PeerJ
·
2021
·
IF 2.984
Rangru Liu,Hailong Li,Na Wei,Yinfeng Tan
Galangin has multiple pharmacological efficacies, such as anti-cancer, anti-inflammation and anti-oxidation. Galangin can be rapidly converted into glucuronidated metabolites in vivo. This study aimed to establish an UFLC-MS/MS analytical method to simultaneously determine the concentrations of two glucuronidated metabolites of galangin, galangin-3-O-β-D-glucuronic acid (GG-1) and galangin-7-O-β-D-glucuronic acid (GG-2) in rat plasma. After oral administration of galangal extract (0.3 g/kg), blood samples were collected from the orbital sinus, then treated by methanol precipitation and further gradient-eluted with Phenomenex Kinetex 2.6 µm XB-C18 column. The mass spectrometer was manipulated in the negative electrospray ionization (ESI) and selected multiple reaction monitoring (MRM) mode for the analytes. The precursor-to-product ion pairs applied for GG-1, GG-2 and chrysin (as the internal standard, IS) were m/z 445.2→269.0, 445.2→268.9 and 253.0→142.9, respectively. The results showed that the linear ranges for both GG-1 and GG-2 were 2.0–2000.0 ng/mL ( r 2 > 0.995). The inter- and intra-day precision were 89.3%–109.2%, RSD was less than 15%, and the repeatability was good. The recoveries of both metabolites and IS were over 89%, and matrix effect was within 15%. The validated analytical method was further applied to study the pharmacokinetic profiles of GG-1 and GG-2 in vivo. The pharmacokinetic parameters suggested that T max of GG-1 was equivalent to that of GG-2, and MRT 0-t , t 1/2 of GG-2 were a little higher than those of GG-1. Importantly, AUC 0-t and C max of GG-2 were almost twice as those of GG-1. In short, the validated UFLCMS/MS analytical method was feasible to simultaneously determine two galangin metabolites GG-1 and GG-2 in rat plasma and further analyze in vivo metabolism of galangin.
研究领域:
药物分析
·
药理学
·
生物化学
✓ 已验证
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2018
·
IF 2.441
Yilin Sun,Le Zhen,Ying Peng,Jiankun Wang,Fei Fei,Lixiang Aa,Wenjiao Jiang,Xue Pei,Li Lu,Jie Liu,Guangji Wang,Kun Hao
To improve bioavailability and provide resistance to deamination , an array of gemcitabine (dFdC) prodrugs carrying the acyl modifications has been successful in the optimization of pharmacokinetic properties of dFdC, but the reports about 4- N -carbobenzoxy-dFdC (Cbz-dFdC), a dFdC prodrug bearing alkyloxycarbonyl modification, are relatively rare. Notably, in vivo enzymatic hydrolysis was an absolutely essential factor for the activation of these prodrugs, which is correlated with the anti-tumor activity. Therefore, detailed metabolism studies of Cbz-dFdC should be carried out for a more authentic pharmacodynamic evaluation. In order to detect the pharmacokinetic characteristics of Cbz-dFdC, a selective, sensitive and accurate method for the simultaneous determination of Cbz-dFdC, along with dFdC and its major metabolite dFdU in rat plasma was developed and validated using UFLC–MS/MS techniques. Column was at 40 °C for separation using an eluent with acetonitrile and 0.1% formic acid , 1 mM ammonium formate at a flow rate of 0.2 mL/min. Detection was performed using ESI source in positive ion selected reaction monitoring mode by monitoring the following ion transitions m / z 398.1 → 202.2 (Cbz-dFdC), m / z 264.1 → 112.0 (dFdC), m / z 265.3 → 113.2 (dFdU) and m / z 246.1 → 112.0 (IS). Analytes were extracted by simple precipitation with acetonitrile containing internal standards followed by liquid-liquid extraction with ethyl acetate . The calibration curves of Cbz-dFdC, dFdC and dFdU were linear in the concentration range of 2 to 500 ng/mL, 2 to 500 ng/mL and 40 to 10,000 ng/mL, respectively. The assay ranges selected for the three analytes were appropriate and minimized the need for reanalysis. All the validation data, such as intra- and inter-day precision, accuracy, selectivity and stability, were within the required limits. In conclusion, the sensitive analytical assay was selective and accurate for the determination of rat plasma concentrations of Cbz-dFdC, dFdC and dFdU from a single LC–MS/MS analysis and well-suited to support pharmacokinetic studies.
