Pharmacokinetic characteristics of psoralen,isopsoralen,psoralenoside and isopsoralenoside in rats after oral administration of Psoraleae Fructus extract / 中国中药杂志

Coumarins are the main active components in Psoraleae Fructus. To study the multi-component pharmacokinetics of Psoraleae Fructus, this study established a sensitive and rapid ultra-pressure liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of psoralen, isopsoralen, psoralenoside, and isopsoralenoside in rat plasma. After validation, the method was applied to the investigation of pharmacokinetics of psoralen, isopsoralen, psoralenoside, and isopso-ralenoside in rats after single and multiple administration of Psoraleae Fructus extract. The results revealed that the exposure of psoralen and isopsoralen in rat plasma was high after a single intragastric administration of Psoraleae Fructus extract, with an AUC_(0-∞) of 443 619-582 680 and 167 314-276 903 ng·mL~(-1)·h~(-1), respectively. Compared with these two compounds, the exposure of psoralenoside and isopsoralenoside was lower with marked gender difference. After 7-day administration of Psoraleae Fructus extract to rats, the AUC_(0-∞) of psoralen and isopsoralen was 29 701-81 783 and 39 234-89 914 ng·mL~(-1)·h~(-1), respectively, which was significantly lower than that at the first day(P<0.05), and that of psoralenoside and isopsoralenoside was 7 360-19 342 and 8 823-45 501 ng·mL~(-1)·h~(-1), respectively. There was no significant gender difference in exposure of psoralenoside and isopsoralenoside in male and female rats. However, the exposure of psoralenoside and isopsoralenoside in male rats was reduced(P<0.05), and the t_(1/2) and mean residence time(MRT) were shortened, suggesting that the removal of these two compounds from the body was accelerated.

Rapid and simultaneous determination of 10 active components of Psoraleae Fructus in beagle dog plasma using UPLC-MS/MS and its application in pharmacokinetic study / 中国中药杂志

An UPLC-MS/MS method for rapid and simultaneous determination of psoralen, isopsoralen, apigenin, genistein, bavaisoflavone, neobavaisoflavone, bavachin, bavachinin, psoralenoside, and isopsoralenoside of Psoraleae Fructus in beagle dog plasma was established, and then the method was applied in the pharmacokinetic study after oral administration of Psoraleae Fructus extract to beagle dogs. The pharmacokinetic parameters were calculated by the software of WinNonlin. A Waters HSS-T3 column(2.1 mm×100 mm,1.8 μm)was used for liquid chromatography separation with acetonitrile-water(containing 0.004% formic acid) as the mobile phase for gradient elution.The mass spectrometry was detected using electrospray ion source(ESI) under multi-reaction monitoring mode(MRM), as well as positive ion mode. Analysis time only takes 8.5 min. The methodological study in terms of specificity, accuracy, precision, linear range, recovery, matrix effect, and stability, was validated. The LC-MS analysis method established in this experiment was simple, specific, accurate, reliable, and meet the requirement of pharmacokinetic study in plasma after administration of Psoraleae Fructus extract to beagle dogs. Six beagle dogs received intragastric administration of Psoraleae Fructus extract, T_(max) of 10 chemical components is 1.92-5.67 h; among them, C_(max) of psoralen, isopsoralen, psoralenoside and isopsoralenoside is 383-3 613 ng·mL~(-1), and AUC_(0-∞) is 3 556-18 949 ng·h·mL~(-1), t_(1/2) is 2.45-4.83 h. C_(max) of the remaining six compounds is 0.81-19.9 ng·mL~(-1), AUC_(0-∞ )is 6.54-178 ng·h·mL~(-1), t_(1/2) is 2.95-7.29 h. The UPLC-MS/MS analysis method established in this study was proved to be accurate and sensitive that it can be applied to the pharmacokinetic study of beagle dogs after oral administration of Psoraleae Fructus extract.

