Permeability and transport mechanism of trihexyphenidyl hydrochloride in Caco-2 cell monolayer model with a validated UPLC-MS/MS method
| Autor: | Yang Lu, Ning Li, Chengcan Lu, Di Zhao, Kejia Fu, Jiali Wei, Jing Zhou, Xijing Chen, Kangna Cao, Yongjie Zhang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Formic acid
Hydrochloride Coefficient of variation Clinical Biochemistry Pharmaceutical Science Mass spectrometry 01 natural sciences Glycosphingolipids Permeability Analytical Chemistry chemistry.chemical_compound Limit of Detection Tandem Mass Spectrometry Cell Line Tumor Drug Discovery Monolayer Humans Spectroscopy Chromatography High Pressure Liquid Trihexyphenidyl Hydrochloride Chromatography 010405 organic chemistry Chemistry 010401 analytical chemistry Reproducibility of Results Membrane transport 0104 chemical sciences Trihexyphenidyl Methanol Caco-2 Cells |
| Zdroj: | Journal of pharmaceutical and biomedical analysis. 178 |
| ISSN: | 1873-264X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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