Received on March 9, 2005
Accepted on June 13, 2005

Drug Monitoring and Toxicology

Identification and Quantification of 8 Sulfonylureas with Clinical Toxicology Interest by Liquid Chromatography-Ion-Trap Tandem Mass Spectrometry and Library Searching

¹ Laboratoire de Pharmacologie et Toxicologie, Hôpital Maison Blanche, CHU de Reims, France
² Laboratoire de Pharmacologie et Toxicologie, Hôpital Maison Blanche, CHU de Reims, France, and Centre Régional de Pharmacovigilance, CHU de Reims, France
³ Laboratoire de Pharmacologie et de Pharmacocinétique, UFR de Pharmacie, Reims, France
⁴ Centre Régional de Pharmacovigilance, CHU de Reims, France

^* To whom correspondence should be addressed. E-mail: ghoizey{at}chu-reims.fr.

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.

Conclusion: 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.