Lee Y.,Hanyang University |
Kim J.,Hanyang University |
Lee S.,Hanyang University |
Woo Y.-A.,Korea United Pharm. Inc. |
Chung H.,Hanyang University
Talanta | Year: 2012
Direct transmission Raman measurements for analysis of pharmaceuticals in capsules are advantageous since they can be used to determine active pharmaceutical ingredient (API) concentrations in a non-destructive manner and with much less fluorescence background interference from the capsules themselves compared to conventional back-scattering measurements. If a single calibration model such as developed from spectra simply collected in glass vials could be used to determine API concentrations of samples contained in capsules of different colors rather than constructing individual models for each capsule color, the utility of transmission measurements would be further enhanced. To evaluate the feasibility, transmission Raman spectra of binary mixtures of ambroxol and lactose were collected in a glass vial and a partial least squares (PLS) model for the determination of ambroxol concentration was developed. Then, the model was directly applied to determine ambroxol concentrations of samples contained in capsules of 4 different colors (blue, green, white and yellow). Although the prediction performance was slightly degraded when the samples were placed in blue or green capsules, due to the presence of weak fluorescence, accurate determination of ambroxol was generally achieved in all cases. The prediction accuracy was also investigated when the thickness of the capsule was varied. © 2011 Elsevier B.V. All rights reserved.
Lee J.-H.,Korea Institute of Toxicology |
Chae Y.-J.,Seoul National University |
Lee K.-R.,Korea Research Institute of Chemical Technology |
Ahn S.-H.,Korea Research Institute of Chemical Technology |
And 7 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2012
FK-3000 can inhibit proliferation of carcinomas and arrest the growth of carcinoma cells through cytotoxic (apoptosis induction) and cytostatic (cell cycle arrest) effects. A rapid and sensitive assay was developed and validated using liquid chromatography-mass spectrometry (LC-MS) for FK-3000 in rat plasma. FK-3000 was extracted with ethyl acetate from rat plasma samples, and the residue containing the FK-3000 was dried in a gentle stream of nitrogen and reconstituted with acetonitrile. The FK-3000 was quantified using high-performance liquid chromatography (HPLC; Waters Alliance 2695) with a reversed phase Gemini column (3. mm × 150. mm, 5μm; Phenomenex, USA) and a Waters Micromass ZQ detector. FK-3000 and phenazine, an internal standard (IS), were analyzed by selected ion monitoring (SIM) at m/z transitions of 418.45 and 256, respectively. A lower limit of quantification (LLOQ) of 10. ng/mL was observed, with a linear dynamic range from 10 to 10,000. ng/mL (R>0.999). The accuracy, precision, recovery, matrix effects, and stability of the assay were deemed acceptable according to the FDA guidance for industry (bioanalytical method validation). The FK-3000 concentration was measured in plasma samples up to 6. h following FK-3000 administration at an oral dose of 20. mg/kg. The findings indicate that the assay method is suitable for routine pharmacokinetic (PK) studies of FK-3000 in rats. © 2012 Elsevier B.V.
Lee J.-H.,Korea Institute of Toxicology |
Lim H.,Korea Institute of Toxicology |
Kim D.-G.,Korea Institute of Toxicology |
Park D.-H.,Korea Institute of Toxicology |
And 6 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011
An assay method for the determination of oltipraz, a candidate drug for the treatment of liver fibrosis and liver cirrhosis, was developed in rat plasma using a fast-flow protein precipitation (FF-PPT) method coupled with LC-MS/MS for quantification to reduce the labor and to improve the speed of analysis. The applicability of the assay to pharmacokinetic studies was also evaluated. Oltipraz and ethyl-oltipraz, an internal standard (IS), were analyzed by multiple reaction monitoring (MRM) at m/. z transitions of 227. →. 193 and 241. →. 174, respectively. A lower limit of quantification (LLOQ) of 20 ng/mL was observed, with a linear dynamic range from 20 to 4000 ng/mL (R>. 0.997). The accuracy, precision, dilution, recovery, and stability of the assay were deemed acceptable according to FDA guidelines. Oltipraz concentrations were measured successfully in plasma samples up to 12 h post-dose in rats that had received an oral dose of 60 mg/kg. The findings indicate that the assay method is rapid and sensitive to oltipraz, showing applicability for pharmacokinetics (PK) studies of oltipraz in other small animals, including rats. © 2011 Elsevier B.V.
Thao L.Q.,Sungkyunkwan University |
Byeon H.J.,Sungkyunkwan University |
Lee C.,Sungkyunkwan University |
Lee S.,Sungkyunkwan University |
And 6 more authors.
Pharmaceutical Research | Year: 2016
Purpose: We developed a new nanoparticle formulation comprised of human serum albumin (HSA) for co-delivery of doxorubicin (Dox) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with the goal of apoptotic synergy in the treatment of colon cancer. Methods: TRAIL (0.2, 0.4, 1.0%)- and Dox-loaded HSA nanoparticles (TRAIL/Dox HSA NPs) were prepared by using the nabTM technology. Morphological and physicochemical characterizations were investigated by dynamic light scattering and transmission electron microscopy. Synergistic cytotoxicity, apoptotic activity, and potential penetration into mass tumor were determined in HCT116 cell-based systems. Furthermore, antitumor efficacy and tumor targeting were also investigated. Results: TRAIL/Dox HSA NPs were uniformly spherical with sizes of 60 ∼ 120 nm. The encapsulation efficacy of Dox and TRAIL was 68.9-77.2% and 80.4-86.0%, respectively. TRAIL 1.0%/Dox HSA NPs displayed the best inhibition of HCT116 colon cancer cells; inhibition was 6 times higher than achieved with Dox HSA NPs. The TRAIL 1.0%/Dox HSA NPs formulation was studied further. Flow cytometry analysis and TUNEL assay revealed that TRAIL 1.0%/Dox HSA NPs had markedly greater apoptotic activity than Dox HSA NPs. In HCT116 tumor-bearing BALB/c nu/nu mice, TRAIL 1.0%/Dox HSA NPs had significantly higher antitumor efficacy than Dox HSA NPs (tumor volume; 933.4 mm3 vs. 3183.7 mm3, respectively). TRAIL 1.0%/Dox HSA NPs penetrated deeply into tumor masses in a HCT116 spheroid model and localized in tumor sites after tail vein injection. Conclusions: Data indicate that TRAIL 1.0%/Dox HSA NPs offer advantages of co-delivery of Dox and TRAIL in tumors, with potential synergistic apoptosis-based anticancer therapy. © 2015 Springer Science+Business Media.