title: Validated LC-MS/MS Assay for the Quantitative Determination of Fimasartan in Human Plasma: Application to Pharmacokinetic Studies.
abstract: A simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of a newly developed antihypertensive agent fimasartan (BR-A657, Kanarb(®)) in human plasma was developed and validated. Fimasartan and internal standard (IS, BR-A563) were extracted by simple protein precipitation using acetonitrile and separated on a Phenyl-Hexyl column (Luna(®), 5 µm, 50 mm × 2.0 mm, Phenomenex) under the gradient conditions of mobile phase A (distilled water with 0.1% formic acid) and mobile phase B (100% acetonitrile with 0.1% formic acid) at a flow rate of 0.25 mL/min. Detection and quantification were performed by the mass spectrometer using multiple reaction monitoring mode at m/z 500.2 → 221.2 for fimasartan and m/z 524.3 → 204.9 for the IS. The assay was linear over a calibration range of 0.5-500 ng/mL with a lower limit of quantification of 0.5 ng/mL. The coefficient of variation of this assay precision was <14.9% and the accuracy exceeded 91.9%. This method provided the necessary sensitivity, linearity, precision, accuracy and specificity to allow the determination of fimasartan after oral administration to healthy Korean male volunteers in several drug-drug interaction studies conducted at the Clinical Trials Center of Seoul National University Hospital.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Seo Hyun
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Seul
authors.initials: S
authors.lastname: Oh
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Hwa Suk
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: SoJeong
authors.initials: S
authors.lastname: Yi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea joocho@snu.ac.kr.
authors.forename: Joo-Youn
authors.initials: JY
authors.lastname: Cho
mesh_terms: D001713:Biphenyl Compounds / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D016014:Linear Models; D008297:Male; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013777:Tetrazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D001713:Biphenyl Compounds; D011743:Pyrimidines; D013777:Tetrazoles; C558933:fimasartan