Analytical Methods
·
2015
·Vol. 7
·期 5
·2155-2161
·
IF 1.821
Hai-Long Li,Zhen-Miao Qin,Hong-Die Cai,Yin-Feng Tan,Xiao-Po Zhang,Yu-Chao Luo,Bei Li,Feng Chen,Jun-Qing Zhang
The evaluation of efficacy and safety should be paralleled with the assessment of comprehensive pharmacokinetic (PK) properties for a drug candidate, and a robust bioanalytical method is a prerequisite for obtaining PK information. α-Hederin is reported to have various in vitro and in vivo activities; however, very little is known about its PK and metabolic characteristics. In this study, we have developed an efficient LC-ESI(−)-MS/MS assay for α-hederin and its sapogenin hederagenin in rat plasma. Sample cleanup involved methanol precipitation for identification analysis and liquid–liquid extraction with ethyl acetate for quantification assay. LC analysis was performed under reversed-phase conditions in the modified “pulse gradient elution” mode. Analyte identification and quantification were conducted using multiple reaction monitoring (MRM) mode with euscaphic acid as the internal standard. Under these conditions, deglycosylated metabolites and their sulfate conjugates were detected; however, hederagenin was not detected in rat plasma samples after both oral and intravenous treatments. The mean plasma clearance (CL), volume of distribution (VSS) and elimination half-life (t1/2) of α-hederin were 0.24 L h−1 kg−1, 0.25 L kg−1 and 2.67 h, respectively. The oral bioavailability (F) of α-hederin in rats was about 0.14%, which might result from the poor intestinal absorption and/or extensive biliary excretion. It is hoped that this validated method will be useful for future PK studies of α-hederin.
研究领域:
药物分析
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药理学
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代谢组学
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DOI
高影响因子
CLINICA CHIMICA ACTA
·
2023
·
IF 5
Jing Li,Xin Zhou,Morotomi Takashi,Kenichiro Todoroki,Toshimasa Toyo'oka,Qing Shi,Toufeng Jin,Jun Zhe Min
Background Recent research has been reported that N -acetyl-leucine content is significantly reduced in the saliva of diabetic patients, but no reports of detection in human nails have been found. This study aims to develop a novel method for the chiral separation of N -acetyl-DL-leucine (Ac-DL-Leu) in human fingernails to investigate the differences between healthy volunteers (HVs), prediabetes (PDs) and diabetic patients (DPs), and to verify its effectiveness in early warning of diabetes. Method Chiral resolution was performed using DBD-Apy pre-column derivatization on a C18 column (2.1 × 150 mm, 1.9 μm) at 40 °C, and detected by UPLC-ESI-MS/MS. Results The resolution and the limit of detection (LOD) of Ac-DL-Leu were 1.75 and 1.50 fmol, respectively. The linear range of Ac-DL-Leu was 10–2000 fmol and the determination coefficient (R 2 ) was above 0.9997. The recovery of Ac-DL-Leu in human nails was 96.92–105.69 %. The contents of Ac-D-Leu and Ac-L-Leu were analyzed in 18 HVs, 13 PDs and 16 DPs fingernails. The results showed that their contents were significantly lower in DPs than in PDs and HVs ( p < 0.0001). Conclusions A method for evaluating the effectiveness of Ac-DL-Leu enantiomers in human fingernails as a biomarker for diabetes was firstly developed.
研究领域:
分析化学
·
医学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Gaiwen Yu,Caimeng Zhang,Xingfei Li,Xiangzhen Kong,Yeming Chen,Yufei Hua
While soy yogurts offer health benefits, their wide market acceptance is limited by the less desirable flavor. This study investigated the generation of yogurt flavor volatiles and the metabolic pathways in the soymilk lactic acid bacteria (LAB) fermentation system, using dairy milk as a reference, through comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS) and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS)-based flavoromics and metabolomics. The results revealed that soy yogurts exhibited higher total volatile concentrations, but dairy yogurts demonstrated higher odor activity values (OAVs). Ten key metabolic pathways in soy-based fermentation, but 9 pathways in dairy-based system were identified. The pyruvate metabolism module served as a key node for the generation of yogurt flavor compounds in both systems; amino acid metabolic pathways were more active in soy than in dairy, while different carbohydrate metabolic pathways existed in soy-based and dairy-based systems. Expression levels of key enzymes for yogurt flavor formation were affected synergistically, antagonistically, or independently by the soy and dairy milk components. This work provides experimental evidence to solidify the theoretical framework of soymilk LAB fermentation.
