MOLECULES
·
2021
·Vol. 26
·期 8
·2327
·
IF 4.412
Yuanyuan Liu,Yanfang Yang,Bangyuan Wang,Renyun Wang,Jianmei Pang,Yu Jiang,Yuling Liu
Houttuynia essential oil (HEO) has excellent antiviral, anti-inflammatory, and other pharmacological effects, but the lack of effective analytical methods to quantify HEO in plasma has hindered its better clinical monitoring. Houttuynine (Hou) is one of the main active ingredients and quality control substances of HEO, so the pharmacokinetic study of HEO could be conducted by determining Hou blood concentration. Hou is active and not stable in plasma, which makes its blood concentration difficult to measure. In this work, a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for Hou determination in rat blood was established that involves Hou being derivatized with 2, 4-dinitrophenylhydrazine to form a stable compound to prevent degradation. Herein,p-Tolualdehyde-2,4-dinitrophenylphenylhydrazone was selected as an internal standard substance and the LC-MS/MS method was evaluated for selectivity, precision, accuracy, calibration limit, matrix effect, recovery, and stability. Good linearity (r2= 0.998) was reached in the range of 2–2000 ng/mL, and the lower limit of quantification of Hou was determined to be 2 ng/mL. The mean intra-assay accuracy ranged from 77.7% to 115.6%, whereas the intra-assay precision (relative standard deviation, RSD) was below 11.42%. The matrix effect value for Hou in rat plasma was greater than 75%, and for the internal standard (IS) it was 104.56% ± 3.62%. The extraction recovery of Hou were no less than 90%, and for the IS it was 96.50% ± 4.68%. Our method is sensitive and reliable and has been successfully applied to the pharmacokinetic analysis of Hou in rats given HEO via gavage and injection.Keywords:Houttuynia cordataThunb.;houttuynine;houttuynia essential oil;LC-MS/MS;pharmacokinetic study
研究领域:
药理学
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分析化学
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药剂学
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PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2019
·Vol. 411
·期 15
·3361-3372
·
IF 3.286
Zhang Yingyi,Li Liang,Wang Qi,Shen Mei,Han Weili,Yang Xuemei,Chen Lingyun,Ma Ande,Zhou Zhengzheng
Methamphetamine (METH) is one of the most highly addictive illicit drugs abused all over the world. Much evidence indicates that METH abuse leads to major toxicity, medical consequences, and even severe public health consequences. Existing studies usually focus on the pathomechanism of METH-induced toxicity; therefore, data on metabolites and elements correlating with particular toxicity remain scarce. The objective of the present study is to develop appropriate analytical procedures to identify the differential metabolic and elemental biomarkers on METH-induced hepatic injury to rats. The rats were administrated with METH (15 mg/mL/kg, two times per day) via intraperitoneal (i.p.) injections for four consecutive days. The alanine aminotransferase and aspartate aminotransferase activity levels of in the rat serum of the METH group increase significantly compared with those of the control group, suggesting obvious hepatic injury. The results are further confirmed by the histopathological microscopic observation. A total of 18 small molecular metabolites and 19 elements are selected to perform the simultaneous quantification based on the combination of liquid chromatography coupled with tandem mass spectrometry and inductively coupled plasma mass spectrometry. Sample preparation was optimized to cover all the analytes. Both methods are optimized and validated according to developed guidelines such as limits of detection, limits of quantification, linearity, precision, and recovery. All the obtained data are within the satisfactory range. The normalized data were processed according to the partial least squares discrimination analysis (PLS-DA) model. Five differential metabolic and six elemental markers are identified in rat plasma based on the variable importance in projection (VIP) (> 1) and t test results. Overall, the results obtained in this study demonstrate the developed methods are suitable for simultaneous determination of metabolic and elemental markers in the hepatic injury to rats induced by METH.