Chemical Constituents of Psoraleae Fructus and Its Main Toxic Ingredients / 中国实验方剂学杂志

Psoraleae Fructus (Buguzhi) is dried mature fruit of Psoralea corylifolia. It is spicy and bitter in favor and warm in nature, and distributed to kidney and spleen meridians. Psoralea Fructus has the effects of warming kidney and tonifying Yang,absorbing Qi and relieving asthma,warming spleen and stopping diarrhea; for external use,it can remove beverage. It is mainly used to treat impotence and nocturnal emission cold and knee pain,kidney deficiency and asthma caused by kidney Yang deficiency; for external use, it can treat vitiligo and alopecia areata. Its principle chemical components are coumarins,monoterpene phenols,flavonoids,with an estrogen-like effect as well as anti-inflammatory,antibacterial,antifungal,anti-oxidation,anti-tumor and immunomodulatory activities, and can be used for the prevention and treatment of osteoporosis,bacterial infections,asthma and osteoarthritis. However,the long-term administration with large doses of psoralen have the potential risk of causing liver damage,with phototoxicity,nephrotoxicity and reproductive toxicity,which restricts its application in clinical therapy. Therefore,it is essential to fully understand the chemical composition and mechanism of psoralen. Through the review and summarization of literatures about psoralen at home and abroad,this article systematically reviews the chemical constituents and toxicity of Psoralea Fructus, provides Chinese and English names,structural formulas,molecular formulas,molecular weights,CAS numbers of the compounds and the toxicity information about psoralen reported in recent years, in order to provide a reference for further study on the compositional spectrum and pharmacokinetics,toxic kinetic studies and clinical medication safety of psoralen.

Qualitative characterization of flavonoids in Scutellariae Radix by using PREC-IDA-EPI / 中国中药杂志

Flavonoids are the most abundant constituents and induce these the rapeutic effects against inflammation, gastrointestinal infections, cardiovascular diseases, and respiratory. Most of these flavonoids have low content in Scutellarie Radix. It was difficult to detect some minor compounds by using LC-MS method with full scan. Based on the review of flavonoids that had been extracted from Scutellariae Radix, a method with PREC-IDA-EPI technique was developed and applied to Scutellariae Radix by using UPLC-MS/MS. A total of 97 flavonoids were identified, including 29 aglycones and 68 -glycosides. This study laid the foundation for pharmacodynamicss of Scutellariae Radix.It is believed that an individual detection scheme based on the PREC-IDA-EPI technique could be used to identify unknown compounds.

Pharmacokinetics of the prototype and hydrolyzed carboxylic forms of ginkgolides A, B, and K administered as a ginkgo diterpene lactones meglumine injection in beagle dogs / 中国天然药物

Ginkgo diterpene lactones meglumine injection (GDLI) is a commercially available product used for neuroprotection. However, the pharmacokinetic properties of the prototypes and hydrolyzed carboxylic forms of the primary components in GDLI, i.e., ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), have never been fully evaluated in beagle dogs. In this work, a simple, sensitive, and reliable method based on ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was developed, and the prototypes and total amounts of GA, GB, and GK were determined in beagle dog plasma. The plasma concentrations of the hydrolyzed carboxylic forms were calculated by subtracting the prototype concentrations from the total lactone concentrations. For the first time, the pharmacokinetics of GA, GB, and GK were fully assessed in three forms, i.e., the prototypes, the hydrolyzed carboxylic forms, and the total amounts, after intravenous administration of GDLI in beagle dogs. It was shown that ginkgolides primarily existed in the hydrolyzed form in plasma, and the ratio of hydrolysates to prototype forms of GA and GB decreased gradually to a homeostatic ratio. All of the three forms of the three ginkgolides showed linear exposure of AUC to the dosages. GA, GB, and GK showed a constant half-life approximately 2.7, 3.4, and 1.2 h, respectively, which were consistent for the forms at three dose levels (0.3, 1.0, and 3.0 mg·kg) and after a consecutive injection of GDLI for 7 days (1.0 mg·kg).

Impact of parameter fluctuations on the performance of ethanol precipitation in production of Re Du Ning Injections, based on HPLC fingerprints and principal component analysis / 中国天然药物

The present study was designed to determine the relationships between the performance of ethanol precipitation and seven process parameters in the ethanol precipitation process of Re Du Ning Injections, including concentrate density, concentrate temperature, ethanol content, flow rate and stir rate in the addition of ethanol, precipitation time, and precipitation temperature. Under the experimental and simulated production conditions, a series of precipitated resultants were prepared by changing these variables one by one, and then examined by HPLC fingerprint analyses. Different from the traditional evaluation model based on single or a few constituents, the fingerprint data of every parameter fluctuation test was processed with Principal Component Analysis (PCA) to comprehensively assess the performance of ethanol precipitation. Our results showed that concentrate density, ethanol content, and precipitation time were the most important parameters that influence the recovery of active compounds in precipitation resultants. The present study would provide some reference for pharmaceutical scientists engaged in research on pharmaceutical process optimization and help pharmaceutical enterprises adapt a scientific and reasonable cost-effective approach to ensure the batch-to-batch quality consistency of the final products.