[Pharmacokinetics of 11 active components of Psoraleae Fructus in normal and diabetic rats].

A total of 11 active ingredients including psoralen, isopsoralen, bakuchiol, bavachalcone, bavachinin, corylin, coryfolin, isobavachalcone, neobavaisoflavone, bakuchalcone, and corylifol A from Psoraleae Fructus in the plasma samples of diabetic and normal rats were simultaneously determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated to elucidate the pharmacokinetic profiles of coumarins, flavonoids, and monoterpene phenols in normal and diabetic rats. The rat model of type 2 diabetes mellitus(T2DM) was induced by a high-sugar and high-fat diet combined with injection of 1% streptozotocin every two days. The plasma samples were collected at different time points after the rats were administrated with Psoraleae Fructus. The proteins in the plasma samples were precipitated by ethyl acetate, and the plasma concentrations of the 11 components of Psoraleae Fructus were determined by UHPLC-MS/MS. The pharmacokinetic parameters were calculated by DAS 3.0. The results showed that the pharmacokinetic beha-viors of 8 components including psoralen, isopsoralen, bakuchiol, and bavachinin from Psoraleae Fructus in both female and male mo-del rats were significantly different from those in normal rats. Among them, the coumarins including psoralen, isopsoralen, and corylin showed lowered levels in the blood of both female and male model rats. The flavonoids(bavachinin, corylifol A, and bakuchalcone) and the monoterpene phenol bakuchiol showed decreased levels in the female model rats but elevated levels in the male model rats. It is suggested that the dosage of Psoraleae Fructus should be reasonably adjusted for the patients of different genders at the time of clinical administration.

Simultaneous characterization of multiple Psoraleae Fructus bioactive compounds in rat plasma by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry for application in sex-related differences in pharmacokinetics.

A method for the simultaneous quantification of 13 bioactive compounds (psoralen, isopsoralen, isobavachin, bakuchalcone, neobabaisoflavone, bavachin, corylin, psoralidin, isobavachalcone, bavachinin, corylifol A, bavachalcone, and bakuchiol) by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry has been developed and validated in rat plasma. Osthol was used as an internal standard and plasma samples were pretreated with one-step liquid-liquid extraction. These analytes were separated using a gradient mobile phase system of water and acetonitrile at a flow rate of 0.2 mL/min on a reverse-phase C18 column and analyzed in the selected multiple reactions monitoring mode. All calibration curves were linear (r > 0.9952) over the tested ranges. The intra- and interday accuracy and precisions of these analytes at three different concentration levels were within the acceptable limits of <15% at all concentrations. The mean recoveries of these analytes at three concentrations were more than 60.2% and the matrix effects were in the range of 85-115%. Stability studies proved that the analytes were stable under the tested conditions. The developed method was applied to evaluating the pharmacokinetic study of 13 bioactive compounds after oral administration of Psoraleae Fructus in rat of different genders. Some active compounds in Psoraleae Fructus had sex-related pharmacokinetics.

Study on pharmacokinetics of eight active compounds from Bufei-Huoxue Capsule based on UHPLC-MS/MS.

Bufei-Huoxue Capsule (BFHX) was applied to treat chronic obstructive pulmonary disease (COPD) in China. It is composed of Astragali Radix, Paeoniae Radix Rubra, and Psoralea Fructus. A sensitive and reliable ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method was developed and validated to quantify the eight main bioactive compounds (psoralen, isopsoralen, neobabaisoflavone, corylin, bavachin, astragaloside IV, ononin and formononetin) in rat plasma after oral administration of BFHX. Osthol was used as an internal standard (IS). Plasma samples were pretreated with methanol to precipitate protein. Chromatographic separation was accomplished using Hypersil GOLDTM C18 column (2.1 mm × 100 mm, 1.9 µm) with a gradient elution profile and a mobile phase consisting of (A) 0.1% formic acid in water and (B) acetonitrile and the flow rate was set at 0.2 mL/min. Multiple reaction monitoring (MRM) mode was applied to perform mass spectrometric analyses. All calibration curves were linear (r > 0.9908) in tested ranges. The intra- and inter-day accuracy and precisions of eight compounds at three different concentration levels were within the acceptable limits. The extraction recovery was within the range of 76.4 âˆ¼ 105.2% and the matrix effects were within the range of 88.3 âˆ¼ 115.0% (RSD ≤ 15.6%). The dilution effects were within the range of 90.2 âˆ¼ 114.9%. These 8 compounds were stable under the tested conditions. So the developed method was valid to evaluate the pharmacokinetic study of eight bioactive compounds after oral administration of BFHX.

