Current Pharmaceutical Analysis
·
2023
·Vol. 19
·期 6
·511-520
·
IF 0.6
Zhang Mengmeng,Zou Qiaogen
Background: Atopic dermatitis (AD) is an allergic skin disease that can be inherited. Crisaborole is a specific drug developed to deal with this disease. The compounds of 4-(4- Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4-bromo-3-formylphenoxy)-3- formylphenoxy) benzonitrile
are the representative impurities in the synthesis of Crisaborole active pharmaceutical in gradient (API). Owing to the genotoxic impurities that could lead to cancer and gene mutations, it is necessary to develop a simple, efficient, sensitive, and accurate method to detect these impurities.
In this study, the 4-(4-Bromo-3-formyl-phenoxy)-benzonitrile and 4-(4-(4- bromo-3-formylphenoxy)-3-formylphenoxy)benzo- nitrile present in Crisaborole API were detected using UPLC-MS/MS. Methods: The separation was made on a ZORBAX Eclipse XDB-Pheny column (4.6 mm ×75mm, 3.5
μm) with the mobile phase of acetonitrile solution containing 0.1% trifluoroacetic acid (A) and water containing 0.1% formic acid (B) in gradient elution mode. Quantification was performed using positive ion electrospray ionization (ESI), and the contents of two compounds were determined
using the multiple reaction monitoring (MRM) modes. Results: The quantitative analytical method was fully validated with respect to linearity (r > 0.9998), sensitivity, precision, accuracy (the average recovery of two impurities was 84.1% to 90.7%), and robustness. Conclusion:
Three batches of samples were detected by UPLC-MS/MS, indicating that the proposed approach was applicable for the quality evaluation of Crisaborole.
研究领域:
药物分析
·
皮肤病学
·
毒理学
✓ 已验证
DOI
高影响因子
FUEL PROCESSING TECHNOLOGY
·
2016
·
IF 3.847
Mei-Xia Zhao,Xian-Yong Wei,Meng Qu,Zhan-Ku Li,Jing Liu,Yan Li,Jiao Kong,Wei Zhao,Zhi-Min Zong
A novel solid acid was prepared by impregnating trifluoromethanesulfonic acid (TFMSA) onto attapulgite powder (AP). Benzyloxybenzene (BOB) was used as a lignite-related model compound to evaluate the catalytic activity of TFMSA/AP for cleaving C alk –O bridged bonds in lignites. The results show that BOB was mainly hydrocracked to toluene, phenol , and (ethoxymethyl)benzene over TFMSA/AP in ethanol without adding gaseous hydrogen. In addition, ethanol participated in and significantly facilitated BOB hydrocracking . Based on the kinetic investigation, BOB hydrocracking over TFMSA/AP is absent of mass transfer limitations with the apparent activation energy of only 19.4 kJ mol − 1 , which is far smaller than the dissociation energy (209.2 kJ mol − 1 ) of C alk –O bridged bond in BOB. The proton transfer directly from TFMSA/AP and/or via ethanol dehydrogenation to the oxygen atom of BOB could be the crucial step for BOB hydrocracking over TFMSA/AP.
研究领域:
化学工程
·
催化科学
✓ 已验证
产品关联
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Yiwen Cui,Yingying Sun,Hang Yu,Yahui Guo,Weirong Yao,Yunfei Xie,Fangwei Yang
Pyrethroid insecticides (PIs), a class of structurally similar non-persistent organic pollutants, can be degraded and metabolized to more toxic, and longer half-life products. In this study, the binding interaction mechanisms between human serum albumin (HSA) and the main degradation metabolites of PIs, 3-phenoxybenzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), were studied by theoretical simulation and experimental verification. Steady state fluorescence spectra showed that the fluorescence quenching mechanism was static. According to the binding constant, 4-F-3-PBA (1.53 × 10 5 L mol −1 ) was bound more strongly to HSA than 3-PBA (1.42 × 10 5 L mol −1 ) in subdomain ⅡA (site I). It was found by isothermal titration calorimetry that the metabolites and HSA spontaneously combined mainly through hydrogen bond and van der Waals interaction . Ultraviolet absorption spectra and circular dichroism spectra showed that the metabolites caused slight changes in the microenvironment and conformation of HSA. The above results were proved by molecular docking. The toxicity properties of the metabolites were further analyzed by software, and 4-F-3-PBA was found to be more toxic than 3-PBA. Considering the high exposure level of these metabolites in food , the environment and human body, it is necessary to further explore the toxicity of PIs metabolites.
