A highly sensitive and rapid LC-MS/MS method for quantification of bexarotene in mouse plasma and brain tissue: Application to mice pharmacokinetic study.
J Chromatogr B Analyt Technol Biomed Life Sci
; 1189: 123025, 2022 Jan 15.
Article
in En
| MEDLINE
| ID: mdl-34840083
ABSTRACT
Emerging evidence has suggested that bexarotene, a nearly 20-year-old skin cancer drug, may be a potential drug candidate to treat Alzheimer's disease (AD) and other neurodegenerative disorders. As described in this study, a highly sensitive and rapid method, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine bexarotene in mouse plasma and brain tissue, was established and validated for the first time. Single-step protein precipitation utilizing methanol solution (containing 0.05 % acetic acid) as precipitation agent was employed to prepare the samples of plasma and brain tissue. Chromatographic separation in gradient elution mode was conducted via an Agilent ZORBAX SB-C18 column (50 mm × 4.6 mm, 5 µm) employing methanol-ammonium acetate buffer (5 mM, pH adjusted to 4.6 with acetic acid) as mobile phase which flowed at 0.45 mL/min. The total run time was 6 min for each sample. Detection through mass spectrometric technique was operated by selected reaction monitoring (SRM) in negative electrospray ionization mode. The method was linear within the range of 10.0-15000 ng/mL for plasma and 10.0-600 ng/mL for brain tissue homogenate with the lower limit of quantification of 10.0 ng/ml. The plasma or tissue homogenate was only required 20 µL. The intra- and inter-day precision were less than 13.8 %, and the RE was between -7.4 % and 3.4 %. The method was applied to investigate the plasma pharmacokinetics and brain distribution of bexarotene in mice after being intragastrically administered with bexarotene at the dosage of 100 mg/kg. The results showed that both brain and plasma concentrations of bexarotene peaked at 1.0 h. Bexarotene was rapidly eliminated with a half-life of 2.0 h.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Chemistry
/
Chromatography, Liquid
/
Tandem Mass Spectrometry
/
Bexarotene
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Chromatogr B Analyt Technol Biomed Life Sci
Year:
2022
Document type:
Article