BIOMEDICAL CHROMATOGRAPHY
·
2016
·Vol. 31
·期 4
·e3860
·
IF 1.729
Yan Du,Yin-jie Li,Xun-xiu Hu,Xu Deng,Zeng-ting Qian,Zheng Li,Meng-zhe Guo,Dao-quan Tang
As essential endogenous compounds, nucleobases and nucleosides fulfill various functions in living organisms. This study presents the development and validation of a new hydrophilic interaction liquid chromatography tandem mass spectrometry method for simultaneous quantification of 19 nucleobases and nucleosides in rat plasma. For the sample preparation, 15 kinds of protein precipitants were evaluated according to the chromatographic profile and ion response of analytes. The optimization of chromatographic separation was respectively performed using reversed-phase liquid chromatography and hydrophilic interaction liquid chromatography mode; each separation mode included two test columns with different stationary phases. The chromatographic profile and parameters such as half-width ( W 1/2 ), capacity factor ( K ′) and tailing factor ( f t ) were used to evaluate the separation efficiencies. Furthermore, the adopted composition of two mobile phase systems and the concentrations of the additives in the optimum buffer system were also investigated. The developed method was fully validated and successfully applied quantitatively to determine 19 nucleobases and nucleosides in plasma from normal and diabetic nephropathy (DN) rats. Significant differences between normal and DN rats were found in plasma levels of cytosine, xanthine, thymidine, adenosine, guanosine, inosine and 8-hydroxy-2′-deoxyguanosine. This information may provide a useful reference for the discovery of potential biomarkers of DN.
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2016
·Vol. 31
·期 7
·e3905
·
IF 1.729
Danyu Kang,Ting Geng,Yuanpei Lian,Yanjing Li,Gang Ding,Wenzhe Huang,Shiping Ma,Zhenzhong Wang,Zheng Ma,Wei Xiao
The aim of this study was to investigate the direct inhibitory effects of Re Du Ning Injection (RDN) and its active compounds on the major cytochrome P450 enzyme (CYP) isoforms (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) of human liver microsomes by ‘a cocktail method’. The activity of each CYP isform was represented as the formation rate of the specific metabolite from relevant substrate. Then a sensitive and specific ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated to simultaneously analyze the seven metabolites. RDN (0.035–2.26 mg/mL) showed a strong inhibitiory effect on CYP2C8, followed by CYP2C9, CYP2B6, CYP2C19, CYP1A2 and CYP3A4. The IC 50 value for each enzyme was 0.19, 0.66, 0.72, 1.27, 1.66 and 2.13 mg/mL, respectively. RDN competitively inhibited the activities of CYP1A2 ( K i = 1.22 mg/mL), CYP2B6 ( K i = 0.65 mg/mL) and CYP3A4 ( K i = 0.88 mg/mL); it also exhibited mixed inhibition of CYP2C8, CYP2C9 and CYP2C19 with a K i value of 0.26, 0.64 and 0.82 mg/mL, respectively. However, the activity of CYP2D6 was not significantly inhibited even by 2.26 mg/mL RDN. Moreover, the data of nine active compounds on the CYPs showed that cryptochlorogenin acid, sochlorogenic acid B and sochlorogenic acid C were the major contributors to the inhibitory effect of RDN on CYP2C8, while the inhibitory effect of RDN on CYP2C9 might be caused by sochlorogenic acid A and sochlorogenic acid C. Moreover, neochlorogenic acid might be the major contributor to the inhibitory effect on CYP2B6. All of the findings suggested that drug–drug interactions may occur and great caution should be taken when RDN is combined with drugs metabolized by these CYPs.
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BIOMEDICAL CHROMATOGRAPHY
·
2016
·Vol. 30
·期 8
·1331-1337
·
IF 1.729
Jincheng Li,Huan Liu,Jing Zhang,Yang Liu,Lidong Wu
A simple, fast and low-cost extraction method with high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) determination was developed on sulfonamide antibiotics (SAs) in fish tissue. Magnetic separation was first introduced into the rapid sample preparation procedure combined with acetonitrile extraction for the analysis of SAs. Partitioning was rapidly achieved between acetonitrile solution and solid matrix by applying an external magnetic field. Acetonitrile solution was collected and concentrated under a nitrogen stream. The residue was redissolved with 1‰ formic acid aqueous solution and defatted with n- hexane before analysis. The recoveries of SAs were in the range of 74.87–104.74%, with relative standard deviations <13%. The limits of quantification and the limits of detection for SAs ranged from 5.0 to 25.0 μg kg−1 and from 2.5 to 10.0 μg kg−1 , respectively. The presented extraction method proved to be a rapid method which only took 20 min for one sample preparation procedure. Copyright © 2016 John Wiley & Sons, Ltd.