研究领域:
环境科学
·
毒理学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL MANAGEMENT
·
2022
·
IF 8.91
Kaidi Hu,Jianlong Li,Tianye Zhao,Qiao Zhou,Qin Li,Xinjie Hu,Guoquan Han,Shuhong Li,Likou Zou,Shuliang Liu
As a major intermediate metabolite of synthetic pyrethroids , the occurrence of 3-phenoxybenzoic acid hinders the decomposition of the parent pesticide and poses uncertain risks to environmental ecology and living organisms. Strain Aspergillus oryzae M-4 was previously reported to degrade 3-PBA and several substances were identified as downstream transformation products (TPs). But the mechanism underlying the cleavage of ether bond remains largely unclear. Here, we attempted to address such concern through identifying the peripheral TPs and analyzing transcriptomics, coupled with serial batch degradation experiments. Analysis results of chromatographic/mass spectrometry suggested that 3-PBA underwent twice hydroxylation , to yield mono- and dihydroxylated 3-PBA successively. In parallel, a mutual transformation between 3-PBA and 3-phenoxybenzyl alcohol (3-PBOH) also existed. The proposal of peripheral pathway represents an important advance towards fully understanding the whole 3-PBA metabolism in M-4. A specific altered metabolization was found for the first time, that is, resting cells of M-4 skipped the reduction step and initiate hydroxylation directly, by comparison with growing cells. Transcriptome analysis indicated that 3-PBA induced the up-regulation of genes related to energy investment, oxidative stress response, membrane transport and DNA repair. In-depth functional interpretation of differential expression genes suggested that the generation 3-PBOH and hydroxylated 3-PBA may be due to the participation of flavin-dependent monooxygenases (FMOs) and cytochrome P450 (CYP450), respectively. This study provides new insight to reveal the biodegradation mechanism of 3-PBA by A . oryzae M-4.
研究领域:
环境科学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2017
·
IF 5.099
Xiaoqing Ye,Wuye Pan,Yuehao Zhao,Shilin Zhao,Yimin Zhu,Weiping Liu,Jing Liu
Pyrethroids , a class of ubiquitous insecticides, have been considered as endocrine-disrupting chemicals (EDCs). Female animal studies suggested that early-life pyrethroids exposure might delay puberty onset. However, it remains unclear whether this association applies to human populations. A total of 305 girls at the ages of 9–15 years old were recruited in Hangzhou, China in this study. The concentration of the common metabolite of pyrethroids, 3-phenoxybenzoic acid (3-PBA), was analyzed in urine samples to reflect the exposure level of pyrethroids. The associations of 3-PBA with pubertal stages were evaluated using a multinomial logistic regression model. The geometric mean level of 3-PBA was 1.11 μg/L (1.42 μg/g for creatinine-adjusted concentration). There was a significant 45% reduction in odds of being in breast stage 3 (B3) per one-unit increase in the log-transformed 3-PBA levels [OR = 0.55 (95%CI: 0.31–0.98), p = 0.042]. A similar negative association was found between urinary 3-PBA levels with later onset by pubic hair stage 2 (P2) [OR = 0.56 (95%CI: 0.36–0.90), p = 0.015]. Similar negative association was also observed between urinary 3-PBA levels and pubertal onset indicated by menarche [OR = 0.51 (95%CI: 0.28–0.93), p = 0.029]. For the first time to our knowledge, this work reveals that pyrethroids exposure may increase the risk of delayed pubertal onset in girls.