Graphical abstract
研究领域:
毒理学
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分析化学
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药理学
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病理学
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PubMed
高影响因子
Analytical Methods
·
2014
·Vol. 6
·期 21
·8675-8681
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IF 1.938
Waner Hou,Guanghui Liu,Xiuman Sun,Zhiyong Xie,Rongbiao Pi,Wei He,Manna Lin,Qiongfeng Liao
The aim of the present work was to develop and validate an LC-MS/MS method with electrospray ionization (ESI) for the quantification of lipoic acid–fasudil dimer (L–F 001), a novel multi-functional neuroprotective drug in rat plasma, using tetrahydropalmatine as an internal standard. The separation was carried out on a C18 column using a mobile phase consisting of acetonitrile and water (containing 5 mmol l−1 ammonium acetate adjusted to pH 5.0 with formic acid). The detection was performed by multiple reactions monitoring (MRM) mode via ESI source operating in the positive ionization mode. An linear calibration curve was obtained over the concentration range of 1.0–1000.0 ng ml−1 for lipoic acid–fasudil dimer (L–F 001). Accuracy, precision and extraction recovery of the analyte was satisfactory. The validated method was successfully applied to monitor the pharmacokinetic profile of the lipoic acid–fasudil dimer (L–F 001) after oral administration to rats.
研究领域:
药物分析
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神经科学
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药理学
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高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2018
·Vol. 410
·期 7
·2011-2018
·
IF 3.307
Yu Lingling,Wen Chao,Li Xing,Fang Shiqi,Yang Lichuan,Wang Tony,Hu Kaifeng
Quantification of endogenous and exogenous plasma glucose can help more comprehensively evaluate the glucose metabolic status. A ratio-based approach using isotope dilution liquid chromatography tandem mass spectrometry (ID LC-MS/MS) with indirect multiple reaction monitoring (MRM) of the derivative tag was developed to simultaneously quantify endo-/exogenous plasma glucose. Using diluted D-[ 13 C 6 ] glucose as tracer of exogenous glucose, 12 C 6 / 13 C 6 glucoses were first derivatized and then data were acquired in MRM mode. The metabolism of exogenous glucose can be tracked and the concentration ratio of endo/exo-genous glucose can be measured by calculating the endo-/exo-genous glucose concentrations from peak area ratio of specific daughter ions. Joint application of selective derivatization and MRM analysis not only improves the sensitivity but also minimizes the interference from the background of plasma, which warrants the accuracy and reproducibility. Good agreement between the theoretical and calculated concentration ratios was obtained with a linear correlation coefficient ( R ) of 0.9969 in the range of D-glucose from 0.5 to 20.0 mM, which covers the healthy and diabetic physiological scenarios. Satisfactory reproducibility was obtained by evaluation of the intra- and inter-day precisions with relative standard deviations (RSDs) less than 5.16%, and relative recoveries of 85.96 to 95.92% were obtained at low, medium, and high concentration, respectively. The method was successfully applied to simultaneous determination of the endo-/exogenous glucose concentration in plasma of non-diabetic and type II diabetic cynomolgus monkeys.
Graphical Abstract The scheme of the proposed ratio-based approach using isotope dilution LC-MS/MS with indirect MRM of the derivative tag for simultaneous quantification of endogenous and exogenous plasma glucose.
研究领域:
分析化学
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代谢组学
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生物医学科学
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PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2022
·
IF 3.318
Yutao Lou,Hui Qin,Qing Hu,Yitao Chai,Hongying Zhou,Mengting Chen,Qiyue Wang,Ping Huang,Jinping Gu,Yiwen Zhang
The objective of this study was to develop and validate a simple, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of three tyrosine kinase inhibitors (ceritinib, osimertinib, and crizotinib) in human plasma using a single-step protein precipitation extraction. Chromatographic separation was achieved using a Waters X Bridge C18 (2.1 mm × 100 mm, 3.5 µm) and gradient elution with 0.2 % formic acid in water and acetonitrile. The total run time was 4.0 min, and the injection volume was 5 μL. The analytes were detected in the multiple reaction monitoring mode using electrospray ionization with positive ion mode. The m / z transitions of ceritinib, osimertinib, crizotinib and nilotinib were 558.0 → 433.2, 500.0 → 72.1, 450.0 → 259.3, and 530.0 → 289.1, respectively. The method was linear in the range of 2–500 ng/mL with lower limit of quantification of 2 ng/mL. Based on the guidelines on bioanalytical methods by the FDA, the validation studies demonstrated that the three analytes were both precise and accurate at four concentration levels, and the coefficient of variation was < 10.59 % and accuracy was > 88.26 %. We present a simple, rapid, and sensitive method for the simultaneous quantification of ceritinib, osimertinib, and crizotinib in human plasma by LC-MS/MS, which could be used in routine therapeutic drug monitoring.