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BIOMEDICAL CHROMATOGRAPHY
·
2016
·Vol. 31
·期 3
·e3814
·
IF 1.729
Shihui Bao,Jing Zhang,Zixia Lin,Ke Su,Jingjing Mo,Lin Hong,Shuyi Qian,Lianguo Chen,Fa Sun,Congcong Wen,Qing Wu,Lufeng Hu,Guanyang Lin,Xianqin Wang
Dextromethorphan is recognized as a substance of abuse around the world. An estimated 3.1 million people between the ages of 12 and 25 years (5.3%) misused over-the-counter cough and cold medications in 2006. In this study, we developed a serum metabolomic method by gas chromatography–mass spectrometry (GC–MS) to evaluate the effect of abuse of dextromethorphan on rats. The dextromethorphan-treated rats were given 12, 24 and 48 mg/kg (low, medium, high) of dextromethorphan by intragastric administration each day for 3 days. Partial least squares-discriminate analysis revealed that intragastric administration of dextromethorphan induced metabolic perturbations. Compared with the control (healthy) group, the levels of propanoic acid, urea, heptafluorobutanoic acid, 2-hexyldecanoic acid and butanedioic acid of the low group decreased; levels of propanoic acid and heptafluorobutanoic acid of the medium group decreased, while that of benzoic acid increased; and levels of 2-hexyldecanoic acid, glycerol and butanedioic acid of the high group increased. These biomarkers are involved in the citric acid cycle, urea cycle, glycerolipid metabolism and tricarboxylic acid cycle. The results indicate that the metabolomic method by GC–MS may be useful to elucidate abuse of dextromethorphan. According to the pathological changes in the liver at different dosages, dextromethorphan is not hepatotoxic after intragastric administration of 12, 24 and 48 mg/kg for 3 days.
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BIOMEDICAL CHROMATOGRAPHY
·
2017
·Vol. 32
·期 2
·e4094
·
IF 1.613
Guogai Zhang,Lifang Zhao,Jiancheng Zhu,Yifan Feng,Xia Wu
Alpinia officinarum is used for its anti-inflammatory activity historically in China. Diarylheptanoids isolated from A. officinarum play important biological roles in the prevention and treatment of inflammatory disorders. Seven diarylheptanoids (1–7) were isolated from A. officinarum . The cell viabilities and anti-inflammatory activities of diarylheptanoids were evaluated by MTT assay and tumor necrosis factor- α production in Kdo2-lipid A-stimulated RAW 264.7 cells in vitro . The relationships between their anti-inflammatories and structure-activities are discussed. The results indicated that compounds 1 and 3–7 had significant anti-inflammatory activities. The relationships between inflammation and phospholipids metabolism were elucidated by multivariate data analysis. Twenty-two potential biomarkers were identified in inflammatory group vs. blank group, and 11 potential biomarkers were identified for inflammatory group vs. drug-treatment groups. Ten common phospholipids were characterized. On the basis of a previous study in our laboratory, we found that phosphatidylethanolamine (18:0/18:1) might be the important glycerophospholipid biomarker in inflammation. In this study, we firstly combined anti-inflammatory activities and glycerophospholipids changes of traditional Chinese medicine. This work suggests that the anti-inflammatory activities of diarylheptanoids might be significantly related to glycerophospholipids and could provide a useful database for investigating the anti-inflammatory effects of traditional Chinese medicine.
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2017
·Vol. 32
·期 3
·e4114
·
IF 1.613
Hongli Du,Hai Zhang,Yahong Zhao,Min Liu,Anni Chen,Shiyu Liu,Dan Xue,Yanjun Liu,Guoqing Zhang
In recent years, vascular depression has become the focus of international attention. Yangxinshi Tablet (YXST) is usually used in cthe linic for the treatment of arrhythmia and heart failure, but we found that it also has antidepressive effects. The objective of the study was to identify biomarkers related to vascular depression in hippocampus and explore the antidepressive effects of YXST on the mouse model. Untargeted metabolomics based on UHPLC-Q-TOF/MS was applied to identify significantly differential biomarkers between the model group and control group. Unsupervised principal component analysis (PCA) was used to scan the tendency of groups and partial least squares-discriminant analysis (PLS-DA) to distinguish between the vascular depressive mice and the sham. PCA stores showed clear differences in metabolism between the vascular depressive mice and sham groups. The PLS-DA model exhibited 38 metabolites as the biomarkers to distinguish the vascular depressive mice and the sham. Further, YXST significantly regulated 22 metabolites to normal levels. The results suggested that YXST has a comprehensive antidepressive effect on vascular depression via regulation of multiple metabolic pathways including amino acid, the tricarboxylic acid cycle and phosphoglyceride metabolisms. These findings provide insight into the pathophysiological mechanism underlying vascular depression and the mechanism of YXST.
