Publications (3)3.1 Total impact
Article: Study of aldehyde oxidase-catalyzed metabolic pathway of phenanthridine using MCR-ALS method.[show abstract] [hide abstract]
ABSTRACT: Evaluation of metabolic pathways is one of the challenging areas in biological and pharmaceutical sciences. Phenanthridine oxidation to phenanthridinone is used commonly to study aldehyde oxidase activity. This reaction could pass through phenanthridine N-oxide intermediate. In the present study, the application of multivariate curve resolution, optimized by alternating least squares (MCR-ALS) to investigate this metabolic pathway has been described. The results obtained from MCR-ALS analysis along with those obtained from the use of potassium ferrocyanide method indicated that phenanthridine is directly oxidized to phenanthridinone by rat liver aldehyde oxidase without passing through phenanthridine N-oxide intermediate. It was also found that the later compound is not metabolized by this enzyme.Bioprocess and Biosystems Engineering 02/2011; 34(2):173-7. · 1.81 Impact Factor
Article: Simultaneous Determination of 6-Mercaptopurine and its Oxidative Metabolites in Synthetic Solutions and Human Plasma using Spectrophotometric Multivariate Calibration Methods[show abstract] [hide abstract]
ABSTRACT: Introduction: 6-Mercaptopurine (6MP) is an important chemotherapeutic drug in the conventional treatment of childhood acute lymphoblastic leukemia (ALL). It is catabolized to 6-thiouric acid (6TUA) through 8-hydroxo-6-mercaptopurine (8OH6MP) or 6-thioxanthine (6TX) intermediates. Methods: High-performance liquid chromatography (HPLC) is usually used to determine the contents of therapeutic drugs, metabolites and other important biomedical analytes in biological samples. In the present study, the multivariate calibration methods, partial least squares (PLS-1) and principle component regression (PCR) have been developed and validated for the simultaneous determination of 6MP and its oxidative metabolites (6TUA, 8OH6MP and 6TX) without analyte separation in spiked human plasma. Mixtures of 6MP, 8-8OH6MP, 6TX and 6TUA have been resolved by PLS-1 and PCR to their UV spectra. Results: Recoveries (%) obtained for 6MP, 8-8OH6MP, 6TX and 6TUA were 94.5-97.5, 96.6-103.3, 95.1-96.9 and 93.4-95.8, respectively, using PLS-1 and 96.7-101.3, 96.2-98.8, 95.8-103.3 and 94.3-106.1, respectively, using PCR. The NAS (Net analyte signal) concept was used to calculate multivariate analytical figures of merit such as limit of detection (LOD), selectivity and sensitivity. The limit of detections for 6MP, 8-8OH6MP, 6TX and 6TUA were calculated to be 0.734, 0.439, 0.797 and 0.482 µmol L-1, respectively, using PLS and 0.724, 0.418, 0783 and 0.535 µmol L-1, respectively, using PCR. HPLC was also applied as a validation method for simultaneous determination of these thiopurines in the synthetic solutions and human plasma. Conclusion: Combination of spectroscopic techniques and chemometric methods (PLS and PCR) has provided a simple but powerful method for simultaneous analysis of multicomponent mixtures.BioImpacts. 01/2011; 1:53-62.
Article: Synthesis, characterization, and drug‐release behavior of novel PEGylated bovine serum albumin as a carrier for anticancer agents[show abstract] [hide abstract]
ABSTRACT: To develop a novel pH-sensitive PEGylated carrier for protein-based anticancer agents, we modified bovine serum albumin (BSA) with poly(ethylene glycol) citrate ester (PEG–CA) through amidation with its amino groups. Increasing the mixing ratio of albumin from 3 to 6 with respect to PEG–CA resulted in a 2-fold increase in the degree of albumin modification. Adriamycin (ADR)-loaded PEG–CA–BSA hydrogels and microparticles were prepared, and the cumulative amounts of ADR released from the PEG–CA–BSA hydrogels (phosphate-buffered saline, pH 7.4) showed that all the PEG-CA-BSA(x) (x represents degree of substitution of PEG to amino group of albumin, i.e. 26%, 28%, 31% and 49%) hydrogels had lower ADR release rates with a slight initial burst release. During the first 24 h, the cumulative releases were 15.5% for PEG–CA–BSA(49), 24% for PEG–CA–BSA(31), 31% for PEG–CA–BSA(28), and 38% for PEG–CA–BSA(26). Afterward, all the release rates slowed, and they were almost in the following order: PEG–CA–BSA(26) > PEG–CA–BSA(28) > PEG–CA–BSA(31) > PEG–CA–BSA(49). The release rates of ADR from the microparticles were dependent on the amount of glutaraldehyde. According to our findings, a higher PEG–CA/BSA molar ratio led to a reduced cumulative amount of ADR released from the hydrogels, whereas higher release rates were observed for microparticles with a lower amount of BSA in the conjugates in a pH-dependent manner. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011Journal of Applied Polymer Science 09/2010; 119(5):2635 - 2643. · 1.29 Impact Factor