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高影响因子
Analytical Methods
·
2014
·Vol. 6
·期 21
·8713-8721
·
IF 1.938
Feng Chen,Hai-Long Li,Yin-Feng Tan,Wei-Yong Lai,Zhen-Miao Qin,Hong-Die Cai,Yong-Hui Li,Jun-Qing Zhang,Xiao-Po Zhang
Euscaphic acid, a triterpene acid, exists ubiquitously in medicinal plants and demonstrates various pharmacological activities. This active compound is often used as a marker compound for quality control. Hitherto, the pharmacokinetic (PK) information is relatively scarce; therefore, it remains open to question whether the euscaphic acid reaches the target sites in the body at concentrations high enough for the claimed biological effects. A robust analytical method is prerequisite for obtaining enough PK information of euscaphic acid, which is useful for interpreting its pharmacological effects. In this study, we developed and validated a rapid liquid chromatographic tandem mass spectrometric (LC-MS/MS) method for the measurement of euscaphic acid in rat plasma. The rat plasma samples were precipitated with acetonitrile and the resulting supernatants were separated by a 4 min pulse gradient method on a Synergi Fusion-RP C18 column (4 μm, 2.0 mm i.d. × 50 mm). Ursolic acid was used as an internal standard for quantification of euscaphic acid. Deprotonated euscaphic acid and its internal standard were generated in negative electrospray ionization (ESI) mode and their precursor-to-product ion pairs (m/z 487.4→469.3 and 455.5→455.4, respectively) were used for measurement. Notably, the commonly used concentration of formic acid (HCOOH; 1‰ and 5‰, v/v) in the mobile phase seriously suppressed the signal intensity, but this mobile phase additive at a much lower concentration level (0.1‰ and 0.2‰) could overcome the matrix effects and therefore increase the sensitivity of MS detection of euscaphic acid. The newly developed bioanalytical assay possessed favorable accuracy and precision with a lower limit of quantification of 2.0 ng mL−1 and was successfully applied to PK studies in rats. The experimental strategies presented herein may be helpful for measurement of other triterpene acids in biological matrices.
研究领域:
分析化学
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药理学
·
生物医学
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DOI
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2019
·Vol. 34
·期 1
·e4703
·
IF 1.748
Shuangshuang Sun,Dongfang Cheng,Shumeng Kong,Xiangping Li,Tongfang Li,Qinglong Yu,Lin Wang
Ibrutinib has an excellent effect in the treatment of mantle cell lymphoma so it has attracted much attention. A novel ibrutinib nanocrystalline was exploited in our study to improve the bioavailability. A fast and reliable UPLC–MS/MS method was established for the accurate quantification of ibrutinib in rat plasma. The chromatographic separation was achieved by an Agilent zorbax SB-C 18 rapid solution HD column (2.1 × 50 mm, 1.8 μm). The mobile phase consisted of deionized water (containing 10 m m ammonium acetate and 0.1% formic acid) and pure acetonitrile. Isocratic elution (water–acetonitrile 10:90, v/v) was adopted and the flow rate was 0.4 mL/min. Column temperature was set to 40°C. Vilazodone was used as the internal standard in this analytical method. Multiple reaction monitoring mode with positive electrospray ionization was selected to detect ibrutinib and vilazodone. Acetonitrile was used to precipitate protein to extract plasma samples. There was no endogenous interference for both ibrutinib and vilazodone and the linear range of this method was 1–2000 ng/mL. The recoveries were 98.4, 97.4 and 102.7% at low, medium and high concentrations. Accordingly, the matrix effect was 96.6, 111.1 and 99.6%. The pharmacokinetic difference between ibrutinib crude and a novel ibrutinib nanocrystalline in rats was investigated by this validated method successfully. The peak concentration and area under the concentration–time curve showed significant differences in gender and the bioavailability was improved after oral administration of ibrutinib nanocrystalline.
