Simultaneous determination of phenolic compounds in Equisetum palustre L. by ultra high performance liquid chromatography with tandem mass spectrometry combined with matrix solid-phase dispersion extraction
Wei Z.,Northeast Forestry University |
Pan Y.,Jiangsu Kanion Parmaceutical Co. |
Li L.,Northeast Forestry University |
Huang Y.,Northeast Forestry University |
And 4 more authors.
Journal of Separation Science | Year: 2014
A method based on matrix solid-phase dispersion extraction followed by ultra high performance liquid chromatography with tandem mass spectrometry is presented for the extraction and determination of phenolic compounds in Equisetum palustre. This method combines the high efficiency of matrix solid-phase dispersion extraction and the rapidity, sensitivity, and accuracy of ultra high performance liquid chromatography with tandem mass spectrometry. The influential parameters of the matrix solid-phase dispersion extraction were investigated and optimized. The optimized conditions were as follows: silica gel was selected as dispersing sorbent, the ratio of silica gel to sample was selected to be 2:1 (400/200 mg), and 8 mL of 80% methanol was used as elution solvent. Furthermore, a fast and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the determination of nine phenolic compounds in E. palustre. This method was carried out within <6 min, and exhibited satisfactory linearity, precision, and recovery. Compared with ultrasound-assisted extraction, the proposed matrix solid-phase dispersion procedure possessed higher extraction efficiency, and was more convenient and time saving with reduced requirements on sample and solvent amounts. All these results suggest that the developed method represents an excellent alternative for the extraction and determination of active components in plant matrices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Li M.,Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation |
Shi A.,Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation |
Pang H.,Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation |
Xue W.,Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation |
And 9 more authors.
Journal of Ethnopharmacology | Year: 2014
Ethnopharmacological relevance: The root of Scutellaria baicalensis Georgi has been used extensively in traditional Chinese medicine for the treatment of inflammation, fever, cough, dysentery, and hypertension. Baicalein is a flavonoid isolated from the root of Scutellaria baicalensis Georgi and is a novel neuroprotective agent under development for the treatment of Parkinson's disease. We aimed to investigate the pharmacokinetic (PK) properties of baicalein and its main metabolite, bacalin, after single-dose administration in healthy Chinese subjects. The safety and tolerability of baicalein were also assessed. Materials and methods: This was a Phase I, randomized, double-blind, single-dose trial of baicalein (100-2800 mg) in 72 healthy adults. Samples of blood, urine and feces were collected at regular intervals up to 48 h after administration of the study drug. Baicalein and baicalin were then analyzed using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The maximum concentration that the drug achieved after dosing (Cmax), time to Cmax (Tmax), terminal half-life (t1/2), area under the curve from time zero to time of last quantifiable concentration (AUC(0, t)), area under the curve from time zero to infinity (AUC(0, ∞)), apparent total plasma clearance (CL/F), and apparent total volume of distribution (V/F) were determined using non-compartmental models. Dose proportion was tested using a method combining the equivalence criterion and power model. Physical examinations, vital signs, ECG findings, hematology, and urinalysis were monitored before and at regular intervals after administration of the study drug. Results: The PK profile of baicelein and baicelin was characterized by a median Tmax of 0.75-3.5 h and 0.5-3 h, respectively, followed by a multiphasic profile with a t1/2 of 1.90-15.01 h and 4.22-10.80 h, respectively. The estimates of the proportionality coefficient (90% CI) for Cmax, AUC0-t and AUC0-∞ were 0.83 (0.70-0.96), 0.91 (0.81-1.00) and 0.92 (0.82-1.02), respectively. All values overlapped within the pre-specified range of (0.89-1.11), (0.93-1.07), and (0.93-1.07), respectively. Dose proportionality was inconclusive for a baicalein dose range of 100-2800 mg. The total urinary clearance of baicalein and baicalin was <1%. Approximately 27% of baicalein was eliminated as unchanged drug in feces. Baicalein was well tolerated. Eleven treatment-related adverse events were observed, and all were rated as "mild" and resolved without further treatment. No serious adverse events occurred. Conclusions: Single oral doses of 100-2800 mg of baicalein were safe and well tolerated by healthy subjects. Clinical laboratory assessments showed no signs of toxicity in the liver or kidney. The favorable safety profile and PK properties warrant further clinical studies for baicalein. © 2014 Elsevier Ireland Ltd. All rights reserved.
Du P.-P.,Beijing University of Chinese Medicine |
Zhao B.-C.,Beijing University of Chinese Medicine |
Wang W.-P.,Beijing University of Chinese Medicine |
An J.,Beijing University of Chinese Medicine |
And 5 more authors.
