A sensitive and reliable high-performance liquid chromatographic (HPLC) method, using a solid-phase extraction (SPE), was developed and validated for determination of leucovorin (LV) in human plasma. Plasma sample was extracted by using a Sep-Pak cartridge which could be renewable. The sample was analyzed by HPLC with UV detection at 286 nm. The method was shown to perform selectively and sensitively for LV. The main metabolite of LV, 5-methyltetrahydrofolic acid, and endogenous substances in plasma did not show any interference in the analysis. The limit of detection was 10 ng/mL for LV in plasma and the linear range was 50-1500 ng/mL in plasma. The relative standard deviation (RSD) of intra-day and inter-day assays was 2.8-6.1% and 2.4-5.3%, respectively. The extraction recoveries of LV in plasma were over 90%. The method was proved to be applicable to the pharmacokinetic study of LV in healthy volunteers after a single oral administration (75 mg). The pharmacokinetic parameters and relative bioavailability were investigated for domestic LV tablet and capsule vs an imported tablet.

A simple and sensitive method for the simultaneous determination of eight parabens in human plasma and urine samples was developed. The samples were preconcentrated using dispersive liquid-liquid microextraction based on the solidification of floating organic drops and determined by high-performance liquid chromatography with ultraviolet detection. The influence of variables affecting the extraction efficiency was investigated and optimized using Placket-Burman design and Box-Behnken design. The optimized values were: 58 μL of 1-decanol (as extraction solvent), 0.65 mL methanol (as disperser solvent), 1.5% w/v NaCl in 5.0 mL of sample solution, pH 10.6, and 4.0 min centrifugation at 4000 rpm. The extract was injected into the high-performance liquid chromatography system for analysis. Under the optimum conditions, the linear ranges for eight parabens in plasma and urine were 1.0-1000 ng/mL, with correlation coefficients above 0.994. The limit of detection was 0.2-0.4 and 0.1-0.4 ng/mL for plasma and urine samples, respectively. Relative recoveries were between 80.3 and 110.7%, while relative standard deviations were less than 5.4%. Finally, the method was applied to analyze the parabens in 98 patients of primary breast cancer. Results showed that parabens existed widely, at least one paraben detected in 96.9% (95/98) of plasma samples and 98.0% (96/98) of urine samples.

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The development of therapeutic biosimilar antibodies has become an important driving force of the modern biopharmaceutical industry. In this study, physiochemical characteristics (amino acid sequence, intact/subunit molecular weight, isoelectric point, post-translation modification, and disulfide linkage pattern), purity (charge variants, high and low molecular weight variants), antigen binding activity, Fc receptor binding affinity and Fc-effector function (CDC and ADCC) were analyzed by using an extensive set of state-of-the-art and orthogonal analytical technologies to provide a comprehensive characterization of the innovative product rituximab and two biosimilar candidates. The similarity study showed that biosimilar candidate 1 (BC1) and the reference product (RP) MabThera had an identical protein amino acid sequences and highly similar primary structures along with similar purity, heterogeneity profiles, antigen binding activity, Fc receptor binding affinity, and Fc-effector functions. Biosimilar candidate 2 (BC2), which had an amino acid replacement at a constant region, a different N-glycosylation profiling, and purity, was not analytically similar to RP. Although BC2 showed improvement such as an increased level of afucose, another IgG1 allotype, and similar biological activities, it was not recommended to be applied as a biosimilar compound in drug registration because the biosimilar manufacturer must first show that its primary structure was identical to that of RP. Our physicochemical characterizations and bioassay comparability study provided a deepened understanding of the structure–function relationship of quality attributes.

In this paper, we propose a new strategy to enhance the photoelectric performance of ultraviolet (UV) photodetectors by exploiting a synergistic photo-thermal effect which is induced by a localized surface...