研究领域:
药物分析
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药理学
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生物医学工程
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DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2017
·
IF 3.255
Bing Chen,Xuewen Wang,Yulian Zou,Weiying Chen,Gang Wang,Wensong Yao,Peiying Shi,Shaoguang Li,Shilan Lin,Xinhua Lin,Hong Yao
Selaginella doederleinii Hieron is a widely used as folk Chinese medicine for treatment of different cancers. Our previous investigations have confirmed that the total biflavonoids in ethyl acetate extract from S. doederleinii (SDEA) have favorable anticancer potentials. However, the in vivo process of its bioactive ingredients remains unknown. In this paper, a sensitive and reliable method was developed for simultaneous quantification of main five biflavonoids, including amentoflavone , robustaflavone, 2″,3″-dihydro-3′,3″-biapigenin, 3′,3″-binaringenin and delicaflavone in the ethyl acetate extract of S. doederleinii (SDEA extract) in rat plasma by high-performance liquid chromatography with electrospray ionization-mass spectrometry (HPLC-ESI–MS/MS). Chromatographic separation was performed using an Ultimate ® XB-C18 (100 × 2.1 mm, 3.5 μm) with gradient elution of water (0.5% acetic acid) and acetonitrile at 0.2 mL/min. All analytes with internal standard (chrysin) were detected using selective reaction monitoring (SRM) in negative ionization mode. The method showed a good linearity over a wide concentration range (r 2 > 0.99). The limits of quantification for the biflavonoids were less than 10 ng/mL. The developed method was applied to the comparatively pharmacokinetic study of the five biflavonoids after oral or intravenous administration of SDEA extract in rats. In addition, in silico assessments of permeability and solubility of these biflavonoids were also performed to understand their poor bioavailability. It is the first time to report the in vivo process profiles of the biflavonoids of SDEA extract in rats.
研究领域:
药理学
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分析化学
·
中药学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2020
·
IF 6.306
Jiaxin Wang,Xuening Lu,Jiaen Zhang,Zeheng Xiao
Lipids such as phosphatidylcholine (PC), 3- sn -phosphatidylethanolamine (PE), sphingomyelin (SM) and L-α-lysophosphatidylcholine (LPC) are the major components of biological membranes and play important roles in physiological functions. Here, PC, PE, SM, and LPC were extracted from golden apple snails (GAS, Pomacea canaliculata ) and GAS flesh (GASF) using an ethanol/hexane sequential scheme and quantified simultaneously using ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) to evaluate whether the GAS could be the source of the four lipids. Our results suggest that ethanol extracts contained the most crude lipids, and the yield of dry (evaporated) lipids were 3.45 g per 100 g fresh GASF and 1.82 g per 100 g of fresh GAS. Quantification of the lipids using UHPLC-ESI-MS/MS suggested that GAS contained PE, PC, SM and LPC, with SM being the most abundant lipid (after purification: 1.71 and 1.42 mg g −1 dry weight from 100 g of GASF and GAS, respectively). The method we used is cost-effective, and the recovery rates of ethanol and hexane ranged from 80−91% and 87−91% respectively. Overall, GAS and GASF are potential raw materials for lipids such as SM and PC extraction using the ethanol/hexane method. Comparatively, lipids extraction from the GAS is more effective and timesaving. Our finding would provide a way to utilize GAS and potentially control its invasion.
研究领域:
生物化学
·
分析化学
·
入侵生物学
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Mengqing Yang,Jianhai Yang,Rong Liu,Liping Chen,Danyang Chen,Yu He,Yang Li,Huaying Wang,Keqi Tang,Zhengyan Hu,Zhenbin Zhang
Capillary coating plays a crucial role in the separation efficiency and reproducibility of capillary zone electrophoresis (CZE). In this study, a linear poly(N-(2-hydroxypropyl)methacrylamide) (LP(HPMA))-coated capillary was prepared by using the surface-confined aqueous reversible addition–fragmentation chain transfer polymerization method. The LP(HPMA)-coated capillary exhibits better biocompatibility and stability compared with the linear poly(acrylamide) (LPA)-coated capillary. Through systematic evaluation, the optimal conditions for fabricating LP(HPMA)-coated capillaries were determined as follows: 1 M HPMA, 2.7 × 10–3 M 4,4′-azobis(4-cyanovaleric acid), and a reaction time of 4 h. LP(HPMA)-coated capillaries prepared under these conditions exhibited the lowest electro-osmotic flow values of 3.7 × 10–6 and demonstrated exceptional performance when applied to the analysis of a HeLa cell digest. Following a 20-day treatment with 2 M NH4OAc (pH 7), the number of peptides identified using the LP(HPMA)-coated capillary decreased by 