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2017
·Vol. 31
·期 12
·e4036
·
IF 1.613
Jing Yu,Hai Zhang,Ying Li,Sen Sun,Jie Gao,Yanqiang Zhong,Duxin Sun,Guoqing Zhang
Cationic liposomes (CLs) are novel nonviral vectors widely used for delivering drugs or genes. However, applications of CLs are largely hampered by their cytotoxicity, partly because the potential mechanism underlying the cytotoxicity of CLs remains unclear. The aim of the present study was to explore the underlying mechanism of cytotoxicity induced by CLs on HepG2 cells. Differential metabolites were identified and quantified using ultra-liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). The toxicity of CLs on HepG2 cells was evaluated by multivariate data analysis and statistics. Additionally, CCK-8 assay, heatmap, pathway and co-expression network were carried out to explore the relations between the metabolites and the pathways. The results showed a dose-dependent toxic effect of CLs on HepG2 cells, with an IC 50 value of 119.9 μg/mL. Multivariate statistical analysis identified 42 potential metabolites between CLs exposure and control groups. Pathway analysis showed significant changes in pathways involving amino acid metabolism, energy metabolism, lipid metabolism and oxidative stress in the CLs exposure group vs the control group. Metabolites related to the above-mentioned pathways included phenylalanine, methionine, creatine, oxalacetic acid, glutathione, oxidized glutathione, choline phosphate and several unsaturated fatty acids, indicating that cells were disturbed in amino acid metabolism, energy and lipid supply when CLs exposure-induced injury occurred. It is concluded that CLs may induce cytotoxicity by enhancing reactive oxygen species in vitro , affect the normal process of energy metabolism, disturb several vital signaling pathways and finally induce cell death.
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2017
·Vol. 31
·期 9
·e3956
·
IF 1.613
Yan Li,Gaotong Lin,Bingbao Chen,Jing Zhang,Lingtian Wang,Zixia Li,Yungang Cao,Congcong Wen,Xuezhi Yang,Gaozhong Cao,Xianqin Wang,Guoquan Cao
We developed a serum metabolomic method by gas chromatography–mass spectrometry (GC–MS) to evaluate the effect of alprazolam in rats. The GC–MS with HP-5MS (0.25 μm × 30 m × 0.25 mm) mass was conducted in electron impact ionization (EI) mode with electron energy of 70 eV, and full-scan mode with m / z 50–550. The rats were randomly divided to four groups, three alprazolam-treated groups and a control group. The alprazolam-treated rats were given 5, 10 or 20 mg/kg (low, medium, high) of alprazolam by intragastric administration each day for 14 days. The serum samples were corrected on the seventh and fourteenth days for metabolomic study. The blood was collected for biochemical tests. Then liver and brain were rapidly isolated and immersed for pathological study. Compared with the control group, on the seventh and fourteen days, the levels of d -glucose, 9,12-octadecadienoic acid, butanoic acid, l -proline, d -mannose and malic acid had changed, indicating that alprazolam induced energy metabolism, fatty acid metabolism and amino acid metabolism perturbations in rats. There was no significant difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea and uric acid between controls and alprazolam groups. According to the pathological results, alprazolam is not hepatotoxic. Metabolomics could distinguish different alprazolam doses in rats.
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2012
·Vol. 27
·期 4
·509-514
·
IF 1.966
Linling Lu,Dawei Qian,Jing Yang,Shu Jiang,Jianming Guo,Er-xin Shang,Jin-ao Duan
In this paper, ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and the MetaboLynx™ software combined with mass defect filtering were applied to identity the metabolites of isoquercitrin using an intestinal mixture of bacteria and 96 isolated strains from human feces. The human incubated samples collected for 72 h in the anaerobic incubator and extracted with ethyl acetate were analyzed by UPLC-Q-TOF/MS within 10 min. The parent compound and five metabolites were identified by eight isolated strains, including Bacillus sp. 17, Veillonella sp. 23 and 32 and Bacteroides sp. 40, 41, 56, 75 and 88 in vitro . The results indicate that quercetin, acetylated isoquercitrin, dehydroxylated isoquercitrin, hydroxylated quercetin and hydroxymethylated quercetin are the major metabolites of isoquercitrin. Furthermore, a possible metabolic pathway for the biotransformation of isoquercitrin was established in intestinal flora. This study will be helpful for understanding the metabolic route of isoquercitrin and the role of different intestinal bacteria in the metabolism of natural compounds. Copyright © 2012 John Wiley & Sons, Ltd.
