate a pathology. The hypoglycemia is associated with an endogenous hyperinsulinism, also observed in a rare endocrine pathology, the insulinoma. This article aims to show the interest of the determination of sulfonylureas in blood for the differential diagnostic of endogenous hyperinsulinisms. The confirmation of a factious hypoglycemia is capital to avoid a partial or subtotal pancreatectomy, surgical treatment when an insulinoma is suspected. Ultra liquid chromatography coupled with the mass spectrometry tandem (UPLC -MS -MS ) technique had been used. The technique allowed the identification and quantification of the most used sulfonylureas and repaglinide in blood, and will be a method of choice to confirm a non-appropriate consumption of sulfonylureas.