BIOMEDICAL CHROMATOGRAPHY
·
2014
·Vol. 28
·期 10
·1393-1401
·
IF 1.662
Bin Deng,Zhi-Ming Wang,Zi-Hao Zhou,Yi-Meng Liu,Xi-Liang Yang,Jian Song,Yu-Xiu Xiao
Cellular heterogeneity in doxorubicin (DOX) uptake and its relationship with pharmacological effect on cancer cells were quantitatively investigated for the first time. An in vitro experimental model was established by treating human leukemia K562 and breast cancer MCF-7 cells with different schedules of DOX with or without surface P-glycoprotein (P-gp) inhibitor verapamil (VER). The cellular heterogeneity in DOX uptake was quantitatively examined by single-cell analysis using capillary electrophoresis coupled with laser-induced fluorescence detection. The corresponding cytotoxic effect was tested by cellular morphology, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium and flow cytometry assays. The expression of cellular membrane surface P-gp was determined by flow cytometry. Results showed that the cellular heterogeneity exists in DOX uptake. The single-high DOX schedule leads to lower uptake heterogeneity and higher mean drug uptake. The cellular heterogeneity in DOX uptake was found to be negatively correlated with drug cytotoxicity and surface P-gp expression, with r = −0.7680 to ~ −0.9587. VER reduces the cellular variation in DOX uptake, suggesting that surface P-gp may be one of the causes of the cellular heterogeneity in DOX uptake. This research demonstrates the importance of quantitative study of cellular heterogeneity in drug uptake and its potential application in drug schedule design, response prediction and therapy modulation. Copyright © 2014 John Wiley & Sons, Ltd.
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BIOMEDICAL CHROMATOGRAPHY
·
2014
·Vol. 29
·期 2
·312-320
·
IF 1.662
Jin Du,Maofang He,Xiaomeng Wang,Hua Fan,Yinmao Wei
The use of bronate affinity adsorbents is a new separation method that appeared recently with great potential for specific extraction of cis -diol-containing compounds. In this work,a new strategy for the facile construction of boronic acid-functionalized Fe 3 O 4 magnetic nanoparticles (Fe 3 O 4 @FPBA MNPs) with a high capacity was described. The extraction capacity of the Fe 3 O 4 @FPBA MNPs was determined to be 66.0 ± 2.7 µmol/g for catechol and 80.6 ± 2.0 µmol/g for dopamine, being higher than that for the reported methods. The Fe 3 O 4 @FPBA MNPs were used to extract four cis -diol drugs: caffeic acid isopropyl ester, caffic acid bornyl ester, isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate and 3-(3, 4-dihydroxyphenyl)-2-hydroxylpropionic acid – from the spiked rabbit plasma, and the recoveries of four drugs were between 87.29 and104.37% with relative standard deviations ranging from 1.34 to 8.81%. Under the most favorable conditions, the solid-phase extraction combined with HPLC-UV for the analysis of four drugs in plasma could eliminate interferences from endogenous components of the biological fluids and exhibited sufficient precision and accuracy. These results showed that the prepared Fe 3 O 4 @FPBA MNPs were qualified for efficiently enriching and determining the trace cis -diol substances from biological samples. Copyright © 2014 John Wiley & Sons, Ltd.
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BIOMEDICAL CHROMATOGRAPHY
·
2014
·Vol. 28
·期 10
·1325-1334
·
IF 1.662
Zhangxiao Peng,Yan Wang,Xue Gu,Xiaojie Guo,Chao Yan
A method based on high-performance liquid chromatography coupled with ultraviolet detection was developed for studying the pharmacokinetics of costunolide (Cos) and dehydrocostus lactone (Dehy) in rats after intravenous (i.v.) administration. Following i.v. administration, the maximum plasma concentrations of Cos and Dehy were observed to be 12.29 ± 1.47 and 5.79 ± 0.13 µg/mL, respectively. The bioavailability of Cos was larger than that of Dehy; however, the clearance and the volume of distribution of Dehy were much larger than those of Cos. An ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry system with automated MS E (E represents collision energy) data analysis software (MetaboLynx TM ) was used to analyze and identify the metabolites of Cos and Dehy in vivo . Four metabolites of Cos and six metabolites of Dehy were discovered from the plasma, urine and feces of rats. The main metabolic pathway of Cos was phase II biotransformation, but the main metabolic pathways of Dehy was phase І biotransformation. Two sequential desaturations and N -acetylcysteine conjugation were the common metabolic pathways of Cos and Dehy in rats. This information may be useful for the further development of the two drug candidates. Copyright © 2014 John Wiley & Sons, Ltd.
