Validated UPLC-MS/MS method for determination of moclobemide in human brain cell supernatant and its application to bidirectional transport study.

A simple and sensitive analytical method based on ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for determination of moclobemide in human brain cell monolayer as an in vitro model of blood-brain barrier. Brucine was employed as the internal standard. Moclobemide and internal standard were extracted from cell supernatant by ethyl acetate after alkalinizing with sodium hydroxide. The UPLC separation was performed on an Acquity UPLC(TM) BEH C18 column (50 × 2.1 mm, 1.7 µm, Waters, USA) with a mobile phase consisting of methanol-water (29.5:70.5, v/v); the water in the mobile phase contained 0.05% ammonium acetate and 0.1% formic acid. Detection of the analytes was achieved using positive ion electrospray via multiple reaction monitoring mode. The mass transitions were m/z 269.16 → 182.01 for moclobemide and m/z 395.24 → 324.15 for brucine. The extraction recovery was 83.0-83.4% and the lower limit of quantitation (LLOQ) was 1.0 ng/mL for moclobemide. The method was validated from LLOQ to 1980 ng/mL with a coefficient of determination greater than 0.999. Intra- and inter-day accuracies of the method at three concentrations ranged from 89.1 to 100.9% for moclobemide with precision of 1.1-9.6%. This validated method was successfully applied to bidirectional transport study of moclobemide blood-brain barrier permeability.

Quantitative analysis of trazodone in human plasma by using HPLC-fluorescence detector coupled with strong cation exchange chromatographic column: application to a pharmacokinetic study in Chinese healthy volunteers.

A simple, selective, and sensitive high performance liquid chromatography (HPLC) procedure has been developed for determination of trazodone in human plasma. Prazosin was employed as the internal standard (IS). Sample preparation involved liquid-liquid extraction by methyl tert-butyl ether after alkalinization with ammonia. The HPLC separation was performed on a CAPCELL PAK SCX column (250mm×4.6mm, 5.0µm, Shiseido, Japan) with a mobile phase of acetonitrile/80mmol/L ammonium phosphate (pH adjusted to 6.0) (60:40, v/v) at a flow rate of 1.2mL/min. The peaks were detected by using fluorescence detector (excitation wavelength 320nm and emission wavelength 440nm). The extraction recovery was 72.6-88.3% and the method was over the concentration range of 5.0-2486ng/mL with a lower limit of quantitation (LLOQ) of 5.0ng/mL using 300µL of plasma. The intra- and inter-day accuracy of the method at three concentrations ranged from 96.7% to 104.2% for trazodone with precision of 2.9-3.7%. This validated method was successfully applied to a pharmacokinetic study enrolling 12 Chinese volunteers administered a single oral trazodone hydrochloride extended-release tablet of 75mg.

Progress on mechanism of Tripterygium wilfordii-induced liver injury and detoxification mechanism of licorice / 中国中药杂志

Tripterygium wilfordii has exihibited multiple pharmacological activities, such as anti-inflammatory, immune modulation, anti-tumor and anti-fertility. T. wilfordii have been used for the therapy of inflammation and autoimmune diseases including rheumatoid arthritis, immune complex nephritis and systemic lupus erythematosus clinically. However, it is well known that T. wilfordii has small margin between the therapeutic and toxic doses and could cause serious injury on digestive, reproductive and urogenital systems. Among all the organs, liver is one of the most remarkable targets of T. wilfordii-induced toxicities, and the damage is more serious than others. It is generally accepted that T. wilfordii-induced liver injury is a result of the combined effects of toxic elements of T. wilfordii. It is reported in several studies that the mechanism of T. wilfordii-induced liver injury may be related to lipid peroxidation, cell apoptosis and immune damage, and so on. Licorice is one of the most commonly used Chinese herbal medicine, with effects of heat- clearing and detoxicating, anti-inflammatory and hepatoprotective, reconciling various drugs, and so on. Licorice often accompany T. wilfordii in clinical application which can significantly reduce the liver injury induced by T. wilfordii. The attenuated effect is exact, but the mechanism is still a lack of in-depth study. This paper reviews the studies on T. wilfordii-induced liver injury and the related mechanism as well as licorice and other traditional Chinese medicine accompany T. wilfordii to reduce the injury in recent years, so as to provide reference for related research in the future.