Identification and quantification of 8 sulfonylureas with clinical toxicology interest by liquid chromatography-ion-trap tandem mass spectrometry and library searching.
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.
Hoizey
Guillaume
G
Laboratoire de Pharmacologie et Toxicologie, Hôpital Maison Blanche, CHU de Reims, France. ghoizey@chu-reims.fr
Lamiable
Denis
D
Trenque
Thierry
T
Robinet
Arnaud
A
Binet
Laurent
L
Kaltenbach
Matthieu L
ML
Havet
Sandrine
S
Millart
Hervé
H
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
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds