ACS Omega
·
2025
·
IF 4.3
Tingting Lou,Benkai Qin,Jiaqi He,Hongliu Qu,Haiyan Rong,Qunan Cheng,Weiyong Lu,Yaqin Liu,Yonghua Yu
A rapid, specific, and sensitive LC–MS/MS method for the determination of sulindac and its metabolite Su-EP-C in human EDTA-K2 plasma was developed. The method was fully validated using sulindac-d3 and Su-EP-C-d3 as internal standards. Separation was performed on a Kinetex C18 analytical column (100 Å, 50 × 2.1 mm, 5 μm). MPA consisted of 0.05% formic acid (FA) in water, while MPB comprised 0.05% FA in ACN. The flow rate was maintained at 0.300 mL/min, and the injection volume was 3 μL. Mass spectrometry conditions: ESI, positive mode, MRM. The linear range of detection was from 60.00 to 24,000.00 ng/mL for sulindac and from 30.00 to 12,000.00 ng/mL for Su-EP-C. The intra- and interbatch accuracy deviations of sulindac ranged from −5.1 to 5.0%, and the intra- and interbatch precision ranged from 3.3 to 4.2%. The intra- and interbatch accuracy of Su-EP-C ranged from −3.9 to 6.9%, and the intra- and interbatch precision ranged from 4.8 to 7.2% at all concentration levels. At a dilution of 10, the deviation for sulindac was 3.5% and the precision was 1.5%; the deviation for Su-EP-C was 2.7%, and the precision was 4.4%. The plasma matrix, at both −20 °C and −70 °C, remained stable for 52 days with 5 freeze–thaw cycles. The method was successfully applied to fasting and postprandial pharmacokinetic clinical trials of orally administered sulindac tablets.
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高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2014
·
IF 2.829
Feng Chen,Hai-Long Li,Yin-Feng Tan,Yong-Hui Li,Wei-Yong Lai,Wei-Wei Guan,Jun-Qing Zhang,Yuan-Sheng Zhao,Zhen-Miao Qin
Alpinia oxyphylla (Yizhi) capsularfruits are commonly used in traditional medicine. Pharmacological studies have demonstrated that A. oxyphylla capsularfruits have some beneficial roles. Besides volatile oil, sesquiterpenes, diarylheptanoids and flavonoids are main bioactive constituents occurring in the Yizhi capsularfruits. The representative constituents include tectochrysin, izalpinin, chrysin, apigenin-4′,7-dimethylether, kaempferide, yakuchinone A, yakuchinone B, oxyphyllacinol and nootkatone. Their content levels in the fruit and its pharmaceutical preparations have been reported by our group. The nine phytochemicals are also the major components present in the Yizhi alcoholic extracts, which have anti-diarrheal activities. However, the fates of these constituents in the body after oral or intravenous administration remain largely unknown. In the present study, we focus on these phytochemicals albeit other concomitant compounds. The chemicals and their metabolites in rat plasma were identified using liquid chromatography/tandem mass spectrometry with selected reaction monitoring mode after orally administered Yizhi extract to rats. Rat plasma samples were treated by methanol precipitation, acidic or enzymatic hydrolysis. This target analysis study revealed that: (1) low or trace plasma levels of parent chemicals were measured after p.o. administration of Yizhi extract, Suoquan capsules and pills to rats; (2) flavonoids and diarylheptanoids formed mainly monoglucuronide metabolites; however, diglucuronide metabolites for chrysin, izalpinin and kaempferide were also detected; (3) metabolic reduction of Yizhi diarylheptanoids occurred in rats. Yakuchinone B was reduced to yakuchinone A and then to oxyphyllacinol in a stepwise manner and subsequently glucuronidated by UDP-glucuronosyl transferase. Further research is needed to characterize the UDP-glucuronosyl transferase and reductase involved in the biotransformation of Yizhi chemicals.
