title: Identification and quantification of 8 sulfonylureas with clinical toxicology interest by liquid chromatography-ion-trap tandem mass spectrometry and library searching.
abstract: BACKGROUND
  Identification of sulfonylureas in blood may be useful in the evaluation of hypoglycemic crises of unknown origin. The aim of the present study was to develop a highly selective liquid chromatography-electrospray tandem mass spectrometry (MS-MS) method using an ion-trap detector for rapid screening, identification, and quantification of sulfonylureas in human plasma.
  
  
  METHODS
  After standard liquid-liquid extraction with glisoxepide as an internal standard, 8 sulfonylureas (glibenclamide, glipizide, gliclazide, glibornuride, glimepiride, carbutamide, chlorpropamide, and tolbutamide) were eluted from a C18 column within 10 min with an isocratic mobile phase. Drugs were identified and quantified in full-scan MS-MS mode by use of a homemade MS-MS library. We used the assay in 134 cases of hypoglycemic crises of unknown origin.
  
  
  RESULTS
  No ion suppression effect was noted for the analytes at their specific retention-time windows. For all drugs, assay validation showed good linearity (r2>0.990) and acceptable imprecision and recovery based on commonly used criteria of acceptance. The mean extraction recoveries were 63%-87% for 5 sulfonylureas but <45% for 3 (carbutamide, chlorpropamide, and tolbutamide). Nevertheless, the high sensitivity of the MS instrument made possible detection and quantification of all 8 drugs at subtherapeutic to toxic concentrations with good precision. Sulfonylureas were found in 9 hypoglycemic patients.
  
  
  CONCLUSIONS
  The described assay method allows accurate, rapid identification and quantification of 8 sulfonylureas in human plasma and can be used for specific diagnosis of factitious hypoglycemia caused by ingestion of these drugs.
authors: Laboratoire de Pharmacologie et Toxicologie, Hôpital Maison Blanche, CHU de Reims, France. ghoizey@chu-reims.fr
authors: Guillaume
authors: G
authors: Hoizey
authors: Denis
authors: D
authors: Lamiable
authors: Thierry
authors: T
authors: Trenque
authors: Arnaud
authors: A
authors: Robinet
authors: Laurent
authors: L
authors: Binet
authors: Matthieu L
authors: ML
authors: Kaltenbach
authors: Sandrine
authors: S
authors: Havet
authors: Hervé
authors: H
authors: Millart
mesh_terms: D002853:Chromatography, Liquid; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000175:diagnosis; D007004:Hypoglycemic Agents / Q000097:blood* / Q000506:poisoning; D008297:Male; D008875:Middle Aged; D009110:Munchausen Syndrome / Q000139:chemically induced / Q000175:diagnosis; D021241:Spectrometry, Mass, Electrospray Ionization; D013453:Sulfonylurea Compounds / Q000097:blood* / Q000506:poisoning; D014116:Toxicology / Q000379:methods
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds