ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2021
·Vol. 413
·期 7
·1799-1807
·
IF 4.157
Ouyang Zhonghua,Huang Jing,Ren Yi,Li Huanhuan,Ding Yao,Zhang Ke,Jiang Lei,Yu Peng
High-dose methotrexate (HDMTX) combined with leucovorin (LV) is the first-line drug therapy for many kinds of malignant tumors. However, the specific treatment plans, such as dosage and duration of administration, are usually formulated according to the clinician’s experience and therapeutic drug monitoring (TDM) of methotrexate in patients’ plasma, which are responsible for strong individual differences of drug usage. A large number of studies have shown that methotrexate targets the inside of the cell. The key cytotoxic component is the methotrexate polyglutamates (MTXPGs) in the cell. The concentration of methotrexate in plasma does not reflect the efficacy and side effects well. Based on mass spectrometry technology, we developed and validated an accurate, sensitive, and stable method to quantify the intracellular MTX (MTXPG 1 ) and its metabolites MTXPG 2–7 simultaneously. The lower limit of quantification was 0.100 ng/ml, and the run time was only 3 min. Moreover, our team has already developed two LC-MS/MS-based methods to respectively quantify methotrexate in plasma samples and two key proteins (γ-glutamyl hydrolase [GGH] and folylpolyglutamate synthetase [FPGS]) in peripheral blood mononuclear cells (PBMC). Through these highly sensitive and accurate approaches, we have gained a deep understanding of the whole pharmacokinetic process of MTX and explored the key factors affecting the accumulation process of intracellular active components (MTXPGs). Based on this research, it is possible to find a more effective way to provide an accurate reference for clinical drug use than traditional therapeutic drug monitoring (TDM).
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2018
·
IF 2.831
Hong Pan,Yi Li,Linyan Huang,Xumei Zhou,Yuanfu Lu,Fuguo Shi
Arecoline is the primary active and toxic constituent of areca nut. Arecaidine and arecoline N -oxide are two major active metabolites of arecoline. In this work, an accurate and simple high performance liquid chromatography tandem mass spectrometry method for simultaneous quantification of arecoline, arecaidine and arecoline N -oxide in rat plasma was developed and fully validated to study their pharmacokinetic behaviors in rats. After extracted from rat plasma by protein precipitation with methanol and then concentrated, the analytes were chromatographic separated on a Sepax Sapphire C 18 analytical column. The mobile phase consisted of methanol and 2 mM ammonium acetate buffer solution containing 0.2% ( v/v ) formic acid (8:92, v/v ) under isocratic elution. The analytes were detected by multiple reaction monitoring (MRM) with an electrospray ionization source in the positive ion mode. The transitions of m / z 156.2 → 53.2, m / z 142.2 → 44.2 and m / z 172.2 → 60.2 were selected for arecoline, arecaidine and arecoline N -oxide, respectively. The method was linear over the concentration range of 0.5–100 ng/mL for arecoline, 5–5000 ng/mL for arecaidine and arecoline N -oxide with no carry-over effect. The accuracies and intra- and inter-batch precisions were all within the acceptance limits. No matrix effect and potential interconversion between the analytes and other metabolites were observed in this method. The validated method was further employed to a preclinical pharmacokinetic study of arecoline, arecaidine and arecoline N -oxide after oral treatment with 20 mg/kg arecoline to rats.
