Journal of Pharmaceutical Analysis

2019, 9(5): 封3-封4.

Abstract(105) PDF(0)

Abstract:

Carbon nanotubes:Evaluation of toxicity at biointerfaces

Debashish Mohanta, Soma Patnaik, Sanchit Sood, Nilanjan Das

2019, 9(5): 293-300.

Abstract(432) PDF(14)

Abstract:
Carbon nanotubes (CNTs) are a class of carbon allotropes with interesting properties that make them productive materials for usage in various disciplines of nanotechnology such as in electronics equip-ments, optics and therapeutics. They exhibit distinguished properties viz., strength, and high electrical and heat conductivity. Their uniqueness can be attributed due to the bonding pattern present between the atoms which are very strong and also exhibit high extreme aspect ratios. CNTs are classified as single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) on the basis of number of sidewalls present and the way they are arranged spatially. Application of CNTs to improve the performance of many products, especially in healthcare, has led to an occupational and public exposure to these nanomaterials. Hence, it becomes a major concern to analyze the issues pertaining to the toxicity of CNTs and find the best suitable ways to counter those challenges. This review summarizes the toxicity issues of CNTs in vitro and in vivo in different organ systems (bio interphases) of the body that result in cellular toxicity.

Essential oils of Origanum compactum increase membrane permeability, disturb cell membrane integrity, and suppress quorum-sensing phenotype in bacteria

Abdelhakim Bouyahya, Jamal Abrini, Nadia Dakka, Youssef Bakri

2019, 9(5): 301-311.

Abstract(235) PDF(5)

Abstract:
The aim of this study was to investigate antibacterial activity of Origanum compactum essential oils collected at three phenological stages on Escherichia coli and Bacillus subtilis. The antibacterial activity was evaluated using the agar-well diffusion assay. The MIC and MBC values were determined using the micro-dilution assay. The investigation of the antibacterial action was carried out by the evaluation of the effect of O. compactum essential oils on the antibacterial kinetic growth, the integrity of cell membrane and permeability of the cell membrane. The anti-quorum sensing activity was tested by the inhibition of the biofilm formation. The findings of this study showed that O. compactum essential oil has potent antibacterial activities against E. coli and B. subtilis. The lowest inhibition value against B. subtilis was obtained with O. compactum essential oil at the post-flowering stage (MIC = MBC = 0.0312% (v/v)). The antibacterial mechanisms of O. compactum essential oils are related to the disturbing of the cell mem-brane integrity and the increasing of the membrane permeability, which leads to the leakage of genetic materials (DNA and RNA). Moreover, O. compactum essential oils inhibited the formation of the biofilms, a phenotype that has been known to be quorum sensing regulated.

Elucidating the interaction of kansui and licorice by comparative plasma/tissue metabolomics and a heatmap with relative fold change

Yan-Yan Chen, Juan Shen, Yu-Ping Tang, Jin-Gao Yu, Jing Wang, Shi-Jun Yue, Jie Yang, Jia-Qian Chen, Li-Mei Feng, Zhen-Hua Zhu, Wei-Wei Tao, Li Zhang, Jin-Ao Duan

2019, 9(5): 312-323.

Abstract(137) PDF(3)

Abstract:
Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate com-bination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM"Eighteen Incompatible Medicaments", are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphin-ganine were screened out as the principal alternative biomarkers of compatibility group; sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of in-compatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM"Eighteen Incompatible Medicaments".

Temperature and eluent composition effects on enantiomer separation of carvedilol by high-performance liquid chromatography on immobilized amylose-based chiral stationary phases

Cristina Panella, Rosella Ferretti, Adriano Casulli, Roberto Cirilli

2019, 9(5): 324-331.

Abstract(139) PDF(5)

Abstract:
Carvedilol is a chiral drug with potent antihypertensive and antianginal activities. Although it is clinically used as a racemic mixture, its enantiomers show different pharmacokinetic and pharmacodynamic profiles. Here, the direct chiral separation of racemic drug by high performance liquid chromatography using two immobilized-type amylose-based chiral stationary phases is presented. Some chromato-graphic parameters, such as retention and selectivity, were determined under multimodal eluent con-ditions and different temperatures. A temperature-dependent inversion of the elution order of enantiomers was observed in the operative temperature range of chiral chromatographic support. Finally, an effective direct enantioselective method was successfully applied to the separation of the enantiomers of carvedilol on a semipreparative scale.