研究领域:
药理学
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分析化学
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临床医学
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PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 22
·7634
·
IF 4.6
Hongbo Yang,Jin Li,Jianfei Mao,Chan Xu,Jieyu Song,Feng Xie
Ochratoxins, a common class of mycotoxin in capsicum, and techniques and methods for the determination of mycotoxins in spices have been increasingly developed in recent years. An innovative and eco-friendly method of dispersive liquid–liquid microextraction (DLLME) was demonstrated in this study, based on a synthesized deep eutectic solvent (DES) combined with LC-MS/MS, for the quantification and analysis of two ochratoxins in capsicum. The DES-DLLME method parameters entail selecting the DES type (thymol:decanoic acid, molar ratio 1:1) and DES volume (100 μL). The volume of water (3 mL) and salt concentration (0 g) undergo optimization following a step-by-step approach to achieve optimal target substance extraction efficiency. The matrix effect associated with the direct detection of the target substance in capsicum was significantly reduced in this study by the addition of isotopic internal standards corresponding to the target substance. This facilitated optimal conditions wherein quantitative analysis using LC-MS/MS revealed a linear range of 0.50–250.00 µg/mL, with all two curves calibrated with internal standards showing correlation coefficients (r2) greater than 0.9995. The method’s limits of detection (LODs) and limits of quantification (LOQs) fell in the ranges of 0.14–0.45 μg/kg and 0.45–1.45 μg/kg, respectively. The method’s spiked recoveries ranged from 81.97 to 105.17%, indicating its sensitivity and accuracy. The environmental friendliness of the technique was assessed using two green assessment tools, AGREE and complexGAPI, and the results showed that the technique was more in line with the concept of sustainable development compared to other techniques for detecting ochratoxins in capsicum. Overall, this study provides a new approach for the determination of mycotoxins in a complex food matrix such as capsicum and other spices using DES and also contributes to the application of green analytical chemistry methods in the food industry.Keywords:deep eutectic solvent;dispersive liquid–liquid microextraction;ochratoxins;capsicum;green analytical chemistry
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高影响因子
MOLECULES
·
2023
·Vol. 28
·期 10
·4158
·
IF 4.6
Yichen Wang,Renjin Zheng,Pingping Wu,Youjia Wu,Lingyi Huang,Liying Huang
Tetrodotoxin (TTX) inhibits neurotransmission in animals, and there is no specific antidote. In clinical practice in China,Althaea rosea(A. roseaflower) extract has been used to treat TTX poisoning. In this work, the efficacy of the ethyl acetate fraction extract ofA. roseaflower in treating TTX poisoning in rats was investigated. A high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed to determine nine neurotransmitters in rat brain tissue, including γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT), noradrenaline (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA), epinephrine (E), and tyramine (Tyn). The detoxifying effect ofA. roseaflower was verified by comparing the changes in neurotransmitters’ content in brain tissue before and after poisoning in rats. The assay was performed in multiple reaction monitoring mode. The quantification method was performed by plotting an internal-standard working curve with good linearity (R2> 0.9941) and sensitivity. Analyte recoveries were 94.04–107.53% (RSD < 4.21%). Results indicated that the levels of 5-HT, DA, E, and NE in the brains of TTX-intoxicated rats decreased, whereas the levels of GABA, Tyn, and 5-HIAA showed an opposite trend, and HVA and DOPAC were not detected. The levels of all seven neurotransmitters returned to normal after the gavage administration of ethyl acetate extract ofA. roseaflower to prove that the ethyl acetate extract ofA. roseaflower had a therapeutic effect on TTX poisoning. The work provided new ideas for studies on TTX detoxification.Keywords:tetrodotoxin;LC-MS/MS;Althaea roseaflower;neurotransmitters;detoxification
研究领域:
药理学
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毒理学
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分析化学
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神经科学
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PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2023
·
IF 3
Guorong Ma,Pengzheng Luo,Ruiqiang Xu,Rui Ma,Lei Qiu,Chenran Xu,Rang Yang,Yating Li,Zhihao Zhao,Ling Huang,Yanhui Yang,Pei Wang
