JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2017
·
IF 3.255
Bingchen Ouyang,Fang Zhou,Le Zhen,Ying Peng,Jianguo Sun,Qianying Chen,Xiaoliang Jin,Guangji Wang,Jingwei Zhang
Tenofovir (TFV), a first-line anti-viral agent, has been prepared as various forms of prodrugs for better bioavailability, lower systemic exposure and higher target cells loading of TFV to enhance efficacy and reduce toxicity. TFV undergoes intracellular phosphorylation to form TFV diphosphate (TFV-DP) in target cell to inhibit viral DNA replication. Hence, TFV-DP is the key active metabolite that exhibits anti-virus activity, its intracellular exposure and half-life determine the final activity. Therefore, simultaneous monitoring prodrug, TFV and TFV-DP in target cells will comprehensively evaluate TFV prodrugs, both considering the stability of ester prodrug, and the intracellular exposure of TFV-DP. Thus we intended to develop a convenient general analytical method, taking tenofovir alafenamide (TAF) as a representative of TFV prodrugs. A sensitive LC–MS/MS method was developed, and TAF, TFV and TFV-DP were separated on a XSelect HSS T3 column (4.6 mm × 150 mm, 3.5 μm, Waters) with gradient elution after protein precipitation. The method provided good linearity for all the compounds (2–500 nM for TFV and TAF; 20–5000 nM for TFV-DP) with the correlation coefficients ( r ) greater than 0.999. Intra- and inter-day accuracies (in terms of relative error, RE < 10.4%) and precisions (in terms of coefficient of variation, CV < 14.1%) satisfied the standard of validation. The matrix effect, recovery and stability were also within acceptable criteria. Finally, we investigated the intracellular pharmacokinetics of TAF and its active metabolites in HepG2.2.15 cells with this method.
研究领域:
药理学
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分析化学
·
病毒学
✓ 已验证
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2019
·
IF 2.813
Lizhi Zhao,Zhou Li,Zhen Zhou,Xiuyuan Kang,Baihuan Fang,Huan Ma,Qinghua Ge
An ultra performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) method has been developed for the simultaneous determination of tenofovir alafenamide (TAF) and it's metabolite tenofovir (TFV) in human plasma. The analytes and inter standards, TAF-d5 and TFV-d6 were extracted from human plasma via protein precipitation (PPT) and only 200 μl plasma was needed. Chromatography separation was achieved on a Waters Acquity UHPLC HSS T3 column (100 * 2.1 mm, 1.8 μm) with a total run time of 10 min. A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) mode under positive ionization mode with an electrospray ionization (ESI) interface. The method was developed and validated over the concentration range of 4.00–400 ng/ml for TAF and 0.400–40.0 ng/ml for TFV, respectively. Each analyte in acidified plasma was found stable during sample storage, preparation and analytical procedures. The method has successfully overcame the lack of stability of analytes in plasma samples and been applied to the pharmacokinetics study of treatment of 25 mg TAF in 8 healthy volunteers under fasting condition.
研究领域:
药物分析
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临床药理学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2022
·
IF 5.304
Weili Zeng,Jingyun Xiao,Liangyuan Yao,Yanping Wei,Jinsong Zuo,Wenming Li,Jianhua Ding,Quanguo He
Tenofovir (TFV) is an antiviral drug base for the treatment of diseases caused by retroviruses. Quantitative detection is the key to the effective application of TFV. In this work, a composite modified electrode (La 2 O 3 -ZrO 2 -MWCNTs/GCE) was prepared and used for the electrochemical detection of TFV. The materials were characterized by XRD, SEM, EDS. The performance of the sensor was investigated by cyclicvoltammetry, electrochemical impedance specttoscopy and differential pulse voltammetry. La 2 O 3 -ZrO 2 -MWCNTs/GCE greatly improved the electrochemical response of TFV. Under optimal conditions, the proposed electrochemical method, ranging from 0.7−100.0 μM had a good linear range with a detection limit of 0.219 μM. The sensitivity, reproducibility and selectivity of the sensor achieved satisfactory results, and has been applied to the determination of TFV in biological samples, with satisfactory results.
