Drug Research
·
2020
·Vol. 70
·期 11
·528-540
·
IF 0
Yuxin Zhang,Yihua Lu,Lijuan Wang,Yuan Tian,Zunjian Zhang
Loratadine (LOR) and its major metabolite, desloratadine (DL) are new-generation antihistamines. The hydroxylated metabolites of them, 6-OH-DL, 5-OH-DL and 3-OH-DL are also active because of their ability to inhibit binding of pyrilamine to brain H1 receptors and a tendency for distributing to specific immune-regulatory tissues. In this study, a new validated LC-MS/MS method to simultaneously quantify LOR, DL, 6-OH-DL, 5-OH-DL and 3-OH-DL in plasma and tissues was established and applied to an investigation of their pharmacokinetics and target-tissue distribution tendency for the first time. Pharmacokinetics parameters in rat were measured and the results suggest that the body’s exposure to active metabolites were much higher than to the prodrug with LOR, but much lower with DL. The tissue distribution study shows that LOR, DL and their active metabolites were widely distributed in the liver, spleen, thymus, heart, adrenal glands and pituitary gland. For immune-regulatory tissues, the concentrations of LOR, DL and their active metabolites in the spleen were much higher than in the thymus, which is related to the spleen, one of the sites where immune responses occur. LOR and its metabolites might inhibit immune-mediated allergic inflammation through the hypothalamic-pituitary-adrenal (HPA) axis. It was also found that the concentration of LOR in the heart was highest after liver and adrenal glands while those of DL, 6-OH-DL and 5-OH-DL in the liver, adrenal glands and spleen were all higher than those in the heart, which suggests that LOR may have a greater tendency to distribute in the heart than its metabolites.
✓ 已验证
产品关联
DOI
PubMed
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-8
·
IF 3.998
Zhang Youyou,Liu Liang,Ren Liang
A rapid, sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination and quantification of cantharidin in rats liver and kidney. After grinding with methanol, the supernatant was determined by LC-MS/MS using an Thermo Accucore C18 column (100 mm×2.1 mm, 2.6 μm) with a gradient elution of 0.1% formic acid and 0.1% acetonitrile, and in the subsequent analysis using selected reaction monitoring mode, three ion transitions were monitored for analyte. The limit of detection (LOD) was 0.741 ng/ml and the limit of quantitation (LOQ) was 2.471 ng/ml. Good linearity (R 2 = 0.9998) was observed for the analyte over the linear range (5–400 ng/ml). The LC-MS/MS method was applied to the analysis of rats liver and kidney in different postmortem intervals (6 h, 12 h, 24 h, 48 h, 72 h and 168 h after death) after a single dose (4 mg/kg) of cantharidin administration by gavage. At 72 h after death, the cantharidin concentration in livers and kidneys were significantly higher than that in other postmortem intervals. Linear regression equations between postmortem interval and lg postmortem cantharidin concentration in rats liver and kidney were Y = 0.007455*X + 1.332(R 2 = 0.863) and Y = 0.002689*X + 1.433 (R 2 = 0.115) respectively. The animal experiment demonstrated LC-MS/MS method can be used to determine the postmortem cantharidin concentration in rats liver and kidney and the determination of cantharidin in the rats liver after death has potential value for postmortem interval estimation in cantharidin poisoning.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Chuan-hai Tu,Xue-er Qi,Shan-shan Shui,Hui-min Lin,Soottawat Benjakul,Bin Zhang
The oxidative effects of hydroxyl radical on the alterations of lipid profiles were investigated in shrimp muscle. Chemical results indicate peroxide value (PV) and thiobarbituric acid index (TBA-i) value in oxidation-treated shrimp significantly increased with oxidation time, and hydroxyl radical concentration increased, compared with those of in fresh samples. It was assumed that radical attack might induce lipid decomposition, backbone cleavage, and/or side-chain modifications. LC/MS-based lipidomics analysis revealed 835 lipids in shrimp assigned to 27 lipid classes, including 219 PCs and 98 CLs. In total, 86 and 34 differentially abundant lipids (DALs) accumulated at lower and higher levels, respectively, were identified in OS, compared with that in FS. This indicates hydroxyl radical attack altered the lipidomics profiles of shrimp muscle to a large extent. Furthermore, DALs, including CL 62:2, PC 38:3, and PE 34:9, could be considered as promising biomarkers to distinguish fresh and oxidation-treated shrimp products.