研究领域:
药物化学
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分析化学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2014
·Vol. 19
·期 4
·4510-4523
·
IF 2.095
Feng Chen,Hai-Long Li,Yin-Feng Tan,Wei-Wei Guan,Jun-Qing Zhang,Yong-Hui Li,Yuan-Sheng Zhao,Zhen-Miao Qin
Plant secondary metabolites are known to not only play a key role in the adaptation of plants to their environment, but also represent an important source of active pharmaceuticals.Alpinia oxyphyllacapsular fruits, made up of seeds and pericarps, are commonly used in traditional East Asian medicines. In clinical utilization of these capsular fruits, inconsistent processing approaches (i.e., hulling pericarps or not) are employed, with the potential of leading to differential pharmacological effects. Therefore, an important question arises whether the content levels of pharmacologically active chemicals between the seeds and pericarps ofA. oxyphyllaare comparable. Nine secondary metabolites present inA. oxyphyllacapsular fruits, including flavonoids (e.g., tectochrysin, izalpinin, chrysin, apigenin-4',7-dimethylether and kaempferide), diarylheptanoids (e.g., yakuchinone A and B and oxyphyllacinol) and sesquiterpenes (e.g., nootkatone), were regarded as representative constituents with putative pharmacological activities. This work aimed to investigate the abundance of the nine constituents in the seeds and pericarps ofA. oxyphylla. Thirteen batches ofA. oxyphyllacapsular fruits were gathered from different production regions. Accordingly, an ultra-fast high performance liquid chromatography/quadrupole tandem mass spectrometry (UFLC-MS/MS) method was developed and validated. We found that: (1) the nine secondary metabolites were differentially concentrated in seeds and fruit capsules; (2) nootkatone is predominantly distributed in the seeds; in contrast, the flavonoids and diarylheptanoids are mainly deposited in the capsules; and (3) the content levels of the nine secondary metabolites occurring in the capsules varied greatly among different production regions, although the nootkatone levels in the seeds were comparable among production regions. These results are helpful to evaluating and elucidating pharmacological activities ofA. oxyphyllacapsular fruits. Additionally, it may be of interest to elucidate the mechanisms involved in the distinct accumulation profiles of these secondary metabolites between seeds and pericarps.Keywords:secondary metabolites;A. oxyphyllacapsular fruits;diarylheptanoids;flavonoids;nootkatone;production region;UFLC-MS/MS
研究领域:
药用植物学
·
分析化学
·
传统医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2018
·
IF 2.441
Yi-ran Wang,Yong-hui Li,Tao Guo,Hai-long Li,Yin-feng Tan,Zhong Zhang,Xu-guang Zhang,Shi-ying Mai,Jun-qing Zhang
The compounds of N-Methylanhydrotetrahydroberberrubine A, dictamnine and eudesmin were the primary bioactive components in the roots of Zanthoxylum armatum DC ( Z . armatum ). To clarify the pharmacokinetics and distribution of these three compounds, an ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was employed to determine the contents of these three compounds in rat plasma and seven tissues. The separation was achieved on a Kinetex XB–C18 100A column (2.1 × 50 mm, 2.6 μm, Phenomenex). The optimized mobile phase system was set with 0.1‰ formic acid aqueous solution (A) and acetonitrile (containing 0.1‰ formic acid) (B) with a programmed elution of 0.00 to 0.50 min, 2% B; 0.51–4.00 min, 30%–60% B; and 4.01–5.00 min, 2% B. All analytes were measured with optimized multiple reaction monitoring (MRM) in the positive ion ESI mode. Berberine hydrochloride was selected as the internal standard (IS). The MS/MS transitions of N-Methylanhydrotetrahydroberberrubine A, dictamnine, eudesmin and IS were 339.9135.1, 200.1 → 129.1, 387.4 → 369.0 and 337.1 → 321.1, respectively. The lower limits quantification (LLOQ) of the three analytes was 0.5–20 ng/ml. The linear ranges were 0.5–400 ng/ml for N-Methylanhydrotetrahydroberberrubine A and dictamnine and 20–4000 ng/ml for eudesmin. The present analysis showed that the two alkaloids were quickly absorbed, with T max in 0.167–0.292 h, and eudesmin was absorbed in 2.5 h. Moreover, all compounds were found at high concentrations in the gastrointestinal track. These results are helpful for further investigation of the clinical application of Z . armatum .