研究领域:
药理学
·
分析化学
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Analytical Methods
·
2016
·Vol. 8
·期 9
·2069-2081
·
IF 1.915
Qi Wen,Hai-Long Li,Yin-Feng Tan,Xu-Guang Zhang,Zhen-Miao Qin,Wei Li,Yong-Hui Li,Jun-Qing Zhang,Feng Chen
Alpiniae oxyphyllae Fructus (Yizhi in Chinese) is commonly used for the treatment of diarrhea, intestinal disorders and urinary incontinence symptoms. To date, little information is available on the pharmacokinetic (PK) properties of this herb. We have identified the known active chemicals (including nootkatone, yakuchinone A, yakuchinone B, oxyphyllacinol, tectochrysin, chrysin, izalpinin, apigenin-4′,7-dimethylether, and kaempferide) and their metabolites (phase II metabolites and oxidized product such as kaempferol) from Yizhi extract in rat plasma using liquid chromatography/tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring. In the present study, an LC-MS/MS-based method was developed and validated for the simultaneous quantitation of the Yizhi chemicals and their metabolites in rat plasma after enzymatic treatment. A mixture of β-glucuronidase and sulfatase was used to liberate parent chemicals from their phase II metabolites. A post-extraction spike method, as well as a post-column infusion method, was conducted to investigate matrix-effects. Particularly, the ion suppression effect for all the analytes was overcome through combining a liquid–liquid extraction method for clean-up, elution gradient optimization for separation and inclusion of very low concentration of HCOOH into the mobile phase. Mean accuracies were obtained in the range of 84.7–112% at three different quality control levels for the ten analytes, with intra- and inter-day variations within 13.6% (1.76–13.6%). This validated method was successfully applied to a PK investigation in rats after a single oral administration of Yizhi extract. These results supply a suitable reference for further PK studies of the Yizhi chemicals and their metabolites in the future.
研究领域:
中药学
·
分析化学
·
药理学
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2026
·
IF 3.4
Hui Yan,Haoyang Lu,Shanqing Huang,Yuqing Li,Hui Xia,Wanting Huang,Dewei Shang,Ming Zhang
Dysregulation of the tryptophan (TRP) metabolic pathway is closely linked to the pathophysiology of neuropsychiatric disorders, such as depression. This study aimed to develop and validate a sensitive, rapid, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of TRP and its metabolites, kynurenine (KYN) and kynurenic acid (KYNA), in human serum. Analytes were extracted from 100 µL of serum via simple protein precipitation with acetonitrile. Chromatographic separation was achieved on an Agilent ZORBAX HILIC Plus column (4.6 mm×100 mm, 3.5 µm) using isocratic elution with a mobile phase of methanol: acetonitrile containing 5 mM ammonium formate. Quantification was performed using an electrospray ionization source in positive ion multiple reaction monitoring (MRM) mode, with a total run time of only 2.0 min.The linear ranges were 1- 50 µg/mL for TRP, 0.1-5 µg/mL for KYN, and 1-50 ng/mL for KYNA, covering clinically relevant levels. A weighting factor of 1/x² provided the best fit for calibration curves (R² > 0.99). Extraction recoveries ranged from 88.23% to 99.39%, and mean internal standard-normalized matrix effects were 81%-100%. Accuracy and precision values met bioanalytical acceptance criteria. Stability assessments confirmed that samples were stable at -20°C and -80°C for 31 days and through three freeze-thaw cycles. This validated method was successfully applied to analyze serum samples from 103 adolescent patients with first-episode depression.
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JOURNAL OF SEPARATION SCIENCE
·
2020
·Vol. 43
·期 13
·2718-2727
·
IF 2.878
Xiu-Fang Yan,Yan-Mei Liang,Bo Zhou,Jun Bin,Chao Kang
The high selectivities of liquid chromatography and mass spectrometry make liquid chromatography–mass spectrometry one of the most popular tools for quantitative analysis in complex chemical, biological, and environmental systems, while the potential mathematical selectivity of liquid chromatography–mass spectrometry is rarely investigated. This work discussed the mathematical selectivity of liquid chromatography–mass spectrometry by three-way calibration based on the trilinear model, with an application to quantitative analysis of coeluting aromatic amino acids in human plasma. By the trilinear decomposition of the constructed liquid chromatography–mass spectrometry-sample trilinear model and individual regression of the decomposed relative intensity versus concentration, the proposed three-way calibration method successfully achieved quantitative analysis of coeluting aromatic amino acids in human plasma, even in the presence of uncalibrated interferent(s) and a varying background. This analytical method can ease the requirements for sample preparation and complete chromatographic separation of components, reduce the use of organic solvents, decrease the time of chromatographic separation, and increase the peak capacity of liquid chromatography–mass spectrometry. As a “green analytical method”, the liquid chromatography–mass spectrometry three-way calibration method can provide a promising tool for direct and fast quantitative analysis in complex systems containing uncalibrated spectral interferents, especially for the situation where the coelution problem is difficult to overcome.