M. tuberculosis is the most successful intracellular pathogen and remains a major threat to human health. It is crucial to investigate the profile of cytoplasmic proteins from M. tuberculosis for pathogenesis, clinical markers, and protein vaccine development. In this study, six biomimetic affinity chromatography (BiAC) resins with high differences were selected for M. tuberculosis- cytoplasmic protein fractionation. All fractions were identified using liquid chromatography-mass spectrometry (LC-MS/MS) analysis. A total of 1246 M. tuberculosis proteins were detected (p < 0.05), among which 1092 M. tuberculosis proteins were identified in BiAC fractionations and 714 M. tuberculosis proteins in un-fractionations (Table S1.3.1). The majority of 66.8% (831/1246) identifications were distributed in the range of Mw 7.0–70.0 kDa, pI 3.5–8.0, and Gravy values <0.3. Furthermore, 560 M. tuberculosis proteins were detected in both the BiAC fractionations and un-fractionations. Compared with the un-fractionations, the average number of prot_matches, prot_cover, prot_sequence, and emPAI values of these 560 proteins in the BiAC fractionations were increased by 3.791, 1.420, 1.307, and 1.788 times, respectively. Overall, compared with un-fractionations, the confidence and profile of M. tuberculosis cytoplasmic proteins were improved by BiAC fractionations coupled with LC-MS/MS analysis. The strategy of BiAC fractionation can be used as an effective method for pre-separating protein mixtures in proteomic studies.
研究领域:
微生物学
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蛋白质组学
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生物信息学
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传染病学
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DOI
PubMed
高影响因子
Analytical Methods
·
2025
·
IF 2.6
Jieting Zhang,Shuo Diao,Zhen Huang,Mengyuan Wu,Xintong Wang,Yiran Zhao,Mingming Yu,Xianzhen Wang,Jingchun Yao,Guimin Zhang,Sherwin K. B. Sy,Zhihua Lv,Hai Yang
Guided by the principles of Analytical Quality by Design (AQbD), a highly selective and sensitive LC-MS/MS method was established for the simultaneous quantification of 15 compounds in Shouhui Tongbian capsules, enabling their effective quality control. The separation was carried out on a BEH C18 column (1.7 μm, 2.1 × 100 mm) with a mobile phase comprising 0.1% formic acid in 3 mM ammonium acetate aqueous solution and methanol (60 : 40, v/v) at a flow rate of 0.30 mL min−1. The method exhibited good linearity within a certain concentration range (R2 > 0.9906) depending on the compound; the precision ranged from 0.6% to 14.7% and accuracy was within 11.2%. Among the 15 detected compounds, aloin had the highest content in the Shouhui Tongbian capsules, reaching 227.3780 mg g−1, followed by betaine and L-hydroxyproline, with concentrations of 1.3204 mg g−1 and 1.2929 mg g−1, respectively. This method simultaneously detected the content of 15 compounds in five batches of Shouhui Tongbian capsules.
研究领域:
分析化学
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药物分析
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质量控制
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色谱-质谱分析
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中医药学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2017
·
IF 3.255
Katerina Grigori,Yannis L. Loukas,Anđelija Malenović,Vicky Samara,Anastasia Kalaskani,Efi Dimovasili,Magda Kalovidouri,Yannis Dotsikas
A sensitive Liquid Chromatography tandem mass spectrometry (LC–MS/MS) method was developed and validated for the quantitative analysis of three potential genotoxic impurities (318BP, M9, S5) in meropenem Active Pharmaceutical Ingredient (API). Due to the requirement for LOD values in ppb range, a high concentration of meropenem API (30 mg/mL) had to be injected. Therefore, efficient determination of meropenem from its impurities became a critical aim of this study, in order to divert meropenem to waste, via a switching valve. After the selection of the important factors affecting analytes’ elution, a Box-Behnken design was utilized to set the plan of experiments conducted with UV detector. As responses, the separation factor s between the last eluting impurity and meropenem, as well as meropenem retention factor k were used. Grid point search methodology was implemented aiming to obtain the optimal conditions that simultaneously comply to the conflicted criteria. Optimal mobile phase consisted of ACN, methanol and 0.09% HCOOH at a ratio 71/3.5/15.5 v/v. All impurities and internal standard omeprazole were eluted before 7.5 min and at 8.0 min the eluents were directed to waste. The protocol was transferred to LC–MS/MS and validated according to ICH guidelines.