研究领域:
环境科学
·
公共卫生
·
生殖健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2020
·Vol. 137
·期 31
·48919
·
IF 2.52
Ting Guo,Hongyuan Zhou,Yong Yu,Hongjie Dai,Yuhao Zhang,Liang Ma
A novel recognition material for detection of kinds of pyrethroids was successfully synthesized by molecular imprinting technology. 3-Phenoxybenzoic acid (PBA) usually could be the antigen to prepare the polyclonal antibody. In this work, the recognition material was prepared utilizing PBA as the template, methacrylicacid as the functional monomer and ethylene glycol dimethacrylate as the crosslinker. The recognition material was characterized by atomic force microscope, adsorption equilibrium and selectivity experiments. The results showed that the recognition material has been successfully prepared and recognized four pyrethroids (fenpropathrin, deltamethrin, fenvalerate, and cyhalothrin). The recognition material was utilized as sorbents in solid-phase extraction for separation and detection of pyrethroids in practically samples. Under the optimal conditions, the recoveries were ranging from 74.3 to 111.0%. Therefore, novel materials for pyrethroids are very promising for future applications. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137 , 48919.
研究领域:
分析化学
·
环境科学
·
农药检测
✓ 已验证
DOI
高影响因子
HIGH PERFORMANCE POLYMERS
·
2021
·
IF 2.161
Kai Ma,Hanzhou Jiang,Guofei Chen,Wei Wang,Yonggang Zhang
Several polyimides were prepared via two-step polycondensation from novel 2,5-furandicarboxylic acid–based diamine, 2,5-bis[4-(4-aminophenoxy)benzoyl]furan, with commercial dianhydrides. The chemical structures of the monomers and polymers were characterized by FT-IR and NMR in detail, respectively. The polyimides exhibited high performances with 5 wt% weight loss temperatures of over 410 oC, glass transition temperatures of over 214 oC, and tensile strengths and Young’s moduli of up to 130 MPa and 3.2 GPa, respectively. The thermal crosslinking mechanism was studied by FT-IR, Raman spectroscopy, and model reaction analysis, which showed the Diels–Alder reaction between the furan group and diphenylethylene group was the main reaction. The crosslinked polyimide films showed improved solvent resistance, and thermal and mechanical properties.
研究领域:
材料科学
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Li Ming,Yongfei Zhou,Ning Li,Xinhua Zhou,Hongyan Zhang,Xiaobo Zou,Can Zhang
The integration of nanobody and nanozyme has emerged as a transformative strategy in immunoassays, offering enhanced sensitivity, stability, and versatility compared to conventional antibody-enzyme conjugates. Herein, we successfully developed a ternary nanostructure by integrating silica nanoparticles (SNPs), polydopamine (PDA), and platinum nanoparticles (Pt NPs), yielding SNPs@PDA@Pt (SPP) with robust nanozyme catalytic activity. Notably, the SPP was surface-modified with polyethyleneimine (PEI) to generate positively charged PEI-modified SNPs@PDA@Pt (PSPP). This modification substantially improved the coupling efficiency with anti-3-phenoxybenzoic acid nanobodies (3-PBA Nbs) via electrostatic interactions. The PSPP-based coupling achieved a remarkable efficiency of 92.28 %, representing about a 4.5-fold increase over the SPP method (20.55 %). The PSPP@3-PBA Nbs nanocomposite was successfully integrated into both ELISA and LFIA platforms, achieving remarkable detection limits (0.001 ng/mL for ELISA and 0.003 ng/mL for LFIA). The nanocomposite also showed excellent stability, with no significant loss of immunobinding capacity or catalytic activity over 30 days. This work presents a novel design strategy for constructing high-performance nanozyme-nanobody nanocomposites, which shows great promise for ultra-sensitive 3-PBA detection in resource-limited settings.