Development and validation of a sensitive UHPLC-MS/MS method for the measurement of ß-elemonic acid in rat plasma and tissues and its application to pharmacokinetics and tissue distribution study.

ß-Elemonic acid is one of the main active ingredients isolated from Boswellia carterii Birdw. which has been reported to exhibit potential anti-inflammatory and anti-cancer activities. There is few information about pharmacokinetics and tissue distribution of ß-elemonic acid by now. In this study, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) method has been developed and validated to determine ß-elemonic acid in rat plasma and various tissues after intragastric administration. Oleanolic acid was chosen as an internal standard (IS) and the plasma/tissue samples were pretreated with one-step liquid-liquid extraction. Chromatographic separation was accomplished on Eclipse Plus C18 analytical column (2.1 × 50 mm, 1.8 µm) utilizing a gradient mobile phase system consisting of water (with 0.1% ammonia-solution) and acetonitrile. ß-Elemonic acid and IS were detected and quantified using negative electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 453.3 â†’ 423.5 for ß-elemonic acid and m/z 455.3 â†’ 407.6 for IS. ß-Elemonic acid showed good linearity over the investigated concentration range (r > 0.9934) in rat plasma and tissue sample. The method was successfully applied for determination of ß-elemonic acid in bio-samples. A bimodal phenomenon appeared in the plasma concentration-time curve of the ß-elemonic acid. The highest tissue concentrations were found in the intestine including jejunum, ileum and colon.

Photocatalytic Degradation of Rhodamine B Under Visible Light Irradiation by TiO2 Doped Layered Zirconium Phosphates.

TiO2 doped layered zirconium phosphates were prepared by the hydrofluoric acid (HF) method and its photocatalytic performance was investigated in this study. Through the introduction of octylamine which acts as the intercalation and exfoliation reagent in the process, TiO2 could be uniformly generated and dispersed on the zirconium phosphate matrix through tetrabutyl titanate hydrolysis and calcination. The nano-scale TiO2 was obtained by applying the appropriate ratio of tetrabutyl titanate and layered zirconium phosphate in reaction. XRD, N2-sorption, FT-IR, UV-vis, SEM and TEM were used to characterize the structure and phtocatalytic properties of the samples. The photocatalytic performance of synthesized nano-scale TiO2 doped zirconium phosphates was studied by degradation of Rhodamine B (RhB). It is found that the scavenging rate of RhB could be up to 65% within 90 min under the visible light irradiation due to the relatively large active surface area and compact size of TiO2. This study highlights the potential application of TiO2 doped layered zirconium phosphate as a novel photocatalyst in photocatalytic degradation of organic pollutants.

The Accumulation of Psoralen Contributes to Its Hepatotoxicity Revealed by Pharmacokinetic and Toxicokinetic Study after Repeated Administration.

Psoralen is a furanocoumarin compound found in many herb medicines and is claimed to contribute to the hepatotoxicity caused by lots of traditional Chinese medicine. So far, there has been no research on the differences in pharmacokinetics of single and repeated dosing of psoralen. Moreover, the research on the cumulative toxicity of low concentration and long-term administration on cells has not been reported. Therefore, this study investigated the pharmacokinetic differences and the accumulated cytotoxicity of psoralen from repeated administration. The study found that after single or repeated administration of psoralen for 3 months at various dosages (14, 28, and 56 mg/kg), the pharmacokinetic parameters of female rats between single dose and repeated dose administration are totally different. Compared with a single administration, multiple administrations increased psoralen's in vivo exposure, prolonged the peak time, prolonged the half-life of the drug, reduced the drug clearance rate, and prolonged the drug's stay in the body. HepG2 cells were exposed to low doses (5, 10, 20, or 40 µM) of psoralen for 1, 2, 3, or 4 days. A 20 and 40 µM dose of psoralen did not induced cell death in the 1st day but significantly decreased the cell viability at the 3rd and 4th day of repeated administration, respectively. In addition, multiple administrations of psoralen decreased cell viability due to G2 arrest.