title: Characterization of fimasartan metabolites in human liver microsomes and human plasma.
abstract: 1. The metabolites of fimasartan (FMS), a new angiotensin II receptor antagonist, were characterized in human liver microsomes (HLM) and human subjects. 2. We developed a method for a simultaneous quantitative and qualitative analysis using predictive multiple reaction monitoring information-dependent acquisition-enhanced product ion scanning. To characterize metabolic reactions, FMS metabolites were analyzed using quadrupole-time of flight mass spectrometer in full-scan mode. 3. The structures of metabolites were confirmed by comparison of chromatographic retention times and mass spectra with those of authentic metabolite standards. 4. In the cofactor-dependent microsomal metabolism study, the half-lives of FMS were 56.7, 247.9 and 53.3 min in the presence of NADPH, UDPGA and NADPH + UDPGA, respectively. 5. The main metabolic routes in HLM were S-oxidation, oxidative desulfuration, n-butyl hydroxylation and N-glucuronidation. 6. In humans orally administered with 120 mg FMS daily for 7 days, the prominent metabolites were FMS S-oxide and FMS N-glucuronide in the 0-8-h pooled plasma sample of each subject. 7. This study characterizes, for the first time, the metabolites of FMS in humans to provide information for its safe use in clinical medicine.
authors.affiliation: a College of Pharmacy, Chungnam National University , Daejeon , Republic of Korea .
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: a College of Pharmacy, Chungnam National University , Daejeon , Republic of Korea .
authors.forename: Young Jae
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: b Bio-Evaluation Center, KRIBB , Ochang , Chungbuk , Republic of Korea .
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: c Central Research Institute, Boryung Pharm. Co., Ltd. , Ansan , Gyeonggi , Republic of Korea .
authors.forename: Yong Ha
authors.initials: YH
authors.lastname: Chi
authors.affiliation: c Central Research Institute, Boryung Pharm. Co., Ltd. , Ansan , Gyeonggi , Republic of Korea .
authors.forename: Soo Heui
authors.initials: SH
authors.lastname: Paik
authors.affiliation: d College of Pharmacy, Korea University , Jochiwon-eup , Sejong , Republic of Korea .
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: e College of Pharmacy and Medicinal Research Center (MRC), Chungbuk National University , Seowon-gu, Cheungju , Chungbuk , Republic of Korea .
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Jung
authors.affiliation: a College of Pharmacy, Chungnam National University , Daejeon , Republic of Korea .
authors.forename: Chang Seon
authors.initials: CS
authors.lastname: Ryu
authors.affiliation: f AB SCIEX, Yangjae 2-Dong Seocho-Gu , Seoul , Republic of Korea .
authors.forename: Kwon-Bok
authors.initials: KB
authors.lastname: Kim
authors.affiliation: g Department of Pharmacology and PharmacoGenomics Research Center , Inje University College of Medicine , Busan , Republic of Korea , and.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: h Department of Biomedical Science and Clinical Trial Center, BK21 PLUS , KNU Bio-Medical Convergence Program for Creative Talent, Kyungpook National University Graduates School and Hospital , Daegu , Republic of Korea.
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Yoon
authors.affiliation: a College of Pharmacy, Chungnam National University , Daejeon , Republic of Korea .
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000328:Adult; D001713:Biphenyl Compounds / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization; D013777:Tetrazoles / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001713:Biphenyl Compounds; D011743:Pyrimidines; D013777:Tetrazoles; D009249:NADP; C558933:fimasartan
keywords: Fimasartan; metabolic stability; metabolite identification; qualitative and quantitative analysis