Absolute oral bioavailability of fenofibric acid and choline fenofibrate in rats determined by ultra-performance liquid chromatography tandem mass spectrometry.
Choline fenofibrate is the choline salt of fenofibric acid, which releases free fenofibric acid in the gastrointestinal tract. To estimate the absolute oral bioavailability of fenofibric acid and choline fenofibrate, a novel and sensitive UPLC-MS/MS method with liquid-liquid extraction procedure was developed for the determination of fenofibric acid in rat plasma. The separation was achieved on a Phenomenex Kinetex C18column (50 × 2.1 mm, 2.6 μm) containing 2 mm ammonium acetate-methanol with a gradient elution program. Validations of this method including specificity, sensitivity (limit of quantification, 5 ng/mL), linearity (0.005-10 μg/mL), accuracy (within ±4.3%), precision (intra- and inter-day coefficient of variation <11.3%), recovery (94.9-105.2% for fenofibric acid), matrix effect, stability and dilution, were all within acceptable limits. This method successfully supported the determination of fenofibric acid and choline fenofibrate. The absolute oral bioavailability was 93.4% for choline fenofibrate and 40.0% for fenofibric acid. These results suggested that choline fenofibrate and fenofibric acid had a better in vivo pharmacokinetic behavior than that of fenofibrate. The two new orally administrated pharmaceuticals, fenofibric acid and choline fenofibrate, can be developed as alternatives to fenofibrate.
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Xudan
X
Wei
Chia Tai Tianqing Pharmaceutical Group Co. Ltd, Lianyungang, China.
Ping
P
Li
Dalian Huirui Pharmaceutical Co. Ltd, Dalian, China.
Meina
M
Liu
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Yuqian
Y
Du
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Menglin
M
Wang
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Jinling
J
Zhang
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Jing
J
Wang
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Hongzhuo
H
Liu
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Xiaohong
X
Liu
D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002794:Choline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D011345:Fenofibrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006207:Half-Life; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction / Q000379:methods; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
C006012:fenofibric acid; D002794:Choline; D011345:Fenofibrate
UPLC-MS/MS; absolute oral bioavailability; choline fenofibrate; fenofibric acid; liquid-liquid extraction