A Robust Method for Simultaneous Detection of β-HydroxybutyricAcid and Glucose in In Vivo Samples for Diabetic Ketoacidosis Research

Diabetic ketoacidosis is a potentially lethal complication of diabetes. Glucose and β-hydroxybutyric acid (β-HB, BHB) are the primary clinical indicators in the early stage of diabetic ketoacidosis. Monitoring glucose and β-hydroxybutyric acid will help the early diagnosis and prevention of deterioration of ketoacidosis for diabetic patients.

Conventional determination uses ELISA kit to detect the glucose and β-hydroxybutyric acid, respectively. For in vivo samples of lab research, derivatization method was reported for β-hydroxybutyric acid analysis with the LC-MS/MS platform. Both ELISA and derivatization are complicate and time consuming, therefore, directly determine the ratio of β-hydroxybutyric acid in plasma is necessary. In this study, a robust method to simultaneously detect β-HB and glucose for in vivo samples was developed without multiple-step derivatization. HILIC LC mode coupled with triple-quad mass spectrum was applied. The analysis time was reduced from 5 min/sample to 3.5 min/sample for testing both biomarkers. The detect limitation met the requirement for diabetic ketoacidosis research.