研究领域:
药理学
·
分析化学
·
天然产物研究
·
药学
✓ 已验证
DOI
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
·
2022
·
IF 1.193
Yu-Ye GAO,Xie-An YU,Bing WANG,Li-Fei GU,Yuan-Yuan GE,Guang-Lin ZHU,Kun-Hui SUN,Yi LU,Tie-Jie WANG,Kai-Shun BI
Red wine was famous for the potential effects on coronary heart disease (CHD), but the pharmacokinetic study of the main active compounds was unclear. In this research, a simple, rapid and sensitive ultra-fast liquid chromatography coupled with triple quadrupole mass spectrometry (UFLC-MS/MS) method was established for simultaneous determination of six phenolic acids and six flavonoids after oral administration of red wine in rat plasma. Moreover, the pharmacokinetic differences of the six active compounds in control and CHD model rats after oral administration of red wine were investigated. Rosmarinic acid and puerarin were selected as internal standards. Extraction of plasma sample was by protein precipitation using acetonitrile . An HSS T3 column (1.8 µm, 2.1 mm × 100 mm) was used to separation at a flow rate of 0.3 mL/min with mobile phase consisting of 0.1% formic acid aqueous solution and 0.1% formic acid acetonitrile. The developed method was successfully applied to comparative pharmacokinetic study between control and CHD model rats. The results showed that some pharmacokinetic parameters were significantly different among the control and CHD model rats. Accordingly, it was expected that the results of this study could provide a scientific basis for further exploring red wine for the prevention and treatment of CHD.
研究领域:
药理学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2020
·
IF 3.209
Shi-Kang Zhou,Yi Zhang,Yong-Hui Ju,Qiao Zhang,Da Luo,Yu-Dan Cao,Wei-Feng Yao,Yu-Ping Tang,Li Zhang
The dried roots of Euphorbia kansui (EK) are especially beneficial for the treatment of edema, but the severe toxicity limits their clinical applications. Euphorbia kansui stir-fried with vinegar (VEK) is traditionally employed to reduce the toxicity of EK. However, the material basis for the toxicity reduction with effectivity conservation is still unclear. Therefore, in this study, a rapid, sensitive, and reliable ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was firstly established to simultaneously determine six ingenane-type diterpenoids, i.e. kansuiphorin C (1) , 5- O -benzoyl-20-deoxyingenol (2) , 20-deoxyingenol (3) , 3- O -(2’ E ,4’ E -decadienoyl)-20- O -acetylingenol (4) , 20- O -(2’ E ,4’ Z -decadienoyl)ingenol (5) , and ingenol (6) , in EK and VEK based on the processing conversion. Then, the toxicity evaluation on zebrafish embryos and modulation of the expression of aquaporin-3 (AQP3) proteins in HT-29 cells were employed to investigate the toxicity-activity of six compounds. Chromatographic separation was obtained on Waters BEH RP18 column (2.1 mm × 100 mm, 2.5 μm) with the mobile phase composed of 0.1 % formic acid in acetonitrile and water, respectively. The column temperature was 35 ℃ at a flow rate of 0.4 mL min −1 . Multiple reaction monitoring was conducted in both positive and negative modes for quantitative analysis. The method was then successfully used for the determination of six compounds in EK and VEK. In addition, 1 , 2 , 4 , and 5 had evident cardiotoxicity, intestinal irritation and nutrient absorption disorders on zebrafish larvae, while no in-vivo toxicity was seen for groups given 3 and 6 (LC 50 > 200 μM). Meanwhile, 1 , 2 , 4 , 5 , and 6 significantly increased the expression of AQP3 protein ( p < 0.05) to promote the excretion of water in the colon. This study demonstrated that toxic ingenane-type diterpenoids converted into the less toxic compounds with the same core structure through the breakage of multiple ester bonds in the side chain. At the same time, the laxative effect was retained, providing useful information for the optimization of the process of EK and quality evaluation of other similar toxic Chinese herbal medicines.
研究领域:
药理学
·
毒理学
·
分析化学
·
药学
✓ 已验证
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）