研究领域:
分析化学
·
生物医学
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高影响因子
JOURNAL OF ONCOLOGY PHARMACY PRACTICE
·
2022
·
IF 1.416
Hailong Zhou,Yunyun Li,Fan Xu
PurposeOccupational exposure is a long-standing public health concern, which has drawn more and more attention in recent years to the problem of how to carry out occupational protection effectively. Gloves are regarded as the most critical protective equipment for cytotoxic medications. However, there is still little research conducted on the protective performance of gloves made of different materials and the optimal glove combination for cytotoxic agents.MethodsIn this research, a specific instrument intended for glove permeation experiment was designed, with various methods of liquid chromatography-tandem mass spectrometry (LC-MS/MS) developed and validated. By using the specific instrument and LC-MS/MS methods, a study was conducted on the permeation ability of eight selected cytotoxic drugs (fluorouracil, epirubicin (EPI), docetaxel (DCT), methotrexate (MTX), cyclophosphamide (CTX), etoposide (ETP), vincristine sulfate (VCR), and cisplatin derivatives Pt-(DDTC)3) into five kinds of gloves (rubber (RB), nitrile (NT), chlorinated polyethylene (CPE), low-density polyethylene, and polyvinylchloride (PVC) resin) given different contact times. Then, the experimental data were analyzed through a generalized estimation equation and Pearson correlation analysis.ResultsThe results show that within a short period of time (less than five minutes), ETP, CTX, fluorouracil, DCT, and cisplatin passed through five types of gloves but the level of MTX, VCR, and EPI permeation was minimal, despite the duration of contact between the three drugs and the gloves reaching as long as three hours. Furthermore, the permeation of DCT and ETP was found to be positively correlated with time.ConclusionsChlorinated polyethylene and PVC resin perform well in protecting against most cytotoxic drugs and are recommendable for clinical practice. Due to the poor protective ability, RB gloves are not recommended for this purpose. Based on the performance of various gloves in offering protection, the protection grade of two gloves can be deduced. Chlorinated polyethylene + PVC resin, CPE + NT glove combination shows good protective performance against most target drugs and can be recommended for clinical practice.
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JOURNAL OF SEPARATION SCIENCE
·
2021
·Vol. 44
·期 7
·1391-1403
·
IF 3.645
Ning Wang,Yue-Wu Xie,Meng-Yu Li,Fei-Fei Li,Li-Yuan Zhang,Yu-Lin You,Shu-Qi Wang
Rauvolfia vomitoria is widely distributed in the tropical regions of Africa and Asia, and has been used in traditional folk medicine in China. Indole alkaloids were found to be major bioactive components, while the effects of diabetes mellitus on the pharmacokinetic parameters of the components have not been reflected in vivo. In this study, an efficient and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of five ingredients of R. vomitoria in rats. Detection was implemented in multiple-reaction-monitoring mode with an electrospray positive-ionization source. Validation parameters were all in accordance with the current criterion. The established method was effectively employed to compare the pharmacokinetic behaviors of five alkaloids (reserpine, yohimbine, ajmaline, ajmalicine, and serpentine) between normal and type 2 diabetic rats. The single-dose pharmacokinetic parameters of the five alkaloids were determined in normal and diabetic rats after oral administration of 100 and 200 mg/kg body weight. The results indicated that diabetes mellitus significantly altered the pharmacokinetic characteristics of yohimbine, ajmaline, and ajmalicine after oral administration in rats. This is an attempt to provide some evidence for clinicians that may serve as a guide for the use of antidiabetic medicine in clinical practice.