研究领域:
免疫学
·
分析化学
·
纳米医学
·
环境毒理学
·
生物传感器
·
分子诊断
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-11
·
IF 3.998
Wang Yue,Xiao Han,Yang Lei,Jia Xiaojing,Guo Xuan,Zhang Zhaobin
p -Alkoxyphenols (AOPs) are a class of ethers that are widely used in industrial and agricultural productions and daily necessities. p -Phenoxyphenol (PhOP) and p -pentyloxyphenol (PeOP) belong to this class and have been reported to be estrogenic in vitro. However, their in vivo estrogenic activities have rarely been of concern. In this study, we performed an immature mouse uterotrophic assay and studied the estrogenic effects of these two compounds in mice. The results revealed that the uterine weights of the animals treated with PhOP significantly increased at doses of 30 and 300 mg kg -1 bw day -1 for 3 days ( P < 0.05), while no significant uterotrophic effects were observed in the mice treated with PeOP. Using next-generation transcriptome sequencing (RNA-seq), we also analyzed the gene expression in the uterine tissue of mice treated with PhOP and PeOP. The observed gene regulation patterns of the PhOP- and PeOP-treated specimens were similar to those of the 17 β -estradiol (E 2 )-treated specimens. In particular, some estrogen-responsive genes, such as the Sprr2 gene family, Apoa1 , Prap1 , and Ahsg , displayed a regulation trend similar to that of E 2 . In addition, molecule docking analysis revealed that both PhOP and PeOP could be well docked into the active site of hERα, with potential of mean force (PMF) values of − 58.68 and − 52.67 kcal mol -1 for PhOP and PeOP, respectively. The results of this study indicate that PhOP exhibits relatively strong in vivo estrogenic activity, which could be of future concern.
研究领域:
毒理学
·
分子生物学
·
内分泌学
✓ 已验证
DOI
PubMed
高影响因子
ACS Agricultural Science & Technology
·
2022
·
IF 0
Can Zhang,Jinnuo Hu,Xiaoxiao Wu,Jiyong Shi,Bruce D Hammock
As a major metabolite of pyrethroid pesticides, 3-phenoxybenzoic acid (3-PBA) can be an indicator of health risk and human exposure assessment. A gold–platinum (Au@Pt) nanozyme is a kind of mimic enzyme with unique properties of nanomaterials and catalytic activity. The anti-3-PBA nanobodies were labeled with Au@Pt (Au@Pt-Nbs) by electrostatic adsorption. The Au@Pt-Nbs lateral-flow nanozyme immunoassay was established for the visual and rapid detection of 3-PBA. The visualization results were quantitatively analyzed by Adobe Photoshop CC and got a cutoff value of 0.005 ng/mL. The samples of milk- and lake water-spiked 3-PBA were also analyzed, and the recoveries ranged from 102 to 108% and 95 to 112%, respectively. The results were also validated by liquid chromatography–mass spectrometry and got good correlation (R2 = 0.945). The Au@Pt-Nbs lateral-flow nanozyme immunoassay was developed by the combination of nanobodies and nanozymes, which will be a promising application in the field of safety inspection.
研究领域:
分析化学
·
环境科学
·
食品安全
·
纳米技术
✓ 已验证
DOI
Analytical Methods
·
2021
·Vol. 13
·期 14
·1757-1765
·
IF 2.896
Can Zhang,Xiaoxiao Wu,Dongyang Li,Jinnuo Hu,Debin Wan,Zhen Zhang,Bruce D. Hammock
As a major metabolite of pyrethroid pesticides, 3-phenoxybenzoic acid (3-PBA) can be an indicator of health risk and human exposure assessment. Based on nanobodies (Nbs), we have developed a rapid flow-through dot enzyme linked immunosorbent assay (dot ELISA) and gold nanoparticle (GNP) lateral-flow immunoassay for detecting 3-PBA. The limit of detection (LOD) values for detecting 3-PBA by flow-through dot ELISA and GNP lateral-flow immunoassay were 0.01 ng mL−1 and 0.1 ng mL−1, respectively. The samples (urine and lake water) with and without 3-PBA were detected by both nanobody-based flow-through dot ELISA and GNP lateral-flow immunoassay, as well as liquid chromatography-mass spectrometry (LC-MS) for validation. There was good consistency between the results of the immunoassays. This demonstrated that the two developed nanobody-based immunoassays are suitable for rapid detection of 3-PBA.
研究领域:
环境科学
·
分析化学
·
免疫学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）