18.1% compared to the untreated LP(HPMA)-coated capillary; in contrast, the peptide numbers for the LPA-coated capillary decreased by 26.7% relative to its untreated counterpart. These results indicate that the LP(HPMA)-coated capillary exhibits superior pH stability compared to the LPA-coated capillary within the physiological pH range. The LP(HPMA)-coated capillary was employed in the clinical proteomics analysis of non-small cell lung cancer tissues and their corresponding paracancerous tissues via CZE-ESI-MS/MS. The differentially expressed proteins in each sample pair demonstrated minimal overlap, highlighting the heterogeneity of tumor tissues among different patients. Principal component analysis of the data could segregate the samples into a tumor tissue cluster and a paracancerous tissue cluster. Moreover, within each cluster, samples from different patients further separated into subclusters. This discovery validates that CZE-MS can not only distinguish between lung cancer tumor tissue and paracancerous tissue but also detect the heterogeneity among diverse patients, even with as little as 100 ng of sample. The obtained results were subsequently compared with those from nanoRPLC-MS using 1 μg of sample. Notably, the enrichment results within the three gene ontology categories for both methods showed a high level of consistency, corroborating the effectiveness of the CZE-MS method using an LP(HPMA)-coated capillary in identifying differentially expressed proteins from mass-limited clinical samples.
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PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2021
·
IF 3.232
Xin Li,Huan Tong,Bing Xu,Yang Deng,Yuan Li,Junchen Huang,Yong Mao,Mengqin Liu,Ping Zhang,Siwei Guo
Budesonide is one of the intranasal corticosteroids, referred as first-line therapy for allergic rhinitis. Its determination is a challenging task due to its extremely low plasma levels, which limits the progress in the investigation of pharmacokinetics and quality control of preparations. In this study, a sensitive and high-throughput method to determine budesonide in human plasma using budesonide-d8 as the internal standard was developed and validated. A small volume of plasma sample (0.2 mL) was diluted with 0.2 mL water, followed by a solid-phase extraction using Cleanert PEP-2 products. Extracted samples were analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Chromatographic separation of analytes was performed on an InertSustain AQ-C18 HP column (3 µm, 2.1 × 50 mm) under the reversed-phase condition with gradient elution. With the assay, linear calibration curves were obtained over the concentration range of 10–1200 pg/mL for budesonide, with considerable extraction recoveries (84.7–89.4%), and negligible matrix effects (<4.1). Moreover, the newly developed method was successfully applied to the evaluation of pharmacokinetics of two budesonide intranasal formulations with and without charcoal block in healthy volunteers.
研究领域:
药理学
·
分析化学
·
临床医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2021
·
IF 4.759
Yuhao Han,Panpan Chen,Zhichao Li,Xiao Wang,Chenglong Sun
Ultraviolet (UV) light-catalyzed Paternò-Büchi (PB) reaction has been developed as an efficient lipid C=C double bond (DB) derivatization strategy, which can accurately assign the position of C=C bond in unsaturated lipids when coupled with tandem mass spectrometry (MS/MS). Inspired by this, here we proposed a novel visible-light induced [2+2] cycloaddition reaction combined with ESI-MS/MS and MALDI-MS/MS to identify lipid C=C position isomers. Benz[g]isoquinoline-5,10-dione (BIQD) and 6,9-difluorobenzo[g]isoquinoline-5,10-dione (DF-BIQD) were developed as a new type of [2+2] cycloaddition reagent, which can not only react with C=C bond under 254 nm UV light irradiation, but also quickly combine with lipid C=C bond under the irradiation of 405 nm visible-light and > 400 nm compact fluorescent lamp visible-light. High cycloaddition reaction conversion efficiency can be achieved by irradiating under compact fluorescent lamp light for 2 min. Moreover, we discovered that 437 nm, 489 nm, 545 nm, 581 nm, and 613 nm monochromatic light appearing in compact fluorescent lamp can individually induce the [2 + 2] cycloaddition reaction between DF-BIQD and unsaturated lipids. Using this method, we found that the expressions of lipid DB-positional isomers in rat heart, brain, lung, spleen, thymus, kidney, liver and plasma vary greatly. The relative content of FA-18:1 (Δ9) in rat heart is only 1.49 times that of FA-18:1 (Δ11), while the relative content of FA-18:1 (Δ9) in rat plasma is 5.20 times that of FA-18:1 (Δ11). The above results offer new insight into the development of photocatalytic reagent for visible-light induced [2+2] cycloaddition and structural lipidomic studies.