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2018
·
IF 2.441
Lihan Sun,Huajing Wu,Lianjie Ren,Jiaojiao Cong,Xiaohui Qin,Xingli Wang,Xinming Qi,Lifeng Kang,Junying Zhang,Chunyong Wu
A sensitive and specific liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitative analysis of 1,2:5,6-dianhydrogalactitol (DAG) in mouse plasma and tissues. Sodium diethyldithiocarbamate (DDTC) was used as the derivatization reagent to improve its LC-MS/MS behavior. Analytes were separated on a Welch Ultimate XB-CN column with a mobile phase consisting of acetonitrile and 0.1% formic acid solution (65:35). The MS analysis was conducted by positive electrospray ionization in multiple-reaction monitoring (MRM) mode. Good linearity (r 2 > 0.9958) was observed over the concentration range of 1–1000 ng/mL in plasma and tissue homogenates (brain, liver, heart, spleen, lung and kidney). The intra- and inter-batch precision and accuracy of DAG in plasma and brain samples were all within the acceptable limits. The extraction recovery was stable and no significant matrix effects were observed. The method was successfully applied to study the pharmacokinetic and tissue distribution of DAG in mice after intravenous administration. DAG could cross the blood-brain barrier and had limited liver distribution. Rat primary hepatocytes in vitro experiments demonstrated that DAG had a safe profile in liver.
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高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6063
·
IF 1.7
Fan Tang,Xiaoli Hou,Jiajie Chen,Yasen Cao,Yixia Wang,Hong Cheng
Mobocertinib is a potent selective tyrosine kinase inhibitor approved for the treatment of non–small cell lung cancer with activating EGFR exon 20 insertions. The aim of this study was to develop a procedure for liquid chromatography tandem mass spectrometry (LC-MS/MS) for the determination of mobocertinib and its metabolite desmethyl-mobocertinib in human plasma. The human plasma samples were precipitated with acetonitrile and analyzed using a Waters ACQUITY BEH C 18 column coupled to a triple quadrupole mass spectrometer. Separation was executed using the acetonitrile–0.1% formic acid solution with gradient elution, at a flow rate of 0.4 mL/min. Mobocertinib and desmethyl-mobocertinib were monitored by multiple reaction monitoring (MRM) with m / z 586.5 > 72.2 and 572.4 > 473.2, respectively. The procedure demonstrated excellent linearity ( r > 0.997) within the concentration range of 0.1–200 ng/mL for both analytes. Precision in relative standard deviation was < 9.37% for mobocertinib and < 12.03% for desmethyl-mobocertinib. Accuracy in relative error was within −7.23% to 9.18% for mobocertinib and −2.78% to 9.87% for desmethyl-mobocertinib. Extraction recovery was > 80% for both analytes. The validated LC-MS/MS method was successfully applied to the pharmacokinetic study of mobocertinib and desmethyl-mobocertinib in healthy human volunteers with K 2 EDTA as anticoagulant after a single dose of mobocertinib (160 mg).
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JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Jie Li,Xiaolong Lian,Baojian Li,Quhuan Ma,Lingling Yang,Guangmiao Gao,Tingmei Yin,Xiaoyan Fu,Yi Deng,Zhijun Yang,Xiujuan Yang
Ethnopharmacological relevance Cisplatin (CP), a widely used antineoplastic agent, is a leading cause of drug-induced liver injury (DILI) due to its hepatotoxic effects. Licorice (GC), an established remedy in traditional Chinese medicine (TCM), has shown promise in addressing liver diseases and DILI. Nonetheless, the specific active components and underlying mechanisms of GC in mitigating CP-induced liver injury remain inadequately investigated. Aim of the study This study examined the active components and efficacy of GC in addressing CP-induced hepatotoxicity, focusing on its mechanisms related to bile acid metabolism and gut microbiota regulation. Materials and methods Utilizing a CP-induced rat liver injury model, this study evaluated changes in liver coefficient, liver function indices, and pathological morphology while assessing the efficacy of GC for both prevention and treatment of CP-induced liver injury. Subsequently, UPLC-Q-TOF-MS qualitatively analyzed GC's blood-entering components, elucidating its pharmacodynamic material basis. Network pharmacology analysis identified potential pathways and targets of GC's blood components in relation to CP-induced liver injury. Furthermore, metabolomics and 16S rRNA sequencing were employed to clarify the pharmacodynamic mechanisms of GC in modulating bile acid metabolism and gut microbiota, offering insights into its preventive and therapeutic roles. Results The pharmacodynamic results revealed that GC significantly reduced liver function biomarkers and improved pathological changes in liver tissue. UPLC-Q-TOF-MS analysis identified 16 blood-entering components as potential pharmacodynamic agents of GC for preventing and treating CP-induced liver injury. Network pharmacology analysis suggested a link between GC's efficacy and the bile acid metabolic pathway. Furthermore, metabolomics analysis, immunoblotting, and 16S rRNA sequencing demonstrated that GC regulated bile acid metabolites in both liver and feces, enhanced FXR and BSEP expressions in the liver, and decreased CYP27A1 expression. Additionally, GC mitigated CP-induced intestinal dysbiosis by altering the abundance of gut microbiota. Conclusions UPLC-Q-TOF-MS performed a qualitative analysis of 16 blood-entering components linked to GC, providing a basis for further exploration of the pharmacodynamic material underpinning GC. The protective role of GC in CP-induced liver injury appears connected to enhanced bile acid metabolism and restoration of gut microbiota balance.
