JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
·
IF 3.1
Zhao-liang Hu,Wen-yu Zou,Peng-wei Hu,Ke-ran Chen,Jia-ying Liu,Jie Deng,Ju-cui Yang,Min Song,Yu-ting Lu,Tai-jun Hang
Letrozole, a nonsteroidal aromatase inhibitor of the triazole class, is widely used in breast cancer treatment. Its quality and stability directly influence therapeutic efficacy and safety. However, systematic characterization of its related substances (RSs) remains insufficiently documented. In this study, letrozole RSs were separated by an established HPLC-UV method and identified with LC-Q-TOF/MS determination following the ICH Q1A(R2) guidelines. 27 RSs were detected, including 11 process-related impurities and 16 previously unreported degradation products. Structural elucidation and degradation pathway analysis were performed for all the RSs by using their chromatographic retention behaviors, DAD spectral features, and high-resolution mass spectrometric data. Three main degradation pathways were proposed for them, including substitution on the triazole ring, hydrolysis of the cyano groups, and oxidation of the benzyl moiety. Furthermore, to support impurity risk assessment, the genotoxicities of all the RSs were evaluated using in-silico models according to the ICH M7 (R2) guideline. Most of the RSs were evaluated to be non-mutagenic, however four of them were identified as structurally alerting. These findings contribute to a better understanding of the stability behavior of letrozole and provide a scientific basis for the drug quality risk management from its related substances test and control point of view.
研究领域:
药物化学
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分析化学
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药学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2022
·
IF 3.571
Jing Jiang,Zhao-liang Hu,Hamza Boucetta,Jia-ming Liu,Min Song,Tai-jun Hang,Yu-ting Lu
Flumazenil is an imidazobenzodiazepine derivative that antagonizes the actions of benzodiazepines . The degradation pathway elucidation plays an important role in the drug quality control. In this work, a reliable LC-Q-TOF/MS method was developed to separate and identify the degradation products of flumazenil generated in the stress testing conducted according to the ICH Q1A(R2) guideline. Fifteen degradation products were detected in total including three reported impurities and twelve unknown impurities. Based on the chromatographic and mass spectrometric data acquired, the structures of all the degradation products were identified. Besides, two major degradants were synthetized and further confirmed by NMR. The degradation pathways of flumazenil were elucidated, and the degradation characteristics of benzodiazepines were also discussed. The obtained results are of both great importance for the quality control of flumazenil and good reference for the degradation study of other benzodiazepines.
研究领域:
药物化学
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分析化学
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药学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2018
·Vol. 410
·期 18
·4311-4322
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IF 3.307
Wu Si-Qi,Song Hui-Peng,Li Bin,Liu Run-Zhou,Yang Hua,He Ling,Li Ping
Development of fast and accurate methods to discover lead compounds for drug candidates is highly important. In this study, a reliable and effective post-column on-flow biochemical assay (POBA) was established to screen potent peroxidase inhibitors from complex chemical mixtures (e.g., natural product extracts). Multiple factors such as flow rate, organic phase, detection wavelength, and reaction coil were carefully investigated. To better understand the features of POBA, another emerging technology of ultrafiltration LC-MS was used for comparison. The result showed that POBA had advantages in saving time, avoiding false positives, and improving the accuracy. To illustrate the practicality of the method, Radix Salvia Miltiorrhizae, a traditional herb for cardiovascular disease treatment, was applied as the research objective. Finally, six compounds including tanshinol, protocatechuic aldehyde, salvianolic acid D, rosmarinic acid, lithospermic acid, and salvianolic acid B were determined as novel peroxidase inhibitors. Their bioactivities were validated by microplate-based assay, molecular docking, and pharmacophore modeling. This study demonstrates a great potential of POBA in the efficient and accurate discovery of drug candidates.
