Study on pharmacokinetics and bioequivalence of Vonoprazan pyroglutamate in rats by liquid chromatography with tandem mass spectrometry

Vonoprazan Fumarate (TAK-438 F) is a new and effective drug approved in Japan in 2014 for treatment and prevention of acid-related diseases (ARDs), which exhibits many advantages compared with traditional proton-pump inhibitors (PPIs). However, the clinical applications of TAK0-438 F suffers limitation due to the lack of injection dosage form. Efforts to overcome this limitation lead to the systhesis of Vonoprazan pyroglutamate (TAK-438 P) for its high water solubility and more potent antisecretory effect. This was the first report to establish and validate a reliable and sensitive LC-MS/MS method for the quantification of TAK-438 P in rat plasma and tissues (heart, liver, spleen, liver, kidney, rain, stomach and small intestine). All the features of the developed method suggested it was within bioanalytical criteria recommended by regulatory authorities. Furthermore, the developed method was applied to the exploration of the bioequivalence between TAK-438 P and TAK-438 F, as well as the pharmacokinetics and tissue distribution of TAK-438 P. The results showed that there was no significant differences between TAK-438 P and TAK-438 F after oral administration of the same dose. Besides, TAK-438 P was rapidly absorbed and eliminated in rat plasma. And it was widely distributed and there was no long-term accumulation in most tissues. Notably, more than 2000 ng/mL was observed in stomach 12 h after oral administration. The high accumulation revealed that stomach was likely to be the target organs of TAK-438 P.