Development and validation of an LC-MS/MS sulfonylurea assay for hypoglycemia cases in the emergency department.

Overview

BACKGROUND: Sulfonylureas are antidiabetic agents widely prescribed for the treatment of type-II diabetes. Detection of the presence of sulfonylureas in cases of unexplained hypoglycemia rules out other underlying pathophysiological conditions. The goal of this study was to develop and validate a qualitative liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for the rapid identification of sulfonylureas in serum. METHODS: An LC-MS/MS assay was developed using an Agilent HPLC with an AB Sciex 3200 LC-MS/MS operating in ESI positive mode. Linearity, LOD, precision, matrix effect, recovery, carry-over and stability of the final method were evaluated for method validation. Concordance with another clinically validated LC-MS/MS method was evaluated using remnant samples from patients prescribed a sulfonylurea. RESULTS: The assay performed well with all validation data meeting pre-determined criteria. The method comparison study showed a correlation coefficient of 0.99 for glipizide, the most common sulfonylurea, despite both methods being validated as qualitative methods. To date the validated assay has been utilized in 19 cases of unexplained hypoglycemia presenting to the emergency department, in which 5 were sulfonylurea positive. CONCLUSION: We have developed a rapid and sensitive LC-MS/MS sulfonylurea assay, and utilized this assay to assist in the differential diagnosis of unexplained hypoglycemia.