UHPLC-MS/MS Determination, Pharmacokinetic, and Bioavailability Study of Taxifolin in Rat Plasma after Oral Administration of its Nanodispersion

Molecules

Ming-Jie Gao¹  Chun-Juan Yang¹  Bing-You Yang²  Jin-Nan Lv²  Yong-Hai Meng²  Zhi-Bin Wang²  Hai-Xue Kuang²  Ying-Ying Mi² 

[1] College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, Heilongjang, China;Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjang, China;

关键词: taxifolin;    UHPLC-MS/MS;    nanodispersion;    ratplasma;    pharmacokinetics;   

DOI  :  10.3390/molecules21040494

来源: DOAJ

【 摘 要 】

A rapid and sensitive LC-MS/MS method based on the Triple Quad system has been developed and validated for the determination and pharmacokinetics of taxifolin and its nanodispersion in rat plasma. Taxifolin plasma samples along with butylparaben (internal standard) were pre-treated by liquid-liquid extraction with ethyl acetate, and then separated on a SB-C18 RRHD column (150 mm × 2.1 mm × 1.8 μm) using isocratic elution with a run time of 3.0 min. The mobile phase was acetonitrile–water (90:10, v/v) containing 5 mM ammonium acetate at a flow rate of 0.4 mL/min. Quantification of taxifolin was performed by the electrospray ionization tandem mass spectrometry in the multiple reaction monitoring (MRM) mode with negative atmospheric ionization at m/z 303.0→285.0 for taxifolin and 193.1→92.0 for I.S., respectively. The calibration curve of taxifolin showed good linearity over a concentration range of 5.0–4280 ng/mL with a correlation coefficient of 0.9995. The limit of quantification (LLOQ) was 5.0 ng/mL. Intra-day, inter-day precision and accuracy (percent relative to standard deviation) were all within 8% at three concentration levels. A total recovery of taxifolin and I.S. was beyond 75%. The present LC-MS/MS method was successfully applied to pharmacokinetic studies of taxifolin after intravenous administration of taxifolin, oral administration of its physical mixture and nanodispersion. The absolute bioavailability of taxifolin was calculated as 0.75% for taxifolin nanodispersion and 0.49% for taxifolin, respectively.

【 授权许可】

Unknown