✓ 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
Qiong Lou,Jun Wen,Yuanying Jiang,Jinghua Huang,Guorong Fan,Fenyun Song
A reliable liquid chromatography/tandem mass (LC-MS/MS) method was developed for quantitation of 3′, 4′-dimethoxy flavonol-3-β- d -glucopyranoside (DF3G) in rat plasma using pantoprazole as the internal standard. An Agilent C18 column (100 mm × 3 mm, 3.5 μm) was performed for chromatographic separation with the mobile phase composed of methanol-water (containing formic acid) at a flow rate of 0.4 mL/min. A triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source in positive ion mode was applied to quantitative analysis by multiple reacting monitoring (MRM). The MRM precursor-product ion transition of DF3G and Pantoprazole (IS) were m / z 461.1 → 299.2 and 383.9 → 200.2, respectively. Calibration curves were recovered in a concentration range of 1–500 ng/mL for plasma with a limit of lower quantification (LLOQ) of 1 ng/mL. The intra-day and inter-day precision were not >10%. The accuracy of DF3G ranged from −10% to 0.53% in quality control (QC) samples at three concentrations. DF3G was not degraded during the analysis and the storage period. All the data were validated in accordance with the FDA bioanalytical method validation guideline. The LC-MS/MS method was successfully employed in the pharmacokinetic study of the DF3G after oral administration and intravenous injection in rats.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD AND DRUG ANALYSIS
·
2018
·
IF 2.852
Xiujuan Chen,Chen Liang,Lijun Cui,Jian Le,Zheyuan Qian,Runsheng Zhang,Zhanying Hong,Yifeng Chai
Combinations of new antidepressants like duloxetine and second-generation antipsychotics like quetiapine are used in clinical treatment of major depressive disorder, as well as in forensic toxicology scenarios. The drug–drug interaction (DDI) between quetiapine and duloxetine is worthy of attention to avoid unnecessary adverse effects. However, no pharmacokinetic DDI studies of quetiapine and duloxetine have been reported. In the present study, a rapid and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of quetiapine and duloxetine in rat plasma. A one-step protein precipitation with acetonitrile was applied for sample preparation. The analytes were eluted on an Eclipse XDB-C 18 column using the mixture of acetonitrile and 2 mM ammonium formate containing 0.1% formic acid at a gradient elution within 6.0 min. Quantification was performed in multiple-reaction-monitoring mode with the ion transitions m/z 384.4 → 253.2 for quetiapine, m/z 298.1 → 154.1 for duloxetine and m/z 376.2 → 165.2 for IS (haloperidol), respectively. Good linearity was obtained in the range of 0.50–100 ng/mL for quetiapine (r 2 = 0.9972) and 1.00–200 ng/mL for duloxetine (r 2 = 0.9982) using 50 μL of rat plasma, respectively. The method was fully validated with accuracy, precision, matrix effects, recovery and stability. The validated data have met the acceptance criteria in FDA guideline. The method was applied to a pharmacokinetic interaction study and the results indicated that quetiapine had significant effect on the enhanced plasma exposure of duloxetine in rats under combination use. This study could be readily applied in therapeutic drug monitoring of major depressive disorder patients receiving such drug combinations.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2018
·Vol. 32
·期 6
·e4192
·
IF 1.688
Dan Li,Gang Zhao,Weipeng Ai,Gao Li,Luqin Si,Jiangeng Huang,Yunzhou Chen,Sanlan Wu
In this study, a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the anticancer drugs etoposide and paclitaxel in mouse plasma and tissues including liver, kidney, lung, heart, spleen and brain. The analytes were extracted from the matrices of interest by liquid–liquid extraction using methyl tert -butyl ether–dichloromethane (1:1, v/v). Chromatographic separation was achieved on an Ultimate XB-C 18 column (100 × 2.1 mm, 3 μm) at 40°C and the total run time was 4 min under a gradient elution. Ionization was conducted using electrospray ionization in the positive mode. Stable isotope etoposide-d3 and docetaxel were used as the internal standards. The lower limit of quantitation (LLOQ) of etoposide was 1 ng/g tissue for all tissues and 0.5 ng/mL for plasma. The LLOQ of paclitaxel was 0.4 ng/g tissue and 0.2 ng/mL for all tissues and plasma, respectively. The coefficients of correlation for all of the analytes in the tissues and plasma were >0.99. Both intra- and inter-day accuracy and precision were satisfactory. This method was successfully applied to measure plasma and tissue drug concentrations in mice treated with etoposide and paclitaxel-loaded self-microemulsifying drug-delivery systems.
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Yu Yang,Xingyan Bao,Jiangyue Ning,Ruiyan Huang,Yuan Liang,Zelong Yan,Haotian Chen,Li Ding,Chang Shu
The investigation of peptide drugs has become essential in the development of innovative medications for hypertension. In this study, a sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the plasma concentration and stability of the antihypertensive peptide FR-6 in rats. An isotopically labeled peptide (with an unchanged sequence) was utilized as an internal standard (IS) for validation purposes. Subsequently, this assay was employed to examine the pharmacokinetics of different administration methods (tail vein and gavage) in Sprague Dawley (SD) rats. Extracted plasma samples underwent sample preparation through methanol protein precipitation, followed by elution of FR-6 on Wondasil C18 Superb column (4.6 × 150 mm, 5 μm), using a mobile phase consisting of formic acid (0.1%) in water (A) and formic acid (0.125%)-ammonium formate (2 mM) in methanol (B). Ion pairs corresponding to FR-6 and IS were monitored via multiple reaction monitoring (MRM) under positive ion mode: m / z 400.7 → 285.1 for FR-6 and m / z 406.1 → 295.1 for IS detection respectively. The method exhibited excellent linearity with respect to FR-6 concentrations. In addition, the inter-day and intra-day precision were 0.61–6.85% and 1.76–11.75%; the inter-day and intra-day accuracy were −7.28–0.13% and −7.20–2.28%, respectively. In conclusion, the matrix effect, extraction recovery, and stability data were validated according to FDA recommended acceptance criteria for bioanalytical methods. This validated method serves as a reliable tool for determining the concentration of antihypertensive peptide FR-6, and has been successfully applied in pharmacokinetic studies involving rats.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHROMATOGRAPHIA
·
2025
·
IF 1.3
Jiang Qiaoling,Wu Qiaoli,Chen Shuhang,Zeng Tianfu,Tong Xiaoyi
This study introduces a rapid LC–MS/MS method designed to simultaneously quantify 14 water-soluble vitamins and their metabolites in human serum. The protein precipitation with metaphosphoric acid and stable isotope dilution techniques are utilized in this method. An Agilent XDB C18 column and dynamic ionization mode switching are adopted, enabling the completion of a single sample analysis within 5 min. The method has undergone rigorous validation. The lower limits of quantification (LLOQs) range from 0.3 to 400 ng/mL, with recovery rates between 80 and 120%. Intra-day and inter-day relative standard deviations (RSDs) are below 15%. The matrix effects are controlled within ± 15%, and the analyte carryover is less than 20% of the LLOQ. The stability tests have demonstrated that samples remain stable at room temperature (25 °C) for 10 h, at − 20 °C for 7 days, and can withstand one freeze–thaw cycle. Extracted samples are stable in the autosampler (4 °C) for 24 h. The method was applied to serum samples from 150 healthy individuals. Non-parametric statistical analysis was carried out to establish clinical reference intervals, which provides valuable data for the clinical evaluation of vitamin and metabolite levels in serum.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Fangbo Xia,Peng Cui,Ling Liu,Junhe Chen,Qiqi Zhou,Qian Wang,Hongwei Zhou
The gut microbiome plays pivotal roles in various physiological and pathological processes, with key metabolites including short chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (TRP) derivatives gaining significant attention for their diverse physiological roles. However, quantifying these metabolites presents challenges due to structural similarity, low abundance, and inherent technical limitations in traditional detection methods. In this study, we developed a precise and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method utilizing a chemical isotope derivatization technique employing 4-(aminomethyl)-N,N-dimethylaniline- d 0 / d 6 (4-AND- d 0 / d 6 ) reagents to quantify 37 typical gut microbiome-derived metabolites. This method achieved an impressive 1500-fold enhancement in sensitivity for detecting metabolites, compared