Composition analysis and antioxidant activities of the Rhus typhina L. stem

Ting Liu, Zhaoqin Li, Ruiyun Li, Yue Cui, Yunli Zhao, Zhiguo Yu

2019, 9(5): 332-338.

Abstract(79) PDF(5)

Abstract:
The present investigation reports the chemical composition of the Rhus typhina L. stem identified via mass spectrometry and NMR as gallic acid, 1-O-galloyl-β-D-glucose, tryptophan, scopolin, methyl gallate, fustin, quercetin, rutin, and 1,2,3,4,6-penta-O-galloyl-β-D-glucose. The antioxidant properties and the chemical composition contents of the R. typhina L. stem grown in different regions in China were de-termined. To determine the antioxidant activity, a total phenolic content analysis, 2, 2-diphenyl-1-pi-crylhydrazyl radical scavenging activity assay, ferric reducing antioxidant power assay, andβ-carotene linoleic acid model system were conducted. The results showed that the Rhus typhina L. stem possessed high antioxidant capacities due to its high phenolic content. The contents of the nine isolated compounds were determined by UPLC-ESI-MS/MS. The calibration curves of the nine isolated compounds were linear within the concentration range and the average recoveries were high. The result showed that 1-O-galloyl-β-D-glucose, gallic acid, methyl gallate, and 1,2,3,4,6-penta-O-galloyl-β-D-glucose could be the compounds mainly responsible for the antioxidant capacity of the R. typhina L. stem. This reveals that the R. typhina L. stem is a good source of antioxidants.

Irbesartan desmotropes:Solid-state characterization, thermodynamic study and dissolution properties

Andrea Mariela Araya-Sibaja, Carlos Eduardo Maduro de Campos, Cinira Fandaruff, José Roberto Vega-Baudrit, Teodolito Guillén-Girón, Mirtha Navarro-Hoyos, Silvia Lucía Cuffini

2019, 9(5): 339-346.

Abstract(116) PDF(2)

Abstract:
Irbesartan (IBS) is a tetrazole derivative and antihypertensive drug that has two interconvertible struc-tures, 1H-and 2H-tautomers. The difference between them lies in the protonation of the tetrazole ring. In the solid-state, both tautomers can be isolated as crystal forms A (1H-tautomer) and B (2H-tautomer). Studies have reported that IBS is a polymorphic system and its forms A and B are related monotropically. These reports indicate form B as the most stable and less soluble form. Therefore, the goal of this contribution is to demonstrate through a complete solid-state characterization, thermodynamic study and dissolution properties that the IBS forms are desmotropes that are not related monotropically. However, the intention is also to call attention to the importance of conducting strict chemical and in solid-state quality controls on the IBS raw materials. Hence, powder X-ray diffraction (PXRD) and Raman spectroscopy (RS) at ambient and non-ambient conditions, differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared (FT-IR) and scanning electron microscopy (SEM) techniques were applied. Furthermore, intrinsic dissolution rate (IDR) and structural stability studies at 98%relative humidity (RH), 25 ?C and 40 ?C were conducted as well. The results show that in fact, form A is approximately four-fold more soluble than form B. In addition, both IBS forms are stable at ambient conditions. Nevertheless, structural and/or chemical instability was observed in form B at 40 ?C and 98%RH. IBS has been confirmed as a desmotropic system rather than a polymorphic one. Consequently, forms A and B are not related monotropically.

Voltammetric sensor based on cobalt-poly(methionine)-modified glassy carbon electrode for determination of estriol hormone in pharmaceuticals and urine

Eliziana S. Gomes, Fernando R.F. Leite, Bruno R.L. Ferraz, Henrique A.J.L. Mour?o, Andréa R. Malagutti

2019, 9(5): 347-357.

Abstract(130) PDF(3)