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2015
·Vol. 29
·期 11
·1737-1743
·
IF 1.723
Xue-jia Zhai,Fen Chen,Chao-ran Zhu,Yong-ning Lu
Many amino acid neurotransmitters in urine are associated with chronic stress as well as major depressive disorders. To better understand depression, an analytical LC-MS/MS method for the simultaneous determination of 11 underivatized neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate, pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single analytical run was developed. The advantage of this method is the simple preparation in that there is no need to deconjugate the urine samples. The quantification range was 25–12,800 ng mL −1 with >85.8% recovery for all analytes. The nocturnal urine concentrations of the 11 neurotransmitters in chronic unpredictable mild stress (CUMS) model rats and control group ( n = 12) were analyzed. A series of significant changes in urinary excretion of neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate and tyramine concentrations were significantly lower in the CUMS group. In addition, the urinary concentrations of tryptophan as well as tyrosine were significantly higher in chronically stressed rats. This method allows the assessment of the neurotransmitters associated with CUMS in rat urine in a single analytical run, making it suitable for implementation as a routine technique in depression research. Copyright © 2015 John Wiley & Sons, Ltd.
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2015
·Vol. 30
·期 4
·601-605
·
IF 1.723
Zhaoli Ling,Ping Xu,Zeyu Zhong,Fan Wang,Nan Shu,Ji Zhang,Xiange Tang,Li Liu,Xiaodong Liu
A new pre-column derivative high-performance liquid chromatography (HPLC) method for determination of d -glucose with 3- O -methyl- d -glucose (3-OMG) as the internal standard was developed and validated in order to study the gluconeogenesis in HepG2 cells. Samples were derivatized with 1-phenyl-3-methy-5-pyrazolone at 70°C for 50 min. Glucose and 3-OMG were extracted by liquid–liquid extraction and separated on a YMC-Triart C 18 column, with a gradient mobile phase composed of acetonitrile and 20 m m ammonium acetate solution containing 0.09% tri-ethylamine at a flow rate of 1.0 mL/min. The eluate were detected using a UV detector at 250 nm. The assay was linear over the range 0.39–25 μ m ( R 2 = 0.9997, n = 5) and the lower limit of quantitation was 0.39 μ m (0.070 mg/mL). Intra- and inter-day precision and accuracy were <15% and within ±3%, respectively. After validation, the HPLC method was applied to investigate the gluconeogenesis in Dulbecco's modified Eagle medium (DMEM) cultured HepG2 cells. Glucose concentration was determined to be about 1–2.5 μ m in this gluconeogenesis assay. In conclusion, this method has been shown to determine small amounts of glucose in DMEM successfully, with lower limit of quantitation and better sensitivity when compared with common commercial glucose assay kits. Copyright © 2015 John Wiley & Sons, Ltd.
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2013
·Vol. 28
·期 7
·994-1002
·
IF 1.945
Ting Zhou,Ting Zhao,Qing Cheng,Shan Liu,Ling Xu,Wen Tan
A sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of R -bambuterol and its active metabolite R -terbutaline in human plasma and urine was established. The inhibition for the biotransformation of R -bambuterol in plasma was fully investigated. Plasma samples were prepared on ice and neostigmine metilsulfate added as a cholinesterase inhibitor immediately after sample collection. All samples were extracted with ethyl acetate and separated on a C 18 column under gradient elution with a mobile phase consisting of methanol and water containing 5 m m ammonium acetate at a flow rate of 0.6 mL/min. The analytes were detected by an API 4000 tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 10.00 pg/mL for each analyte in plasma. In urine samples, the LLOQs were 20.00 and 500.0 pg/mL for R -bambuterol and R -terbutaline, respectively. The intra- and inter-day precisions were <12.7 and <8.6% for plasma and urine, respectively. The analytical runtime within 6.0 min per sample made this method suitable for high-throughput determination. The validated method has been successfully applied to the human pharmacokinetic study of R -bambuterol involving 10 healthy volunteers. Copyright © 2013 John Wiley & Sons, Ltd.
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