研究领域:
分析化学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Biosensors-Basel
·
2022
·Vol. 12
·期 12
·1123
·
IF 5.743
Jingyun Xiao,Shuting Shi,Liangyuan Yao,Jinxia Feng,Jinsong Zuo,Quanguo He
Tenofovir disoproxil fumarate (TDF) is an antiretroviral medication with significant curative effects, so its quantitative detection is important for human health. At present, there are few studies on the detection of TDF by electrochemical sensors. This work can be a supplement to the electrochemical detection of TDF. Moreover, bare electrodes are susceptible to pollution, and have high overvoltage and low sensitivity, so it is crucial to find a suitable electrode material. In this work, zirconium oxide (ZrO2) that has a certain selectivity to phosphoric acid groups was synthesized by a hydrothermal method with zirconyl chloride octahydrate as the precursor. A composite modified glassy carbon electrode for zirconium oxide-chitosan-multiwalled carbon nanotubes (ZrO2-CS-MWCNTs/GCE) was used for the first time to detect the TDF, and achieved rapid, sensitive detection of TDF with a detection limit of sub-micron content. The ZrO2-CS-MWCNTs composite was created using sonication of a mixture of ZrO2and CS-MWCNTs solution. The composite was characterized using scanning electron microscopy (SEM) and cyclic voltammetry (CV). Electrochemical analysis was performed using differential pulse voltammetry (DPV). Compared with single-material electrodes, the ZrO2-CS-MWCNTs/GCE significantly improves the electrochemical sensing of TDF due to the synergistic effect of the composite. Under optimal conditions, the proposed method has achieved good results in linear range (0.3~30 μM; 30~100 μM) and detection limit (0.0625 μM). Moreover, the sensor has the merits of simple preparation, good reproducibility and good repeatability. The ZrO2-CS-MWCNTs/GCE has been applied to the determination of TDF in serum and urine, and it may be helpful for potential applications of other substances with similar structures.Keywords:Tenofovir disoproxil fumarate;zirconium oxide;multiwalled carbon nanotubes;differential pulse voltammetry;biological samples
研究领域:
药物分析
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电化学传感器
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Chenyang Zhao,Xiaolei Wang,Yanbo Liu,Xueyou Qin,Weiqi Chen,Jin Zhang,Songgu Wu,Junbo Gong
Punch sticking during tablet manufacturing is a prevalent issue for many active pharmaceutical ingredients (APIs) encountered by the pharmaceutical industry. Tenofovir amibufenamide fumarate (TMF), a heavyweight drug for the treatment of hepatitis B, was selected as a model drug due to its tendency to punch sticking during tablet compression. In this study, the cause of sticking was explored by investigating crystal habits, excipients and structure characteristics. The difference in sticking of three crystal habits can be visually represented through direct compression experiments on powdered samples and analysis of crystal surfaces. The excipients play a direct role in decreasing the probability of sticking, and the extent of sticking can be assessed by measuring the tensile strength of the tablet. Additionally, the plasticity index was utilized to theoretically analyze the potential enhancements of four excipients. These experimental results indicate that the block-shaped crystals have superior ability of anti-sticking and that suitable excipients can significantly improve the sticking situation of TMF. Ultimately, the phenomenon of punch sticking was additionally examined through computational calculations, focusing on the mechanical characteristics of TMF molecules and intermolecular interactions. The strategy of combining experiments and simulation calculations has broader significance for the study of drug production.
研究领域:
药剂学
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药物制造
·
计算化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Xianhui Cheng,Yujuan Miao,Juntao Zhou,Feng Lu,Jingji Jin,Lianghai Hu
Plasma membranes not only maintain the intracellular microenvironment through their phospholipid bilayer but also eliminate exogenous compounds outside the cell membranes. Most drugs especially with high polarity are prevented from entering into cells to exert their effects. Therefore, it is of great significance to design effective drug carriers with a penetrating ability toward plasma membranes. In this study, a dual-templated MIP (dt-MIPs) carrier with controllable microstructure and high drug loading capacity was prepared using highly expressed sphingomyelin on the plasma membrane and tenofovir (TFV), a first-line drug for HIV and chronic hepatitis B, as template molecules. The drug release experiments performed in vitro under simulated physiological conditions demonstrated that sustained and stable adsorption of TFV on dt-MIPs was more than 80% over 50 h. By a combination of flow cytometry and confocal microscopy, dt-MIPs were found to have efficient cell permeability. Furthermore, mass-spectrometry-based intracellular pharmacokinetic studies demonstrated that TFV was delivered completely into cells within 30 min with the delivery of dt-MIPs. The study presented above suggested that dt-MIPs are expected to be alternative nanoscale drug carriers for enhanced drug permeability and controlled release.
