Simultaneous quantification of tegoprazan and its major metabolite M1 in dog plasma using liquid chromatography-tandem mass spectrometry.

ABSTRACT

Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) recently approved in Korea as a next-generation therapeutics for gastric acid-related diseases. In the present study, we demonstrate a simple bioanalytical liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of tegoprazan and its major metabolite (M1) in dog plasma. The developed method is based on protein precipitation and LC-MS/MS, validated according to the regulatory guidance for bioanalytical method validation. The calibration curves were linear in the concentration range of 50 ng/mL-50 µg/mL and 5 ng/mL-5 µg/mL for tegoprazan and M1, respectively. The inter- and intra-day precisions were evaluated with a coefficient of variation of <15%, and the mean accuracy ranged 92.6%-105%. The method exhibited good sensitivity and specificity. The stability of bench-top (for 8 h), freeze-thaw (3 cycles), and processed-samples (for 24 h at 4 °C) was acceptable. Tegoprazan was stable in dog plasma for 6 weeks at -70 °C. In conclusion, we successfully established a method for the simultaneous quantification of tegoprazan and M1 in dog plasma, and the method was validated for specificity, sensitivity, linearity, matrix effects, recovery, accuracy, precision, and stability. Finally, we show that the method was successfully applied to a pharmacokinetic study in dogs.