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Modulation of rat P-gp by multiple doses of Naoxintong capsule using fexofenadine as a phenotyping probe
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DOI   10.11656/j.issn.1672-1519.2018.01.12
Key Words   LC-MS/MS;fexofenadine;Naoxintong;P-gp
Author NameAffiliationE-mail
OUYANG Huizi The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China  
LIU Huaming Tianjin State Key Laboratory of Modern Chinese Medicine-Province and Ministry co-established State Key Laboratory Cultivation Base, Tianjin 300193, China  
WANG Xingrui Tianjin State Key Laboratory of Modern Chinese Medicine-Province and Ministry co-established State Key Laboratory Cultivation Base, Tianjin 300193, China  
CHANG Yanxu Tianjin State Key Laboratory of Modern Chinese Medicine-Province and Ministry co-established State Key Laboratory Cultivation Base, Tianjin 300193, China  
HE Jun Tianjin State Key Laboratory of Modern Chinese Medicine-Province and Ministry co-established State Key Laboratory Cultivation Base, Tianjin 300193, China hejun673@163.com 
Abstract
    [Objective] A liquid chromatography tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination of fexofenadine in rats plasma, and the effects of Naoxintong on P-gp in rats were studied.[Methods] The samples were separated on a Waters XBridgeTM C18 column (2.1 mm×100 mm, 3.5 μm) with a gradient mobile phase system of 0.1% (V/V) formic acid and acetonitrile. Fexofenadine and diphenhydramine (Internal Standard) were detected by electrospray ionization (ESI) with multiple reaction monitoring. The transitions at m/z 502.3 → 466.3 (fexofenadine), and m/z 256.1 → 166.9 (IS), respectively.[Results] A good linear response was observed over the concentration ranges of 1-250 ng/mL. Both intra and inter-day precision (RSD) were within 8.7%, and the extraction recovery were more than 83.0%.[Conclusion] The results suggested that the method proved to be highly reproducible and sensitive that was successfully applied in the pharmacokinetic study of fexofenadine, and the inhibitory effect of Naoxintong capsule on the activity of P-gp in rats after continuous administration of Naoxintong were observed.

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