Zhongguo Zhongyao Zazhi | Year: 2013
Using sustained release tablets of Ginkgo bibolia extract as model drug, discuss technical feasibility of using biotic index to evaluate sustained release tablets. Chosing two pharmacological indicatrix: antioxidant ability and inhibition of platelet aggregation, to investigate the influence factors on experimental result, optimize the method and experiment condition, and set up pharmacological indicatrix evaluation method.Using those methods to determinate biological effects of dissolved liquid. Drawing release curves and biological effects curves, discussing their correlation. A good correlation was observed, illustrating that pharmacological indicatrix could evaluate sustained release tablets.
Yang Y.,Dalian University of Technology |
Wang J.,Dalian University of Technology |
Li Y.,Dalian University of Technology |
Xiao W.,Jiangsu Kanion Parmaceutical Co. |
And 5 more authors.
Soft Matter | Year: 2013
Tuberculosis caused by Mycobacterium tuberculosis (Mtb), is a major factor of death around the world. Mtb protein tyrosine phosphatase B (MptpB), a virulent phosphatase encoded by Mtb, is a potential target for the treatment of tuberculosis. To explore the structure features of 134 indolin-2-on-3- spirothiazolidinones as MptpB inhibitors, in this work, a set of ligand- and receptor-based 3D-QSAR studies were, for the first time, carried out using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques. Splitting of the training and test sets was constructed by Kohonen's self-organizing map algorithm. Additionally, to profile the possible binding modes of these inhibitors, molecule docking and molecular dynamics (MD) simulations were performed as well. The optimal QSAR models built on both ligand- and receptor-based alignments exhibit proper reliabilities and predictive abilities as illustrated by their statistical results that for ligand-based alignment CoMFA and CoMSIA models obtain Q2 = 0.662, Rncv 2 = 0.799, R pre 2 = 0.757, and Q2 = 0.736, R ncv 2 = 0.847, Rpre 2 = 0.866; whereas for docking-based one achieve Q2 = 0.536, Rncv 2 = 0.894, Rpre 2 = 0.823, and Q2 = 0.498, Rncv 2 = 0.812, Rpre 2 = 0.833, respectively. Furthermore, the contours generated from these models are well consistent with the docking and MD results we performed. Our findings are: (1) Indolin-2-on-3-spirothiazolidinones may bind to the MptpB with a "cockhorse" conformation, which is stabilized by eight H-bonds formed with the surrounding residues (Arg166, Cys160, Ala162, Lys164, His94 and Glu129), one cation-π interaction with the side chain of Arg166 and two hydrophobic interactions in the binding site. (2) Introduction of bulky and electropositive substituents at R3, hydrophobic substituents around rings A and E can improve the inhibition potency. (3) Nitro group at R 2 position of 2-oxindole core plays a crucial role for the biological activities, and may also be essential to the water-mediated H-bond networks. (4) For 8, 10-positions of the thiazolidinone ring and 13-position of isoxazole, the groups acting as H-bond acceptor are favorable for increasing the activity. All these results are expected to be useful in the discovery of novel and more potent MptpB inhibitors. © The Royal Society of Chemistry 2013.
Zhou J.,Nanjing University |
Ma H.,Nanjing University |
Fan X.,Nanjing University |
Xiao W.,Jiangsu Kanion Parmaceutical Co. |
And 3 more authors.
Journal of Chinese Integrative Medicine | Year: 2012
Objective: To investigate the mechanism of binding of human serum albumin (HSA) with potential sensitinogen, including chlorogenic acid and two isochlorogenic acids (3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid). Methods: By using the docking algorithm of computer-aided molecular design and the Molegro Virtual Docker, the crystal structures of HSA with warfarin and diazepam (Protein Data Bank ID: 2BXD and 2BXF) were selected as molecular docking receptors of HSA sites I and II. According to docking scores, key residues and H-bond, the molecular docking mode was selected and confirmed. The molecular docking of chlorogenic acid and two isochlorogenic acids on sites I and II was compared based on the above design. Results: The results from molecular docking indicated that chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid could bind to HSA site I by high affinity scores of -112.3, -155.3 and -153.1, respectively. They could bind to site II on HSA by high affinity scores of -101.7, -138.5 and -133.4, respectively. In site I, two isochlorogenic acids interacted with the key apolar side-chains of Leu238 and Ala291 by higher affinity scores than chlorogenic acid. Furthermore, the H-bonds of isochlorogenic acids with polar residues inside the pocket and at the entrance of the pocket were different from chlorogenic acid. Moreover, the second coffee acyl of isochlorogenic acid occupied the right-hand apolar compartment in the pocket of HSA site I. In site II, the second coffee acyl of isochlorogenic acid formed the H-bonds with polar side-chains, which contributed isochlorogenic acid to binding with site II of HSA. Conclusion: The isochlorogenic acids with two coffee acyls have higher binding abilities with HSA than chlorogenic acid with one coffee acyl, suggesting that isochlorogenic acids binding with HSA may be sensitinogen.