Urine Excretion of Vonoprazan Pyroglutamate in SD Rats
QIAO Yuan1, HUANG Jian-lin1, WANG Qing-wei2*, LIANG Jia-long3, WANG Li-bin3, JING Juan3
1. Department of Clinical pharmacy, Affiliated Hospital of Yan��an University, Yan'an, 716000, China; 2. Department of Pharmacy, Tangdu Hospital, The Fourth Military Medical University, Xi��an, 710038, China; 3. Department of Medicinal Chemistry, School of Pharmacy, The Fourth Military Medical University, Xi��an, 710032, China
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 ��m). 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 ��L. 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.
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2018, Vol. 53 
