Abstract：
:A rapid and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was applied to investigate the permeability characteristics and transport mechanism of trihexyphenidyl hydrochloride (TH) in D-hanks with the Caco-2 cells model. Analytes were separated using an Zorbax Extend-Agilent C18 (1.8 μm, 4.6 × 30 mm) column following a simple methanol precipitation treatment. The mobile phase consisted of methanol and water containing 0.1% formic acid, and the total gradient program time was 1.5 min. Method validation results showed TH was linear in 2-500 ng/mL (r2 > 0.99), and the lower limit of quantification (LLOQ) was 2 μg/mL. The intra-run and inter-run precision (coefficient of variation, CV) was within 2.80%, and the accuracy (relative error, RE) was within ±11.10%. Stability of TH was evaluated in different storage conditions, including short-term I-III, long-term I-III, 2 and 4 h in the artificial gastrointestinal tract, respectively. There was no obvious interference between TH and internal standards (IS). With the established Caco-2 monolayer permeability model, Papp(AB) of TH was calculated as 46.29 ± 8.31 × 10-6 cm/s, and the efflux ratio (ER) value was calculated as 0.22, indicating a high permeability character of TH. The transmembrane transport of TH followed the concentration-dependent, temperature-independent, and energy-free manner. Collectively, these characteristics indicate that TH is a highly permeable drug and the transport mechanism is mainly via passive diffusion.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Lu C,Fu K,Cao K,Wei J,Zhou J,Zhao D,Li N,Lu Y,Chen X,Zhang Ydoi
10.1016/j.jpba.2019.112924subject
Has Abstractpub_date
2020-01-30 00:00:00pages
112924eissn
0731-7085issn
1873-264Xpii
S0731-7085(19)31614-0journal_volume
178pub_type
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