研究领域:
化学
·
生物化学
·
分析化学
·
脂质组学
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2019
·
IF 3.407
Wen-Jing Wu,Wei-Feng Tang,Ming-Hui Xiang,Jianshe Yan,Xiumei Cao,Chang-Hui Zhou,Yan Chang,Jing Xi,Yi-Yi Cao,Yang Luan,Xin-Yu Zhang
1-Chloro-2-hydroxy-3-butene (CHB) is a possible metabolite of 1,3-butadiene, a carcinogenic air pollutant . To demonstrate its formation in vivo, it is desirable to develop a practical biomarker and the corresponding analysis method. CHB can undergo alcohol dehydrogenase- and cytochromes P450 enzymes (P450)-mediated oxidation to yield 1-chloro-3-buten-2-one (CBO), which readily forms glutathione conjugates. We hypothesized that CBO-derived mercapturic acids , which are the expected biotransformed products of CBO-glutathione conjugates, could be used as CHB biomarkers. Thus, in the present study, we investigated the in vivo biotransformation of CHB into CBO-derived mercapturic acids. Because the reaction of CBO with N -acetyl- l -cysteine yields two products, 1,4- bis ( N -acetyl- S -cysteinyl)-2-butanone (NC1) and 1-chloro-4-( N -acetyl- S -cysteinyl)-2-butanone (NC2), we first developed an isotope dilution LC/ESI − -MS-MS method to quantitate urinary NC1 and NC2, and then determined their concentrations in urine of C57BL/6 mice and Sprague-Dawley rats administered CHB. Since no NC2 was detected in samples, the LC/ESI − -MS-MS method was optimized specifically for NC1. NC1 was enriched through solid phase extraction with the recovery being 75–82%. The limits of detection and quantitation were 6.8 and 34 fmol/0.1 mL for mouse urine, and 4.5 and 7.1 fmol/0.1 mL for rat urine, respectively. In urine of animals before CHB administration, no NC1 was detected; in mice administered CHB at 10 and 30 mg/kg, and rats at 5 and 15 mg/kg, NC1 was detected and its concentrations in urine from animals given higher doses were 3–6 fold higher than those given lower doses. Moreover, the NC1 concentrations in urine during 0–8 h were 4–6 fold and 10–11 fold higher than those during 8–24 h for mice and rats, respectively. The results demonstrated that CHB could be in vivo biotransformed into NC1, which could be used as a practical CHB biomarker.
研究领域:
毒理学
·
分析化学
·
环境科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shuangyu Shao,Xiali Si,Yingtao Zhang,Jun Li,Pengfei Tu,Qingying Zhang
Quality analysis of edible mushrooms based on polysaccharides is generally difficult due to their complicated structures and hard separation. Here, multiple fingerprint analysis of polysaccharides based on chromatographic and spectrometric techniques were developed, and then applied in comparative analysis of Auricularia heimuer (AH), Auricularia cornea (AC), Auricularia cornea ʻYu Muerʼ (ACY) and Tremella fuciformis (TF). Firstly, polysaccharides were obtained with the molecular weights between 1.783 × 10 6 and 6.774 × 10 6 Da. Then, complete hydrolysis by TFA and enzyme digestion by cellulase were employed and subsequently analyzed by HPLC-UV, GC–MS, HILIC-HPLC-ELSD and HILIC-HPLC-ESI − -HCD-MS/MS, and ATR-FT-IR were used to characterize the functional groups of intact polysaccharides. By chemometric analysis, differential markers of d -xyl, l -fuc, l -arb, d -glc, disaccharide and hexasaccharide were selected, and AC and ACY were proved to be same species from the viewpoint of polysaccharides firstly. Furthermore, the structures of oligomers with DPs of 2–8 and →4)- β - d -Glc p -(1→ unit with different contents were inferred by combinatory analysis of ESI − -MS/MS, glycosidic linkage, monosaccharide compositions and functional groups. In conclusion, the combinatory method of multiple fingerprint and pattern recognition is powerful not only for structural elucidation of polysaccharides, but also for quality analysis and species differentiation of edible mushrooms from the perspective of biological polysaccharides.
研究领域:
食品科学
·
分析化学
·
真菌学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）