Simultaneous determination of fimasartan, a novel antihypertensive agent, and its active metabolite in rat plasma by liquid chromatography-tandem mass spectrometry.
Fimasartan, 2-butyl-5-dimethylaminothiocarbonylmethyl-6-methyl-3-[[2'-(1H tetrazol -5-yl)biphenyl-4-yl]methyl]pyrimidin-4(3H)-one (BR-A-657), is a novel angiotensin II receptor blocker exhibiting potent and selective AT1 receptor blocking activity. This study reports the liquid chromatography-tandem mass spectrometry assay for the simultaneous determination of fimasartan and its active metabolite, BR-A-557, in rat plasma. The assay was validated to demonstrate the specificity, linearity, recovery, lower limit of quantification, accuracy, precision and stability. The multiple reaction monitoring was based on the transition of m/z 502.1 → 207.1 for fimasartan, 486.2 → 207.1 for BR-A-557 and 526.1 → 207.1 for BR-A-563 (internal standard). The assay utilized a simple precipitation procedure with acetonitrile and isocratic elution. The LLOQ was 0.2 ng/mL for fimasartan and BR-A-557 using 50 μL plasma samples. The assay was linear over a concentration range from 0.2 to 500 ng/mL for fimasartan and BR-A-557, with correlation coefficients >0.9995. The intra- and inter-day assay accuracies were 93.6-108.0 and 90.8-101.4% for fimasartan and 102.2-107.1 and 99.6-103.3% for BR-A-557, respectively. The intra- and inter-day precision were 2.4-4.4 and 3.0-13.4% for fimasartan and 3.1-5.2 and 2.8-9.8% for BR-A-557, respectively. The developed assay may be used to study the metabolism and mechanistic pharmacokinetics of fimasartan in future studies.
College of Pharmacy, Catholic University of Daegu, Gyeongsan, Gyeongbuk, Korea.
Beom Soo
BS
Shin
Tae Hwan
TH
Kim
Soo Heui
SH
Paik
Yong Ha
YH
Chi
Joo Han
JH
Lee
Hyun Kwang
HK
Tan
Yohan
Y
Choi
Minki
M
Kim
Sun Dong
SD
Yoo
D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood* / Q000737:chemistry; D001713:Biphenyl Compounds / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D016014:Linear Models; D008297:Male; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013777:Tetrazoles / Q000097:blood* / Q000737:chemistry
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D011743:Pyrimidines; D013777:Tetrazoles; C558933:fimasartan