[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.

Determination of multicomponents from Zhuanggu Guanjie capsule in rat plasma by UHPLC-MS/MS and pharmacokinetic study.

Aim: To develop a UHPLC-MS/MS method for the quantification of 12 constituents in rat plasma after oral administration of Zhuanggu Guanjie. Methods: Constituent separation was performed on a C18 column, and the mass spectrometric detection was performed in multiple reaction monitoring mode with a positive-negative ionization mode. Results: The method was successfully applied to the pharmacokinetic study of these 12 constituents after rats taking Zhuanggu Guanjie capsules. The results showed that psoralen, isopsoralen and aspersaponin VI were the key effective components and had high exposure. Conclusion: A rapid, simple and sensitive ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry method for the detection of 12 components in rat plasma after taking Zhuanggu Guanjie was developed and applied in this pharmacokinetics study.

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.

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.