title: A validated simultaneous quantification method for vonoprazan (TAK-438F) and its 4 metabolites in human plasma by the liquid chromatography-tandem mass spectrometry.
abstract: Vonoprazan fumarate (TAK-438) is a potassium-competitive acid blocker which was approved in Japan for a treatment of acid-related diseases. In this study a simple and validated bioanalytical method, which can simultaneously determine vonoprazan (TAK-438F) and its four metabolites (M-I, M-II, M-III and M-IV-Sul) in human plasma, was developed. The method is based on protein precipitation and subsequent ultra-high performance liquid chromatography separation followed by tandem mass spectrometry detection. The mass spectrometric parameters for detection of TAK-438F, M-I, M-III and M-IV-Sul were modified from their optimum values in order to achieve a simultaneous quantification while retaining enough sensitivity and wide dynamic ranges for all the target analytes. The validity and robustness of the method was verified through a validation study as per the regulatory guidance on bioanalytical method validation. The calibration ranges are 0.1-100 ng/mL for TAK-438F and M-III, and 1-1000 ng/mL for M-I, M-II and M-IV-Sul using the 100 μL of human plasma. The total run time per sample is 5 min. The working solution for M-III was recommended to be prepared separately, especially for the long-term use, in order to avoid the instability of M-III in the mixed working solutions, which could cause the high consumption of reference standards. The established method was applied to clinical pharmacokinetic studies and concentrations of all the analytes in human plasma were successfully determined with high reproducibility ensured by incurred sample reanalysis, indicating the suitableness of the established method.
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address: tomoki.yoneyama@takeda.com.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yoneyama
authors.affiliation: Strategic CMC Planning, Chemistry Manufacturing and Control Center, Takeda Pharmaceutical Company Limited, 2-17-85, Juso-honmachi, Yodogawa-ku, Osaka 532-8686, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Teshima
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Jinno
authors.affiliation: Analytical Development Laboratories, Chemistry Manufacturing and Control Center, Takeda Pharmaceutical Company Limited, 2-17-85, Juso-honmachi, Yodogawa-ku, Osaka 532-8686, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Asahi
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D008297:Male; D011758:Pyrroles / Q000097:blood* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000097:blood* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C552956:1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; D011758:Pyrroles; D013449:Sulfonamides
keywords: Bioanalytical method validation (BMV); Human plasma; LC/MS/MS; Regulated bioanalysis; Simultaneous quantification; Vonoprazan (TAK-438F)