研究领域:
分析化学
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药物分析
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药学
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PubMed
高影响因子
TALANTA
·
2026
·
IF 6.7
Feng Chen,Ziwei Deng,Yueping Jiang,Yayun Tan,Xiaoxia Yang,Huanhuan Li,Wendan Zhang,Xiangjin Shu,Aimin Wang,Chengfeng Qiu
Therapeutic drug monitoring (TDM) is essential for optimizing antimicrobial therapy and curbing resistance, yet conventional venipuncture limits its widespread application due to invasiveness and operational complexity. This study aimed to establish a rapid LC-MS/MS method for simultaneous quantification of 12 antimicrobial agents and to evaluate the feasibility of using fingertip capillary serum as an alternative to venous serum for TDM. A liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous quantification of vancomycin, linezolid, voriconazole, sulfamethoxazole, trimethoprim, piperacillin, cefoperazone, ceftazidime, ceftobiprole, meropenem, imipenem, and cilastatin in human serum. The method was applied to analyze 379 paired clinical samples (fingertip serum versus venous serum), and agreement between the two sampling approaches was assessed using Deming regression and Bland Altman analysis. The method required only 10 μL of serum and a total run time of 4 min. Deming regression slopes ranged from 0.910 to 1.017. Bland Altman analysis showed that 100.0% of the data points fell within ±20.0% limits of agreement for all antibiotics except vancomycin (96.7%) and cilastatin (97.5%). This study provides large scale clinical evidence demonstrating high concordance between fingertip serum and venous serum concentrations for 12 antimicrobial agents. By directly obtaining serum, this approach fundamentally avoids the hematocrit effect and matrix conversion issues inherent in whole blood microsampling, offering a minimally invasive TDM strategy fully aligned with the gold standard matrix. This strategy is particularly suitable for special populations such as children, the elderly, and critically ill patients.
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高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2026
·
IF 4
Jinlin He,Luying Shen,Dunming Xu,Ting Sun,Yan Chen,Jinsheng Hu,Yan Ji,Lijuan Yan
First demonstration of C18-column HILIC-like separation for aminoglycosides. • Hydrophilic retention via water layer & vicinal silanols on base-deactivated silica. • Tandem WCX-C18 SPE protocol developed for effective matrix cleanup. • Robust, MS-compatible, practical monitoring of aminoglycoside residues in foods. An LC–MS/MS method was developed for the simultaneous determination of 16 aminoglycosides (AGs) in pork, chicken, milk, and eggs using a conventional Hypersil base-deactivated silica (BDS) C 18 column operated under HILIC-like conditions. Unlike typical C 18 -based methods that rely on ion-pairing reagents in the LC mobile phase, separation was achieved with an ion-pair-free mobile phase consisting only of 0.1% formic acid and acetonitrile under gradient elution. Column comparison, aqueous-fraction experiments, and SRM 870 probe testing indicated a mixed retention mechanism involving hydrophilic partitioning into a water-enriched interfacial layer and reversible interactions with accessible residual silanol sites. Because the method prioritizes MS compatibility and reproducible multi-residue quantification, compound-specific MRM transitions and matrix-matched calibration were used to ensure selectivity and quantitative reliability. The method showed good linearity (R² > 0.99), satisfactory accuracy (71.2–99.8%) with reported standard deviations, acceptable precision (CV ≤ 11.3%), and low detection limits (LODs 3–15 μg/kg; LOQs 10–50 μg/kg). Overall, this work demonstrates that a conventional C 18 column can exhibit pronounced hydrophilic selectivity under high-organic conditions, offering a practical, MS-friendly alternative for aminoglycoside residue analysis and informing future stationary-phase development for hydrophilic separations.
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高影响因子
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