Abstract:
A voltammetric sensor based on the electropolymerization of cobalt-poly(methionine) (Co-poly(Met)) on a glassy carbon electrode (GCE) was developed and applied for the determination of estriol by differential pulse voltammetry (DPV) for the first time. The electrochemical properties of the Co-poly(Met)/GCE were analysed by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used to characterize the polymers on the GCE surface. The deposition of the Co-poly(Met) film on the GCE surface enhanced the sensor electronic transfer. CV studies revealed that estriol exhibits an irreversible oxidation peak at t0.58 V for the Co-poly(Met)/GCE (vs. Ag/AgCl reference electrode) in 0.10 mol/L Britton-Robinson buffer solution (pH = 7.0). Different voltammetric scan rates (10-200 mV/s) suggested that the estriol oxidation on the Co-poly(Met)/GCE surface is controlled by adsorption and diffusion processes. Based on the optimized DPV conditions, the linear responses for estriol quantification were from 0.596μmol/L to 4.76μmol/L (R2 = 0.996) and from 5.66μmol/L to 9.90μmol/L (R2 = 0.994) with a limit of detection (LOD) of 0.0340μmol/L and a limit of quantification (LOQ) of 0.113μmol/L. The DPV-Co-poly(Met)/GCE method provided good intra-day and inter-day repeatability with RSD values lower than 5%. Also, no interference of real sample matrices was observed on the estriol voltammetric response, making the DPV-Co-poly(Met)/GCE highly selective for estriol. The accuracy test showed that the estriol recovery was in the ranges 96.7%-103%and 98.7%-102%for pharmaceutical tablets and human urine, respectively. The estriol quantification in pharmaceutical tablets performed by the Co-poly(Met)/GCE-assisted DPV method was comparable to the official analytical protocols.

Highly sensitive simultaneous electrochemical determination of myricetin and rutin via solid phase extraction on a ternary Pt@r-GO@MWCNTs nanocomposite

Satar Tursynbolat, Yrysgul Bakytkarim, Jianzhi Huang, Lishi Wang

2019, 9(5): 358-366.

Abstract(100) PDF(2)

Abstract:
The simultaneous electrochemical determination of myricetin and rutin remains a challenge due to their indistinguishable potentials. To solve this problem, we constructed a ternary platinum nanoparticle, reduced graphene oxide, multi-walled carbon nanotubes (Pt@r-GO@MWCNTs) nanocomposite via a facile one-pot synthetic method. Under the optimized conditions, the ternary Pt@r-GO@MWCNTs nanocomposite exhibited good electrocatalytic activity toward myricetin and rutin via solid phase extraction and excellent performance for the simultaneous determination of myricetin and rutin. The oxidation peak current of myricetin was proportional to its concentrations in the range of 0.05-50μM with a detection limit of 0.01μM (S/N = 3). The linear range for rutin was 0.05-50μM with a detection limit of 0.005μM (S/N = 3). The ternary nanocomposite sensor also exhibited good reproducibility and stability, and was successfully used for the simultaneous determination of myricetin and rutin in real orange juice samples with recoveries ranging between 100.57%and 108.46%.

Pharmacokinetics and enterohepatic circulation of jervine, an antitumor steroidal alkaloid from Veratrum nigrum in rats

Bingjing Zheng, Caihong Wang, Wenwen Song, Xiaoxia Ye, Zheng Xiang

2019, 9(5): 367-372.

Abstract(92) PDF(2)

Abstract:
Jervine, a novel steroidal alkaloid from Veratrum nigrum L., exhibits both antitumor effect and potential toxicity. The aim of study was to characterize the pharmacokinetic behaviors and enterohepatic circu-lation of jervine in rats. A rapid and simple ultra-high performance liquid chromatography-tandem mass spectrometric method was developed and validated for quantification of jervine and alpinetin (internal standard) in rat plasma. After extraction from rat plasma by a simple protein-precipitation method, the analyte was separated on a C18 column (2.1 mm × 50 mm, 1.7μm) using water with 0.1%formic acid and acetonitrile as the mobile phase delivered at a flow rate of 0.4 mL/min. Jervine and alpinetin were determined in the positive mode with multiple reaction monitoring (MRM) of the ion transitions at m/z 426.3→108.8 and m/z 271.0→166.9, respectively. Molecular docking method was used to investigate the binding of jervine to p-glycoprotein and dehydroepiandrosterone sulfotransferase. The method was well validated within acceptance limits including specificity, matrix effect, recovery, precision, accuracy, and stability, and was successfully applied to the pharmacokinetic study of jervine after oral and intravenous administration to rats. Jervine presented a small volume of distribution, fast absorption, high oral bioavailability, and enterohepatic circulation. The enterohepatic circulation was first observed in veratrum alkaloids, and was further investigated by molecular docking studies, which was related to the binding of jervine to p-glycoprotein and dehydroepiandrosterone sulfotransferase. The pharmacokinetic properties and enterohepatic circulation of jervine in rats provided a significant basis for the drug-drug interaction and toxicity study in the future.

2019 Vol. 9, No. 5