ABSTRACT
OBJECTIVE: To develop an LC-MS/MS method for the determination of vonoprazan pyroglutamate and vonoprazan fumarate in rat urine to determince the urine excretion of the two drugs in SD rats. METHODS: The detection was performed on an API 4000 tandem mass spectrometer equipped with an electrospray ionization (ESI) source. Multiple reaction monitoring (MRM) was selected with the transitions of m/z 346.2 to 315.2 for TAK-438 P and m/z 237.2 to 194 for IS, respectively. Separation of the analytes was achieved by a Shimadzu liquid chromatography system with an Agelient C18 analytical column (4.6 mm×150 mm, 3.5 μm). Isocratic elution was adopted with mobile phase A (10 mmol•L-1 ammonium acetate and 0.1% formic acid) and mobile phase B (methanol) at the ratio of 40:60, at a flow rate of 0.6 mL•min-1. The total run time was 6 min and the injected sample volume was 5 μL. All the features of the developed method suggested it met the criteria for bioanalytical METHODS recommended by regulatory authorities. The accumulative urine excretion rates of TAK-438 F and TAK-438 P were determined after oral administration of TAK-438 P and equimolar TAK-438 F in SD rats. RESULTS: The accumulative urine excretion rates of the prototype drugs were 2.11% and 2.03%, respectively. The low excretion rates indicated that metabolism might be the major clearance mechanism of TAK-438 P and TAK-438 F. CONCLUSION: This was the first time to establish and validate a simple, rapid and sensitive LC-MS/MS method for the quantification of TAK-438 P. There is no significant difference of the accumulative urine excretion rate between TAK-438 P and TAK-438 F in SD rats, which provides the basis for the druggability of TAK-438 P.
ABSTRACT
Proton pump inhibitors (PPIs) are widely used in clinical practice from early 1990s for the treatment of acid- related diseases. PPIs are superior to histamine2-receptor antagonists or anticholinergic agents. These drugs have proven to be effective, safe and well-tolerated during the past two decades. This brief review presents the pharmacodynamics and pharmacokinetics of PPIs and presents clincal applications of the drugs in acid-related diseases.
Subject(s)
Humans , Gastric Acid/metabolism , Gastrointestinal Agents/pharmacokinetics , Proton Pumps/antagonists & inhibitorsABSTRACT
Objective: To investigate the correlation between gastric acid pH value of patients with acid-related gastric diseases and the score of their life events. Methods: To evaluate the LES (life event scale) of the 108 patients with acid-related diseases were divided into 3 groups according their cluster of gastric acid pH value, group one pH 1.3 (n=37), group two pH 1.6~1.7(n=32), group three pH 2.1~4.5(n=39). Results: The LES total score and factor scores increased with the gastric acid level, the total score of the three groups were 40.0?20.6, 15.1?9.2, 6.4?6.5 respectively, the differences among the three groups were significant (F=43.26,P