Compared with a classical method of ultrafiltration LC-MS, the newly developed method of on-flow bioassay shows advantages in saving time, avoiding false positives and improving the accuracy
研究领域:
药理学
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分析化学
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天然产物研究
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2023
·
IF 3
Yue-Hua Chen,Si-Yu Li,Dan Wang,Wei Yuan,Kun Xu,Jia-Wei Wang,Ting-Guo Kang,Hui Zhang
Marsdenia tenacissima is a traditional Chinese medicinal plant used for treating cancer, and its main medicinal part is the stem. Considering the resource shortage of M. tenacissima , it is of great significance to improve its utilization efficiency. Steroids and caffeoylquinic acids, the two main components of M. tenacissima , are composed of several basic structures. Based on this rule, a novel strategy of combinatorics-based chemical characterization was proposed to analyze the constituents of roots, stems and leaves of M. tenacissima . Combinatorics was used to generate a compound library for structure alignment, which has the advantages of wide coverage and high specificity. Steroids are composed of four basic parts: core skeleton (C), substituent at position 11 (A), substituent at position 12 (B) and sugar moiety (S). Based on combinatorics, a compound library consisting of 1080 steroids was generated. Diagnostic neutral loss has been used to effectively predict the substituents at position 11 and 12 of steroids, including acetyl, 2-methylpropionyl, tigloyl, 2-methylbutyryl and benzoyl. As a result, 131, 131 and 99 components were detected from the roots, stems and leaves of M. tenacissima , respectively. Principal component analysis (PCA) was used to analyze the differences of roots, stems and leaves, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was further applied to find differential components. Tenacissoside H, a critical indicator component for quality evaluation of the stem, has been proved to be a differential component between roots and stems. Notably, the relative content of tenacissoside H in the roots was significantly higher than that in the stems. The bioactivity comparison showed that roots, stems and leaves of M. tenacissima had similar scavenging activity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. However, their α-glucosidase inhibitory activity was ranked as leaves > stems > roots. Therefore, besides stems, the other parts of M. tenacissima have potential medicinal value. This study not only helps to develop the resource of M. tenacissima , but also provides a paradigm for the research of other similar medicinal plants.
研究领域:
药用植物学
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分析化学
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中药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2021
·
IF 3.205
Hua Guo,Yue-Hua Chen,Tian-Min Wang,Ting-Guo Kang,Hui-Yang Sun,Wen-Han Pei,Hui-Peng Song,Hui Zhang
The lack of direct connection between traditional herbal medicines and multiple biological targets is a bottleneck in herbal research and quality evaluation. To solve this problem, a strategy for the discovery of active ingredients from function-similar herbal medicines based on multiple biological targets was proposed in this article. The technical route includes chromatographic separation, mass spectrometry analysis, enzymatic activity detection, pharmacophore analysis and molecular docking. Five citrus herbs of Citri Reticulatae Pericarpium (CRP), Citri Exocarpium Rubrum (CER), Citri Grandis Exocarpium (CGE), Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) were used as the research objects. A total of 136 chemical components were identified from above five herbs based on LC-Q-TOF-MS/MS and database matching. The extracts of the five herbs showed obvious inhibitory effects on α-glucosidase and acetylcholinesterase in a concentration-dependent manner. Interestingly, the different types of components in the herbs exhibited selectivity for different targets: flavanone glycosides are effective on α-glucosidase but ineffective on acetylcholinesterase; polymethoxyflavonoids are effective on acetylcholinesterase but ineffective on α-glucosidase. Furthermore, we found for the first time that the components in citrus herbs exhibit opposite structure-activity relationships on the above two targets. For example, the methoxy group can enhance the activity of compounds on acetylcholinesterase but weaken the activity of compounds on α-glucosidase. The selective action is a supplement to the “multi-components, multi-targets” system of herbal medicines. Pharmacophore analysis and molecular docking were applied to explore the interaction between active ingredients and biological targets from the perspective of ligands and receptors, respectively. By combining the above multiple technologies, a strong connection among herbal medicines, chemical components and multiple biological targets was established. This work not only helps to understand the similar function of citrus herbs for the treatment of diabetes and Alzheimer's disease, but also provides selective lead compounds for the development of related drugs. This strategy is also helpful to improve the quality evaluation of citrus herbs from the perspective of biological activity.
研究领域:
药理学
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分析化学
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中药学
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分子生物学
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药物发现
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产品关联
DOI
PubMed
高影响因子
CURRENT DRUG METABOLISM
·
2023
·
IF 2.3
Zhou Shuhan,Song Xiaoting,Fang Pengkai,Xu Jingyi,Liu Siqi,Zheng Tian,Wu Guoping,Wu Liang
Background: Benzodiazepines (BZDs) are compounds that contain one diazepine ring and two benzene
rings, and are widely used to treat central nervous system diseases. However, drug abuse and BZDs' illegal addition
may affect normal life and even lead to grave social harm. As BZDs may be metabolized and eliminated quickly, it is
of great theoretical and practical significance to clarify their metabolic profile.
Objective: In this paper, LC-Q-TOF/MS-based fragmentation behavior has been investigated for nine benzodiazepine
drugs available and widely used in clinical treatment (diazepam, nitrazepam, clonazepam, oxazepam, lorazepam,
alprazolam, estazolam, triazolam, and midazolam), and their metabolic profile has been studied by using in vitro
human liver microsomal incubation.
Methods: A regular human liver microsomal system was used to investigate the potential biotransformation of the
nine benzodiazepines in vitro, and an LC-Q/TOF-MS was used to perform fragmentation behavior studies and metabolite
identification.