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BIOMEDICAL CHROMATOGRAPHY
·
2014
·Vol. 28
·期 12
·1738-1743
·
IF 1.662
Ling-ling Zeng,Li-li Sun,Qiaogen Zou,Fan Zhou,Ping Wei,Ping-kai Ouyang
Vilazodone hydrochloride (CAS 163521-12-8) is polymorphic and has 15 crystal forms, referred to as I–XI and XIII–XVI. In the study, we prepared and performed structural identification of a new crystal form named XVII. To investigate this in vivo , a rapid and sensitive method based on liquid–liquid extraction, followed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) was developed and validated for the determination of vilazodone hydrochloride in dog plasma. This HPLC-MS/MS method was successfully applied to a bioavailability comparison of two crystal forms of vilazodone hydrochloride (IV and XVII) in six healthy beagles using a single-dose, two-way crossover design. The maximum plasma concentration ( C max ), the time taken to reach C max , and the area under the concentration–time curve were determined following oral administration of 10 mg vilazodone hydrochloride (IV or XVII) to beagles. These analyses revealed no significant bioavailability differences between vilazodone hydrochloride forms IV and XVII in dogs. Copyright © 2014 John Wiley & Sons, Ltd.
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BIOMEDICAL CHROMATOGRAPHY
·
2014
·Vol. 29
·期 6
·860-868
·
IF 1.662
Xiaoping Zhang,Huiqing Lv,Zuguang Li,Kezhi Jiang,Maw-Rong Lee
Ficus pandurata H. aerial roots are used as a traditional Chinese medicine for the treatment of uarthritis, indigestion and hyperuricemia. However, the bioactive constituents responsible for the pharmacological effects of F . pandurata H. are unclear. A simple and efficient HPLC/QTOF-MS/MS (high-performance liquid chromatography/electrospray ionization with quadrupole time-of-flight tandem mass spectrometry) method was established to detect and identify active constituents in the n -butanol extract of F . pandurata H. aerial roots. Chemical constituents were separated and investigated by HPLC/QTOF-MS/MS in the negative-ion mode. Thirty-seven compounds, including hydroxycinnamic acid derivatives, hydroxybenzoic acid derivatives, hydroquinone glycosides, flavonoid glycosides, etc., were identified or tentatively characterized in the n -butanol extract of F . pandurata H. aerial roots by comparing the UV spectra, accurate mass spectra and fragmentation pathways and retrieving the reference literatures. Moreover, the flavonoid trisaccharides and hydroxybenzoic acid derivatives were tentatively characterized in F . pandurata H. for the first time. The analytical tool used here is very valuable in the rapid separation and identification of the multiple and minor constituents in the n -butanol extract of F . pandurata H. aerial roots. Copyright © 2014 John Wiley & Sons, Ltd.
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BIOMEDICAL CHROMATOGRAPHY
·
2017
·Vol. 31
·期 11
·e3997
·
IF 1.613
Yan Ren,Weiwei Zhao,Juanjuan Zhao,Xiangming Chen,Chen Yu,Mengan Liu
A simple, fast and reliable high-performance liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous quantification and pharmacokinetic study of three flavonoids (liquiritigenin, isoliquiritigenin and formononetin) and three anthraquinones (emodin, rhein and aloe-emodin), which are the bioactive ingredients of Wei-Chang-Shu tablet found in rat plasma. After extraction by liquid–liquid extraction with ethyl acetate, chromatographic separation was achieved on an Agilent Zorbax SB-C 18 column (4.6 × 150 mm, 5 μm) at a flow rate of 1 mL/min by gradient elution using 0.1% aqueous acetic acid and acetonitrile. The detection was performed using a triple quadrupole mass spectrometer equipped with electrospray ionization source in the negative ionization and selected reaction monitoring mode. Method validation was performed in terms of specificity, carryover, linearity ( r > 0.99), intra−/inter-day precision (1.0–10.1%), accuracy (relative error, <7.6%), stability (0.6–13.2%), extract recovery (74.9–91.9%) and matrix effect (89.1–109%). The lower limits of quantification of the six analytes varied from 0.92 to 10.4 ng/mL. The validated method was successfully applied to compare the pharmacokinetic properties of Wei-Chang-Shu tablet in normal rats and in rats with gastrointestinal motility disorders. The results indicated that there were obvious differences in the pharmacokinetic behavior between normal and model rats. This study will be helpful in the clinical application of Wei-Chang-Shu tablet.