to methods using non-derivatized, intact molecules. Moreover, the quantitative accuracy of our chemical isotope derivatization strategy proved comparable to the stable isotope labeled internal standards (SIL-IS) method. Subsequently, we successfully applied this newly developed method to quantify target metabolites in plasma, brain, and fecal samples obtained from a neonatal hypoxic-ischemic encephalopathy (HIE) rat model. The aim was to identify crucial metabolites associated with the progression of HIE. Overall, our sensitive and reliable quantification method holds promise in elucidating the role of gut microbiome metabolites in the pathogenesis of various diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2025
·
IF 2.6
Aiwen Shi,Bin Qi,Xiaolei Tang,Li Liu,Chang Wang,Ziyi Jia
Frankincense is a resin drug widely used in the medical field. Comprehensive qualitative and quantitative analysis of the differences in the chemical composition of frankincense, stir fried frankincense and vinegar frankincense by combined GC-MS and LC-MS chromatographic methods. In GC-MS analysis, six chemical compositions with high content in frankincense were selected, including β-ocimene、1-octanol、acetic acid, octyl ester、nerolidol、lauric acid and incensole acetate. In the LC-MS analysis, eight more widely studied chemical compositions were selected, including 11-keto-β-boswellic acid、β-elemolic acid、acetyl-11-keto-β-boswellic acid、β-elemonic acid、α-boswellic acid、β-boswellic acid、3-0-acetyl-α-boswellic acid、3-0-acetyl-β-boswellic acid. In addition, some chemical composition of frankincense were identified by LC-MS fragmentation information.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Lu Zhang,Ling-Ling Wang,Hao Zeng,Bin Li,Hua Yang,Guang-Ji Wang,Ping Li
Background Mild and systematically improving multiple metabolic disorders was a focused view for Compound Danshen Dripping Pills playing synergistic effects through multiple components and multiple targets. The difference in overall therapeutic effects and endogenous metabolic regulation between short- and long-term administration was still unclear. Purpose This study aimed to explore the difference in endogenous metabolic regulation between short- and long-term Compound Danshen Dripping Pills (CDDP) administration against acute myocardial infarction (AMI). Methods The model of AMI was induced by ligating the left anterior descending coronary artery . The cardiac protection effects of CDDP were investigated by echocardiography , 1- or 2-week were defined as short- and long-term based on desirable efficacy variability. The entire metabolic changes between short- and long-term administration of CDDP were profiled by UPLC-Q-TOF-MS. In addition, the metabolic regulatory network of CDDP administration against myocardial infarction rats was also compared with those of a typical chemical drug isosorbide 5-mononitrate (ISMN). Results After 1- or 2-week continuous oral administration , CDDP could significantly alleviate AMI-induced cardiac dysfunction. By using LC-MS-based metabolomics analyses, we systematically investigated the metabolic profiles of plasma and heart tissue samples at fixed exposure time-points (2 h, 24 h) from AMI rats with CDDP treatment . Most interestingly, global endogenous metabolic changes were observed in cardiac samples collected at different stages post consecutive CDDP administration, fluctuating at 2 and 24 h after 1 week but stabilizing after 2 weeks. The disrupted metabolic pathways such as glycerophospholipid , amino acids , fatty acids, and arachidonic acid metabolism were reconstructed after both short- and long-term CDDP treatment, while taurine and hypotaurine metabolism and purine metabolism contributed to the whole efficacy after long-term CDDP administration. Conclusion Long-term CDDP treatment plays prolonged and stable efficacy against AMI compared with short-term treatment by specifically regulating purine and taurine and hypotaurine metabolism and systematically redressing metabolic disorders.
研究领域:
药理学
·
心脏病学
·
代谢组学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
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
危险品化学品经营许可证（带存储）