Results: As a result, characteristic fragmentation pathway and diagnostic fragment ions of the nine BZDs were analyzed,
and 19 metabolites of the 9 benzodiazepines were found and identified, with glucuronidation and hydroxylation
considered as their most important metabolic pathways.
Conclusion: These experimental data add to our knowledge of the nine benzodiazepine drugs and their metabolism
study, which could provide useful information and evidence of their in vivo metabolic profile prediction and help
promote their monitoring in both clinical use and social/illegal abuse.
研究领域:
药理学
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分析化学
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毒理学
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药物代谢
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Junji Wu,Yanpeng Gao,Yaxin Qin,Guiying Li,Taicheng An
Recently, fragrance ingredients have attracted increasing attention due to their imperceptible risks accompanying the comfortable feeling. To understand transformation mechanisms and toxicity evolution of benzyl formate (BF) in environment, its photochemical degradation in water was thoroughly studied herein. Results showed that 83.5% BF was degraded under ultraviolet (UV) irradiation for 30 min. Laser flash photolysis and quenching experiments demonstrated that triplet excited state ( 3 BF*), O 2 •− , and 1 O 2 were three main reactive species found during BF photodegradation. Eight degradation intermediates, including benzaldehyde, benzyl alcohol, o-cresol, bibenzyl, benzyl ether, 1,2-diphenylethanol, benzoic acid, and benzylhemiformal, were mainly formed as identified by LC-Q-TOF/MS and GC-MS analyses. Furthermore, the degradation mechanism was explained as the bond cleavage of 3 BF* and BF •+ , O 2 •− / 1 O 2 oxidation, e aq − reduction, and • OH addition reactions. Aquatic assessment suggests that except benzyl alcohol, benzoic acid, and benzylhemiformal, all the products were persistent and could result in increased aquatic toxicity compared to original BF. Consequently, these degradation products may cause more toxicity to organisms if they remain accumulated in water environment for a long time.
研究领域:
环境化学
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毒理学
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分析化学
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DOI
PubMed
高影响因子
ACS Omega
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2020
·
IF 2.87
Yilong Liu,Xianan Zhang,Liuhuan Zhan,Chang Xu,Linxiao Sun,Huamin Jiang,Chongde Sun,Xian Li
The present study is to investigate the polyphenolic composition and in vivo antidiabetic effect of white-fleshed Chinese bayberry cultivar “Shui Jing”. By liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS), 38 polyphenols were identified in the Shui Jing fruit extract (SJE), where proanthocyanidins (PAs), including epigallocatechin gallate (EGCG), as well as flavonols, including myricitrin and quercetrin, were the predominant ingredients. After a 5-week experiment, the SJE (200 mg/kg bodyweight) significantly reduced fasting blood glucose, elevated glucose tolerance, and insulin sensitivity in diabetic KK-Ay mice. It markedly attenuated bodyweight gain and decreased glycolipid metabolism-related markers including insulin, leptin, glucagon, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and alanine aminotransferase (ALT) levels in mice. Liver weight and hepatic lipid accumulation were also significantly reduced by the SJE. Gene expressions of insulin 1 (INS1) and glycogen synthase kinase 3 β (GSK3b) were markedly inhibited while the hepatic phosphorylation of AMPKα was significantly increased in the liver of SJE-treated mice, indicating that the SJE may exert an antidiabetic effect through an AMPK-dependent pathway. In conclusion, white bayberry rich in PAs and flavonols may have great potential in the regulation of diabetes mellitus.
研究领域:
药理学
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营养学
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分子生物学
·
糖尿病研究
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2026
·Vol. 16
·期 15
·13572-13584
·
IF 6.1
Yirang Wang,Zhongquan Li,Jiahui Cheng,Tingyuan Zheng,Peijie Chen,Xiaojun Deng,Pei-chao Zhang,Bing Liu
5α Reductase inhibitors (finasteride and dutasteride) have been classified as monitored substances by the World Anti-Doping Agency (WADA) due to their potential abuse as masking agents for anabolic-androgenic steroids. As a member of the same class of inhibitors, epristeride shares a similar pharmacological mechanism of action and thus poses an inherent risk of abuse. However, current research on the metabolic characteristics of epristeride remains limited, which hinders its effective monitoring in anti-doping practices. In this study, a zebrafish model combined with liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF MS) was employed to systematically investigate the metabolic transformation of epristeride in vivo. Additionally, omics analysis was utilized to elucidate the effects of epristeride administration on endogenous metabolic pathways. A total of 11 epristeride metabolites were successfully identified, including 4 phase I metabolites and 7 phase II metabolites, primarily involving metabolic reactions such as oxidation, methylation, and glucuronide conjugation. Omics analysis revealed that N,N-dimethyldecylamine oxide (DDAO) with an AUC value of 0.80 could serve as a potential biomarker. Pathway enrichment analysis indicated that epristeride significantly perturbed purine metabolism and aromatic amino acid biosynthesis. These findings provide a more precise understanding of the metabolic fate of epristeride in organisms, offering a scientific basis for the development of accurate detection methods.