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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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FOOD RESEARCH INTERNATIONAL
·
2023
·
IF 8.1
Qiannan Zhao,Jinyi Yang,Jiahui Li,Lei Zhang,Xiaohai Yan,Tianli Yue,Yahong Yuan
Phenolics of mulberry ( Morus alba L.) leaves (MLs) have potential anti-diabetic effects, but they may be chemically modified during gastrointestinal digestion so affect their biological activity. In this study, an in vitro digestion model coupled with Caco-2 monolayer and Caco-2/insulin-resistant HepG2 coculture model were used to study the transport and hypoglycemic effects of phenolics in raw MLs (U-MLs) and solid-fermented MLs (F-MLs). The results of LC-MS/MS analysis showed that the Papp (apparent permeability coefficient, 10 –6 cm/s) of phenolics in digested MLs ranged from 0.002 ± 0.00 (quercetin 3- O -glucoside) to 60.19 ± 0.67 (ferulic acid), indicating higher phenolic acids absorbability and poor flavonoids absorbability. The Papp values of phenolic extracts of F-MLs in Caco-2 monolayer were significantly higher (p > 0.05) than that of U-MLs. Digested phenolic extracts inhibited the activities of sucrase (60.13 ± 2.03%) and maltase (82.35 ± 0.78%) and decreased 9.28 ± 0.84% of glucose uptake in Caco-2 monolayer. Furthermore, a decrease in the mRNA expression of glucose transporters SGLT1 (0.64 ± 0.18), GLUT2 (0.14 ± 0.02) and the sucrase-isomaltase (0.59 ± 0.00) was observed. In Caco-2/insulin-resistant HepG2 co-culture model, phenolic extracts regulated glucose metabolism by up-regulating the mRNA expressions of IRS1 (9.32-fold), Akt (17.07-fold) and GYS2 (1.5-fold), and down-regulating the GSK-3β (0.22-fold), PEPCK (0.49-fold) and FOXO1 (0.10-fold) mRNA levels. Both U-MLs and F-MLs could improve glucose metabolism, and the partial least squares (PLS) analysis showed that luteoforol and p -coumaric acid were the primary phenolics that strongly correlated with the hypoglycemic ability of MLs. Results suggested that phenolics of MLs can be used as dietary supplements to regulate glucose metabolism.
研究领域:
药理学
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营养学
·
生物化学
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分子生物学
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细胞生物学
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XENOBIOTICA
·
2026
·
IF 1.5
Jia Yao,Shunjun Yang,Ying Liu,Rong Ye,Yufen Liao,Yong Guo,Rong Tan,Tiantai Wu,Yang Jin,Gangyan Yu,Chang Lin,Weiwei Li,Shiyu Zhang,Jia Yu
Quantitative analytical method was developed for six coumarin constituents in Angelicae pubescentis radix (APR), and the inhibitory effect of the herb’s extract on cytochrome P450 enzymes was investigated.A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of six coumarins (imperatorin, 8-methoxypsoralen, isopimpinellin, isoimperatorin, bergapten, and cnidilin) in APR. Concurrently, the inhibitory effects of its aqueous extract on multiple P450s were evaluated in rat liver microsomes using a ‘Pittsburgh cocktail’ approach.The method demonstrated excellent linearity (R2 > 0.999), precision, stability, repeatability (RSD < 3.0%), and recovery (95.15-102.36%). The extract exhibited significant time-dependent inhibition of CYP1A2 (residual activity 58.2%), with weaker effects on other P450s.A robust LC-MS/MS method was successfully established. The extract of APR was identified as a potent time-dependent inhibitor of CYP1A2 in rat liver microsomes (RLMs), suggesting a potential risk for metabolism-based drug interactions in rats that warrants further investigation in human systems.
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JOURNAL OF SEPARATION SCIENCE
·
2019
·Vol. 42
·期 16
·2668-2678
·
IF 2.516
Ruijuan Liu,Fang Zhao,Jingyao Wei,Pei Yu,Ji Zhang,Yueqin Wang,Zeyun Li,Jiali Zhang,Xiaojian Zhang,Xin Tian
Ribonucleic acid N 6 -methyladenosine methylation plays an important role in a variety of biological processes and diseases. Acetaminophen-induced hepatotoxicity is one of the major challenges faced by clinicians. To date, the link between N 6 -methyladenosine and acetaminophen-induced hepatotoxicity has not been studied. In this study, a simple ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of five nucleosides (adenosine, uridine, cytidine, guanosine, and N 6 -methyladenosine) in messenger ribonucleic acid. After enzymatic digestion of messenger ribonucleic acid, the nucleosides sample was separated on an Acquity UPLC column with gradient elution using methanol and 0.02% formic acid water, and detected by a Qtrap 4500 mass spectrometer with an electrospray ionization mode. The method was validated over the concentration ranges of 4–800 ng/mL for adenosine, uridine, cytidine, and guanosine and 0.1–20 ng/mL for N 6 -methyladenosine. It was successfully applied to the determination of N 6 -methyladenosine levels in liver messenger ribonucleic acid in an acetaminophen-induced hepatotoxicity mouse model and a control group. This study offers a method for the determination of nucleoside contents in epigenetic studies and constitutes the first step toward the investigation of ribonucleic acid methylation in acetaminophen-induced hepatotoxicity, which will facilitate the elucidation of its mechanism.