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BIOMEDICAL CHROMATOGRAPHY
·
2024
·Vol. 39
·期 1
·e6055
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IF 1.8
Jianhui Luo,Songshen Chen,WenYang Song,Yongtong Huang,Song Gao,Jiu Wang
Ethoxysanguinarine (ETSG), a benzophenanthridine alkaloid, exhibits diverse biological activities, including antibacterial, antifungal, anti-inflammatory, antioxidant, and anti-tumor effects. Despite these properties, limited research exists on ETSG in vivo pharmacokinetics due to its poor solubility and low bioavailability. In this study, we developed a rapid and specific UPLC-MS/MS method for ETSG bioanalysis. Sample preparation involved one-step protein precipitation using methanol and phellodendrine as an internal standard (IS). The Waters HSS T3 column (2.1 * 50 mm, 1.8 μM) employed a gradient elution with mobile phases A (2 mmol/L ammonium formate aqueous solution-formic acid [99.8:0.2, v/v]) and B (methanol-formic acid [99.8:0.2, v/v]). Mass analysis via Waters Q-mass spectrometer utilized positive scan mode and multiple reaction monitoring. ETSG and IS were detected at m/z 332.0 → 274.0 and 342.0 → 177.0, respectively, within 7.0 min. The method demonstrated excellent precision, accuracy, recovery, and stability, with a linear calibration curve (1.1–560 ng/mL) and strong correlation coefficient (0.9984). Successful pharmacokinetic evaluation in Sprague–Dawley rats included intravenous ETSG administration and intragastric ETSG nanoemulsion/suspension. This method enables steroidal saponin analysis from ETSG in biological samples.
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BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6067
·
IF 1.7
Jiale Liu,Rongfei Yuan,Qi Wang,Hai Qiao,Yuling Yang,Siyu Yang,Hua Zhang,Chang Chen
High-intensity focused ultrasound (HIFU) is a noninvasive soft tissue ablation technique, which utilizes ultrasound energy to induce thermal coagulation necrosis in targeted tissues. Whether this high energy causes side effects in vivo, such as the formation of peptide bonds, has not been fully investigated. Glycylglycine is the simplest dipeptide and hence is often used as a model compound for peptide studies. In this study, we developed and validated a sensitive quantification method based on ion-exchange solid-phase extraction, liquid chromatography, and tandem mass spectrometry (SPE-LC-MS/MS) for the analysis of glycylglycine without derivatization, and then used it to evaluate whether HIFU promoted peptide bond formation in aqueous solution (without enzymes) and plasma (with enzymes). The results showed that strong cation exchange SPE significantly reduced the matrix effect and improved the sensitivity of the LC-MS/MS method. No formation of glycylglycine in the aqueous solution or plasma was observed following HIFU irradiation.
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BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6074
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IF 1.7
Qinghai Dong,Fei Shi,Fang Lin,Yaqi Wang,Yang An,Hongliu Xie,Jihua Liu
Previous studies have suggested that ginsenoside Rg 2 glycine ester derivative (RG) exhibits therapeutic potential in mitigating hypoxia. This study aimed to elucidate the potential mechanism of RG in hypoxia injury through a combined approach of metabolomics and network pharmacology. Initially, a CoCl 2 -induced cell hypoxia model was established, and the therapeutic impact of RG on biochemical indices was evaluated. Subsequently, metabolomics analysis of cell samples was conducted to identify biomarkers, and network pharmacology was employed to identify potential targets of RG for hypoxia treatment. Finally, the key target and pathway were verified. The study revealed that RG could reverse CoCl 2 -induced abnormalities in biochemical indicators. Metabolomics analysis identified 13 biomarkers and seven metabolic pathways associated with RG treatment. Utilizing network pharmacology, five key targets and five metabolic pathways were identified, partially aligning with the metabolomics results. Molecular docking results demonstrated the effective binding of RG to the key targets. Enzyme linked immunosorbent assay verified that RG could exert antihypoxia effect by activated PI3K/Akt pathway. In conclusion, this integrated strategy, combining metabolomics with network pharmacology, sheds light on the protective mechanism of RG against hypoxia-induced cellular damage. The findings offer valuable insights for future research and potential applications of RG in the field.