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Lulu Chen,Xiaona Dong,Ruonan Feng,Wanying Li,Dahu Ding,Tianming Cai,Canlan Jiang
Triclosan (TCS) is a compound in pharmaceutical and personal care products (PPCPs) that preferentially accumulates in soil and may threaten human health. Iron-based persulfate activation processes (Fe-PAPs) are a promising technique in soil remediation but are limited by their narrow pH application range and resultant iron precipitation. In this study, oxalic acid (OA) was specifically introduced to improve the efficiency of Fe 2+ -activated persulfate (PS) processes for TCS degradation in soil. The complexation of OA and Fe 2+ improved the total iron concentration in the Fe 2+ /OA/PS system and prevented iron precipitation. Fe-minerals in soil were also dissolved by OA, which participated in PS activation. The most appropriate proportion of Fe 2+ /OA/PS is 1:1:1, and approximately 85% of the TCS was degraded within 240 min compared with 45% in the Fe 2+ /PS system. SO 4 • - and 1 O 2 played important roles on TCS oxidation, while O 2 • - and CO 2 • - mainly participated in the iron cycle. The weak stretch of Fe-O in OA containing treatments in ATR-FTIR measurements provided evidence that OA dissolved the Fe-minerals. The introduction of OA in the Fe 2+ /PS system in four different soils reduced the negative effect of soil organic matter on TCS degradation. Three types of intermediates including hydroxylation, cleavage of ether bonds and cyclization products, were identified by LC-Q-TOF-MS. Column experiments were used to study the feasibility of in situ chemical oxidation (ISCO) remediation of TCS in the Fe 2+ /OA/PS system. Our findings indicated the ability of OA to be used as a cheating agent in Fe-PAPs for TCS soil remediation.
研究领域:
环境科学
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土壤化学
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污染物降解
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修复技术
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产品关联
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Lulu He,Jianqin Qian,Peixi Zhu,Weifeng Yang,Yuanbin She
A simple and sensitive method was developed for separation and characterization of seventeen impurities from commercial latamoxef sodium for injection by liquid chromatography combined with electrospray ionization and QTOF mass spectrometer (LC-ESI-QTOF MS). The chromatographic separation was performed on a Boston Green ODS-AQ C18 column (250 mm × 4.6 mm, 5 μm) under gradient mode using binary mobile phase: (A) ammonium acetate (10 mM)-methanol (99:1, v/v) and (B) ammonium acetate (10 mM)-methanol (70:30, v/v). Based on tandem multistage MS and high resolution MS data, the molecular formulas and structures of unknown impurities were inferred. A plausible formation mechanism of impurities was also proposed. In addition, the fragmentation regularity of degraded impurities in positive-ion mode was summarized.
研究领域:
分析化学
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药物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Qu Zhang,Chao Xue,Gary Owens,Zuliang Chen
The widespread presence of 17β-estradiol (E2) in the environment is an emerging problem because it poses a potential threat to human health and aquatic organisms. In this study, a strain of E2 degrading bacteria was isolated from activated sludge . 16s rRNA analysis combined with physiological and biochemical detection confirmed that the bacterium was Ochrobactrum sp. strain FJ1. At an initial E2 concentration of 15 mg L −1 , strain FJ1 degraded 98 ± 1% of E2 after 10 days. Furthermore, when methanol was added as an additional carbon source, the biomass of strain FJ1 increased by 35 ± 1%, and E2 degradation efficiency was slightly inhibited. Compared with E2 alone when glucose, sodium acetate, and methanol were added as additional carbon sources, biomass decreased by 20 ± 1, 13 ± 1 and 35 ± 1%, respectively. Analysis of the degradation products of E2 by LC/Q-TOF-MS confirmed that the major degradation products of E2 were estrone (E1) and 4,16-OH-E1, which was further degraded by strain FJ1 to several other unknown compounds. Based on SEM and FTIR analysis, the morphology of the bacteria became thicker and the thickness of the cell walls decreased under initial E2 stress, and thereafter E2 was transported into the bacteria primarily via several proteins on the cell surface. Considering the ability and efficiency of Ochrobactrum sp. strain FJ1 to degrade high E2 content, the strain could provide a new bioremediation technology for the effective biodegradation of E2. Finally, a potential bioremediation pathway of E2 by Ochrobactrum sp. strain FJ1 was proposed.
研究领域:
环境科学
·
微生物学
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生物技术
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）