Preclinical pharmacokinetics of trigonelline using ultra‐performance liquid chromatography–tandem mass spectrometry and pharmacological studies targeting type 2 diabetes

Abstract Trigonelline is a quaternary base alkaloid and zwitterionic complex that acts by affecting β‐cell regeneration and insulin secretion. Tr inhibits enzymatic activities, lowering the blood glucose and lipid levels due to which it is used in the treatment of co‐morbid diseases such as diabetes, Alzheimer's, etc. Herein, it was aimed to develop a bioanalytical method for estimation of Tr using ultra‐performance liquid chromatography–tandem mass spectrometry and explore the pharmacokinetic profile. The anti‐diabetic, antilipidemic efficacy studies of Tr in the high‐fat diet‐induced streptozotocin‐diabetic rat model was also explored. The separation of analyte was achieved with acetonitrile and 0.1% formic acid (20:80) with a flow of 0.4 mL/min. The ionization of the analyte was achieved in positive electrospray ionization mode with the precursor to product ion transitions of Tr (138.14 > 94), and Trigonelline D 3 (143.19 > 97.13). The validated assay was effectively applied for the estimation of compartmental pharmacokinetic by using Phoenix WinNolin8.0 (Certera™, USA) and it was observed that the Tr follow two compartmental pharmacokinetic model. The experimental results also suggest that Tr distributed through the central compartment to the peripheral compartment and redistributed to the central compartment. In addition, Tr exhibited significant anti‐hyperglycemic and antihyperlipidemic efficacy against high‐fat diet‐induced streptozotocin‐induced type 2 diabetic rats.