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BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6065
·
IF 1.7
Yong Jiang,Wenjun Ji,Ying Lu,Qin Wang,Linwei Chen
The high mortality rate of chronic heart failure (CHF) makes it a primary battlefield in the field of cardiovascular diseases. Qiangxin Lishui Prescription (QLP) is a traditional Chinese medicine (TCM) prescription used clinically for treating CHF, but its underlying mechanism remains unclear. This study integrated plasma metabolomics, network pharmacology, and experimental validation to reveal the pharmacological effects of QLP and its potential mechanism of anti-CHF. Using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS/MS), 119 absorbed prototype compounds of QLP were identified from rat plasma. By applying network pharmacology and molecular docking techniques, a QLP absorption components–target–CHF network was constructed. The IL6/JAK/STAT3 signaling pathway is likely critical to QLP's therapeutic effect on CHF. A CHF mouse model was established using aortic ligation surgery to investigate the regulation of the IL6/JAK/STAT3 pathway by QLP in CHF mice. Network pharmacology analysis and in vivo experimental data indicate that QLP alleviates myocardial injury and inflammatory response in CHF mice by modulating the IL6/JAK/STAT3 pathway, significantly improving cardiac function. This presents a promising therapeutic strategy for CHF treatment.
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BIOMEDICAL CHROMATOGRAPHY
·
2024
·
IF 1.8
Xiaomin Xu,Donghua Yu,Yu Wang,Peng Xu,Xin Jiang,Fang Lu,Shumin Liu
Resveratrol (Res) has been demonstrated to have beneficial effects on gouty nephropathy (GN). However, the mechanisms of Res on GN remain unclear. This study aimed to investigate the mechanisms of Res on GN. In this study, network pharmacology technology was used to predict the Res targets in the prevention and treatment of GN. Renal metabonomics was used to identify differential metabolites in kidney tissue of GN model rats. Finally, molecular docking technology was used to verify the binding ability of Res to key targets. Metabonomics analysis showed that 24 potentially important metabolites were involved in the prevention and treatment of GN with Res. After exposure to Res, metabolite levels normalized. The network pharmacology analysis showed that 24 key targets were involved in the prevention and treatment of GN disease. According to the metabolite–gene network diagram, we identified two core genes, PTGS1 and PTGS2, and found that both were involved in the arachidonic acid metabolism pathway. Molecular docking further verified the affinity of Res binding to PTGS1 and PTGS2. In conclusion, the mechanism of Res against GN may be the regulation of arachidonic acid metabolism through the regulation of PTGS 1 and PTGS 2.
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BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6068
·
IF 1.7
Wenbin Huang,Hongjian Zhang,Yayun Zhou,Xuechao Liu,Qilei Zhang,Xiaopeng Ma
Proteolysis targeting chimera (PROTAC) is emerging as a promising medicinal modality, which has aroused widespread interest among the field of pharmaceutical manufacturing in the recent years. ARV-471 is an orally active PROTAC estrogen receptor degrader against breast cancer, which leads to the ubiquitylation and subsequent degradation of estrogen receptors via the proteasome. In this study, we developed a highly sensitive liquid chromatography tandem mass spectrometry method (LLOQ = 0.5 ng/mL) for the measurement of ARV-471 in rat plasma. The acetonitrile precipitated sample was separated on ACQUITY BEH C 18 column using acetonitrile-0.1% formic acid as mobile phased with gradient elution. Multiple reactions monitoring in positive ESI mode was employed for the quantification of ARV-471 ( m/z 724.4 → 396.2). The assay showed good linearity over the concentration range of 0.5–1000 ng/mL with correlation coefficient > 0.996. The assay was validated according to FDA guidance, and all the validation parameters were within the predefined acceptance criteria. After validation, the assay was applied to the pharmacokinetic study of ARV-471 in rats. Additionally, the metabolites in rat plasma were identified using liquid chromatography–high resolution mass spectrometry. Four metabolites were identified and characterized. Hydrolysis, glucuronidation and deamination were the main metabolic pathways of ARV-471 in rats.
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