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JOURNAL OF CHROMATOGRAPHIC SCIENCE
·
2021
·Vol. 59
·期 6
·510-520
·
IF 1.618
Xue Ying,Wang Ziteng,Cai Weimin,Tian Xin,Liu Shuaibing
Ticagrelor is recommended for management of patients with acute coronary syndromes. Green tea is one of the most popular beverages in China and around the world. Their concomitant use is unavoidable. In this study, a selective and sensitive liquid chromatography–tandem mass spectrometry method for the simultaneous determination of plasma concentrations of ticagrelor, its two metabolites and four major constituents of tea polyphenols (TPs) in rats was developed for co-administration study of ticagrelor and TPs. Diazepam was used as internal standard (IS). Plasma samples were extracted employing a liquid–liquid extraction technique. Chromatographic separation was carried out on a Kinetex C18 column (2.1 × 75 mm, 2.6 μm) by gradient elution using 0.1% formic acid in water, acetonitrile and methanol. Seven analytes and IS were detected by a mass spectrometer with both positive and negative ionization by multiple reaction monitoring mode. The method was fully validated to be reliable and reproducible in accordance with food and drug administration (FDA) guidelines on bioanalytical method validation. The method was then successfully applied for pharmacokinetic study of ticagrelor, its two metabolites and four major constituents of TPs in rat plasma after oral administration of ticagrelor and tea polyphenol extracts.
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XENOBIOTICA
·
2024
·
IF 1.3
Li Shao,Jiajia Mo,Qinlong Xu,Guangwei He,Chunyu Xing,Zhaoxing Chu
HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC–MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1–7.6% after transdermal application of 1–4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug.
研究领域:
药理学
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皮肤病学
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2021
·
IF 3.205
Xiangling Feng,Yufeng Ding,Peng Zhang,Qiang Fu,Li Zhang,Heng Zheng
Dacomitinib, an irreversible pan-ErbB tyrosine kinase inhibitor targeting the human epidermal growth factor receptor, is used for the treatment of metastatic non-small cell lung cancer. To facilitate the investigations on its metabolism and other relevant studies, based on high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS), a rapid and sensitive bioanalytical technique was established and fully validated for simultaneous quantification of dacomitinib and its main metabolite in human plasma. The plasma samples were treated with acetonitrile containing 0.1% formic acid and the liquid supernatant was collected, dried and dissolved in methanol-water-formic acid (200:800:1, v/v) before injection. The chromatographic separation was performed on an ACE Excel C 18 column (2.1 mm × 50.0 mm, i.d., 5 μm) by gradient elution with a mixture of buffer (5 mM ammonium acetate in 0.1% formic acid) and acetonitrile, serving as the mobile phase, with an overall run time of 4 min. Dacomitinib, O-desmethyl dacomitinib and IS were subsequently detected on an AB QTRAP 5500 mass spectrometer in positive ion and multiple reaction monitoring modes at the precursor-to-product transitions of m / z 470.4 → 385.0, m / z 456.0 → 370.9 and m / z 480.2 → 385.1, respectively. The accuracy and precision of determinations were guaranteed within the concentration ranges of 0.25–100 ng/mL for dacomitinib and 0.20–80 ng/mL for O-desmethyl dacomitinib. The intra- and inter-assay accuracy ranged from 92.00% to 104.50% and the intra- and inter-assay precision was less than 8.20% for each analyte. The method was validated and the relevant parameters, including selectivity, interference among analytes and internal standard, carry-over effect, dilution integrity, extraction recovery, matrix effect, and stability, all satisfied the requirements formulated by the US Food and Drug Administration and the European Medicines Agency. The clinical applicability of the fully-validated method was evaluated in medicated samples from patients on dacomitinib.