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高影响因子
BMC Pregnancy and Childbirth
·
2026
·Vol. 26
·期 1
·1124
·
IF 3.1
Bai Mengru,Shen Qian,Wu Yong,Chen Mingyang,Liu Dan,Lin Nengming,Zhang Wei
Background Uncontrolled hyperglycemia in pregnancy poses risks to both mother and fetus, but treatment options are limited. Sitagliptin, vildagliptin, linagliptin, and alogliptin are dipeptidyl peptidase-4 (DPP-4) inhibitors effective in type 2 diabetes. However, data on their placental transfer and safety in pregnant women is lacking. Therefore, this study compared the permeability of these drugs in multiple placental cell models, including BeWo, HTR-8/SVneo, and primary human trophoblast cells, and attempted to explore their transport mechanisms. Methods A cost-effective liquid chromatography-tandem mass spectrometry method was developed and validated to quantify the four DPP-4 inhibitors. The accumulation of these drugs in placental cell models was compared, and the BeWo Transwell transport assay was conducted to assess transport rates. Transporter inhibitors, siRNA knockdown, and transporter overexpression cell models were used to explore the transmembrane transport mechanism of these drugs. Results Linagliptin had the highest accumulation in placental cells, followed by alogliptin, sitagliptin, and vildagliptin. The apparent permeability coefficient of linagliptin, alogliptin and sitagliptin was similar in BeWo cells, while vildagliptin was the lowest. The accumulation of linagliptin, alogliptin, sitagliptin and vildagliptin in BeWo cells at 37 °C were significantly higher than those at 4 °C, indicating the presence of carrier-mediated uptake. However, studies using transporter inhibitors, siRNA knockdown, and transporter overexpression cell models showed that equilibrative nucleoside transporters (ENTs), concentrative nucleoside transporters (CNTs), and organic anion transporter (OAT) 4 do not facilitate the placental transfer of linagliptin, alogliptin, sitagliptin, and vildagliptin. Conclusions Vildagliptin had the lowest accumulation and permeability in placental cells among the four DPP-4 inhibitors. There might be carrier-mediated transmembrane transport of linagliptin, alogliptin, sitagliptin and vildagliptin, but ENTs, CNTs and OAT4 were not involved in. This study provides a basis for future research on their safety during pregnancy. Graphical
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FOOD CHEMISTRY
·
2026
·
IF 9.8
Yawen He,Chengxun Lin,Bin Zhang,Zixuan Wang,Jiangui Li,Zhenfan Yu
Fuji apples from the Aksu production region are highly favored by consumers. In contrast, those from the Yili region exhibit marked differences in flavor profiles, the mechanisms of which remain unclear. This study investigated the flavor variations in Fuji apples from these two producing regions by integrating analyses of both volatile and non-volatile metabolites. The results from the electronic nose and electronic tongue indicated that the sensors for W1W, W2W, W5S, and sourness exhibited the most pronounced responses in Fuji apples from the Aksu region. 16 key aroma-active compounds and 143 non-volatile differential compounds were identified. The aroma of Fuji apples was predominantly characterized by esters and terpenoids, with representative compounds including hexyl 2-methylbutanoate, 3-Methylbutyl acetate, 2-Methylbutyl acetate, and citronellol. These compounds collectively impart fruity, sweet, and floral notes. Furthermore, the peel of the ‘Yanfu 6’ cultivar from Aksu exhibited distinctive rosy and woody notes, while its pulp possessed a pineapple-like aroma. KEGG pathway enrichment analysis demonstrated that amino acid metabolism, fatty acid metabolism, and phenylalanine metabolism are interconnected. This study provides valuable insights for systematically understanding the formation of characteristic aromas in Fuji apples from the Xinjiang region
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高影响因子
危险品化学品经营许可证（带存储）