研究领域:
药学
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纳米技术
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药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHROMATOGRAPHIA
·
2023
·Vol. 86
·期 3
·213-222
·
IF 1.7
Lin Li,Huang Lingyi,Ke Yanbing,Xu Xiaowen,Huang Liying
This study aims at developing a high-performance liquid chromatography–mass spectrometry (LC–MS) method to analyze tenofovir disoproxil fumarate (TDF) and its pharmaceutical preparations. Several cyclodextrin mobile-phase additives were applied to reversed-phase and normal-phase chromatography, and the effects of three chiral stationary phases on the TDF separation were investigated in this study. The R-type and S-type of TDF tablets were quantitatively analyzed in the single ion monitoring (SIM) scanning mode with a Unichiral CMD column. This method has been successfully applied to the separation and quantification of TDF and its isomers. The linear ranges of (R)-TDF and (S)-enantiomer were 1–20 and 0.2–16 μg/mL, respectively. The limit of detection for (R)-TDF and (S)-enantiomer was 0.0015 and 0.0012 μg/mL, respectively. (S)-enantiomer was not detected in the formulas from all the seven manufacturers, and the drug content of each took more than 98.5% of the labeled amount, which complies with the regulations. The method shows its advantages on high sensitivity, low detection limit, good practicability, and repeatability. The proposed method may provide a novel platform for separation of TDF enantiomers and quality control of TDF raw materials and preparations.
研究领域:
分析化学
·
药学
·
色谱学
·
质谱学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Yanbo Liu,Xiaolei Wang,Chenyang Zhao,Shuo Wang,Xiaogang Lian,Weiqi Chen,Lei He,Mingyang Chen,Songgu Wu,Junbo Gong
Tenofovir amibufenamide fumarate (TMF) is the first oral drug developed in Asia for the treatment of adult patients with chronic viral hepatitis B, however, further applications are limited by poor tableting performance and high sticking propensity. In this work, the spherulitic growth process of TMF has been designed and explored with the help of molecular dynamics simulation and process analysis technologies (ATR-FTIR, FBRM and EasyViewer). The spherical particles with high bulk density, good flowability and uniform particle size distribution are prepared by a simple quenching process. More importantly, experimental results show that spherical particles have higher average tensile strength (100.8% increase), higher plastic deformability and lower amount of punch sticking (87.4% decrease in 30 tablets) compared to the commercial powder products. These contributions not only shed light on the design principle of drug spherulitic growth processes, but also provide guidance for the manufacture of high-quality tablet products.
研究领域:
药学
·
结晶工程
·
材料科学
·
药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
·
2017
·Vol. 132
·期 1
·471-482
·
IF 1.953
Wu Cheng-jie,You Jin-zong,Wang Xue-jie
Tenofovir disoproxil fumarate (TDF) is an antiretroviral medication widely used to prevent and treat HIV/AIDS and to treat chronic hepatitis B. In this paper, thermal decomposition processes of TDF were measured with thermogravimetry, differential scanning calorimetry and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy. The IR spectra, high-performance liquid chromatography and liquid chromatography mass spectrometry of TDF and the residues of its thermal decomposition at various temperatures were determined. The molecular bond orders were calculated using an ab initio method from the GAMESS program of quantum chemistry. The mechanism of thermal decomposition was discussed. The results indicated that the thermal decomposition of TDF is a three-step process, the initial step of thermal decomposition of TDF is the decomposition of carboxylic ester, the first stage mainly is the decomposition of the phosphoric disoproxil section, and the second stage mainly is the decomposition of the tenofovir section and partially goes through adenine stage. The initial decomposition temperature in either nitrogen or air is 138 °C, and the thermal stability of TDF is not very good under routine temperature.
研究领域:
药物化学
·
物理化学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）