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BIOMEDICAL CHROMATOGRAPHY
·
2016
·Vol. 30
·期 11
·1796-1806
·
IF 1.729
Junjun Ni,Li Xu,Wei Li,Lijun Wu
Easy-to-use early cancer detection methods based on metabolomics using serum samples have been developed recently. Among metabolites, amino acids and acylcarnitine are two of the most suitable candidates for diagnosing lung cancer. The purpose of the present study was to develop a novel, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to simultaneously determine 13 amino acids and 8 acylcarnitines in lung cancer patients in serum. After derivatization, the 21 analytes were separated using a C 18 column with gradient elution program in 14 min, obtaining recovery within 90.4–113.8% and precision within 0.3–14.8%. The method was successfully applied in concentration determination of lung cancer patients and healthy controls. The results showed that the serum concentration of lung cancer patients were significant from those of healthy controls.
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FOOD CHEMISTRY
·
2025
·
IF 9.8
Zi-Ling Li,Da-Jin Yang,Jia-Qi Zhao,Wen-Jie Sun,Jie Gao,Shu-Feng Song,Hou-Jun Xu,Hai-Jie Li,Fa-Ming Tian,Man-Man Wang
A novel magnetic nanoporous carbon (Fc-Fe/Ni@MPC) was fabricated from ferrocene contained metal-organic framework (MOF) and employed as multifunctional QuEChERS adsorbent for determination of triazine herbicides in various fruit and vegetable samples before LC-MS/MS. The prepared Fc-Fe/Ni@MPC not only maintained the original ordered morphology from MOF precursor, but also exhibited high graphitization and good superparamagnetism through pyrolysis. This sorbent afforded adsorption capacity of 1163.25 mg/g, 157.83 mg/g, 157.69 mg/g and 25.10 mg/g towards chlorophyll, lycopene, β -carotene and lutein via hydrophobic, π-π and hydrogen bonding interactions. The method gave negligible matrix effects of −14.2 % ∼ 10.8 %, low detection limits of 0.001–0.04 μg/kg and satisfactory recoveries of 80.2 %–112 % in orange, citrus, apple, watermelon, tomato, carrot and lettuce samples, when performing 2 mg of this single sorbent within just 15 s. This work revealed the prospect of Fc-Fe/Ni@MPC as versatile and efficient QuEChERS adsorbent for pretreatment of triazine herbicides in large kinds of pigment-rich food samples.
研究领域:
分析化学
·
食品科学
·
环境科学
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BIOMEDICAL CHROMATOGRAPHY
·
2024
·Vol. 38
·期 12
·e6034
·
IF 1.8
Feng Chen,Huanhuan Li,Xiaoxia Yang,Ziwei Deng,Hongqiang Wang,Zhihua Shi,Chengfeng Qiu
To facilitate clinical therapeutic drug monitoring (TDM) of polymyxin B (PB) and polymyxin E (PE), we developed and validated a simple LC–MS/MS method for simultaneous determination of PB (including polymyxin B1 (PB1), polymyxin B2 (PB2), polymyxin B3 (PB3) and isoleucine-polymyxin B1 (ile-PB1)) and PE (including polymyxin E1 (PE1) and polymyxin E2 (PE2)) in human plasma. PB or PE was extracted from 20.0 μL plasma using a 5% (v/v) formic acid acetonitrile solution and separated on a BEH-C18 column (2.1 × 100 mm, 1.7 μm) with a mobile phase consisting of 0.8% formic acid aqueous solution and 0.2% formic acid acetonitrile solution. Gradient elution was performed over 5.5 min at a flow rate of 0.250 mL/min. Quantitative analysis was conducted in positive ion scanning mode by electrospray ionization and multiple reaction monitoring. The method validation was conducted based on bioanalytical method validation guidance, including specificity, calibration curve, precision, accuracy, recovery, matrix effect, stability and dilution integrity and all of the results satisfied the requirements. The method was simple, robust and high-throughput and is currently being used to provide a TDM service to enhancing therapeutic efficacy and safety use of the PB and PE.
研究领域:
分析化学
·
临床医学
·
药理学
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