JOURNAL OF CHROMATOGRAPHIC SCIENCE
·
2019
·Vol. 58
·期 1
·31-36
·
IF 1.216
Zhou Li,Xi Wang,Zhang Hui,Sun Lili,Yu Jinlong,Zou Qiaogen
A simple and enantioselective method was developed and validated for the simultaneous determination of (R)- and (S)-trelagliptin in beagle dog plasma by chiral liquid chromatography tandem mass spectrometry. Trelagliptin enantiomers and (R)-rabeprazole (as internal standard, IS) were extracted from plasma samples by liquid–liquid extraction and separated on a CHIRALCEL OX-3R column using acetonitrile-5 ammonium bicarbonate as the mobile phase in gradient elution mode. The multiple reactions monitoring transitions of m/z 358.1→341.2 and 359.9→150.1 were used to quantify trelagliptin enantiomers and IS, respectively. This method was validated for sensitivity, specificity, linearity, precision, accuracy and stability of specific analytes under various conditions. And it was successfully applied to evaluating the pharmacokinetic profile of trelagliptin enantiomers in beagle dogs after single intravenous administration of (R)-trelagliptin injection (at 1 mg/kg) and oral administration (at 6.7 mg/kg). In this study, no chiral bioconversion of (R)-trelagliptin to (S)-trelagliptin in beagle dog plasma was observed. The absolute bioavailability of (R)-trelagliptin was identified to be 128.2%.
研究领域:
药物分析
·
药理学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2014
·Vol. 28
·期 12
·1738-1743
·
IF 1.662
Ling-ling Zeng,Li-li Sun,Qiaogen Zou,Fan Zhou,Ping Wei,Ping-kai Ouyang
Vilazodone hydrochloride (CAS 163521-12-8) is polymorphic and has 15 crystal forms, referred to as I–XI and XIII–XVI. In the study, we prepared and performed structural identification of a new crystal form named XVII. To investigate this in vivo , a rapid and sensitive method based on liquid–liquid extraction, followed by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) was developed and validated for the determination of vilazodone hydrochloride in dog plasma. This HPLC-MS/MS method was successfully applied to a bioavailability comparison of two crystal forms of vilazodone hydrochloride (IV and XVII) in six healthy beagles using a single-dose, two-way crossover design. The maximum plasma concentration ( C max ), the time taken to reach C max , and the area under the concentration–time curve were determined following oral administration of 10 mg vilazodone hydrochloride (IV or XVII) to beagles. These analyses revealed no significant bioavailability differences between vilazodone hydrochloride forms IV and XVII in dogs. Copyright © 2014 John Wiley & Sons, Ltd.
研究领域:
药学
·
分析化学
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DOI
PubMed
高影响因子
Analytical Methods
·
2016
·Vol. 8
·期 6
·1405-1414
·
IF 1.915
Na Cao,Lei Liu,Yuan-bin Hao,Li-li Sun,Qiao-gen Zou,Xing-ling Ma,Kai-he Xiong
A sensitive, rapid and stable HPLC-MS/MS method has been developed and validated for the determination of rabeprazole enantiomers and their four metabolites, namely rabeprazole thioether, rabeprazole sulfone and desmethyl rabeprazole enantiomers, in beagle dog plasma using esomeprazole as the internal standard. The analytes and the internal standard were extracted from plasma samples by liquid–liquid extraction and separated on a Chiral-HSA column using acetonitrile-10 mmol L−1 ammonium acetate as the mobile phase by gradient elution. The method was validated with respect to sensitivity, specificity, linearity, precision, accuracy and especially the stability of analytes under various conditions, and was successfully applied in evaluating the pharmacokinetic profiles of racemic rabeprazole, the pure enantiomers and their metabolites in beagle dogs after single intravenous administration of (R)-rabeprazole sodium injection (at 0.33, 1 and 3 mg kg−1), (S)-rabeprazole sodium injection (at 1 mg kg−1) and racemic rabeprazole sodium injection (at 2 mg kg−1). The two enantiomers showed different profiles of pharmacokinetic parameters. The AUC0–t and t1/2 values of (R)-rabeprazole were higher and the clearance (CL) value of (R)-rabeprazole was lower than that of (S)-rabeprazole. Compared to (S)-rabeprazole, the higher absorption and slower elimination of (R)-rabeprazole explain why (R)-rabeprazole is more effective than the racemate.
研究领域:
药物分析
·
药理学
·
临床医学
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产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHIC SCIENCE
·
2023
·
IF 1.3
Chen Yuyang,Huang Xiaofang,Guo Zizheng,Zhang Jingyu,Zhang Lixin,Dai Renke
Ivermectin has been widely used for antiparasitic drug, and has recently shown a broad-spectrum antiviral activity, including anti-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacokinetic property of ivermectin has not been fully investigated yet. During the plasma preparation, ~32–46% of ivermectin was found in the precipitation. An Liquid Chromatograph-Mass Spectrometer (LC–MS/MS) method for ivermectin in the whole blood samples from beagle dogs was developed and validated. The specificity, accuracy, precision (intra-day and inter-day), matrix effect, recovery and stability of analyte reported here are satisfied with the criteria of Food and Drug Administration (FDA)-Bioanalysis guideline. The oral administrations pharmacokinetics of ivermectin in beagle dogs under fasting and after high-fat meal were studied, and the following parameters were obtained: fasting Cmax, 104 ± 35 μg·L−1; area under the concentration–time curve (AUC0–∞), 2,555 ± 941 h·μg·L−1; and high-fat meal Cmax, 147 ± 35 μg·L−1; AUC0–∞, 4,198 ± 1,279 h·μg·L−1. When the P-gp inhibitor curcumin was also coadministrated orally, Cmax and AUC0–∞ were found to be 177 ± 57 and 4,213 ± 948 h·μg·L−1, respectively. With the comparison to fasting treatment, coadministration of P-gp inhibitor curcumin resulted in increase of the exposure of ivermectin by 1.6-fold, while the exposure after the high-fat diet versus fasting was increased approximately in 1.4-fold, indicating that alternative absorption might play an important role for increasing the exposure of ivermectin for future clinic applications.
研究领域:
药理学
·
兽医学
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临床医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2020
·Vol. 43
·期 12
·2290-2300
·
IF 2.878
Guanghui Ren,Huili Chen,Mei Zhang,Nan Yang,Hui Yang,Chuanru Xu,Jiaming Li,Chen Ning,Zhongjin Song,Shiyu Zhou,Siliang Zhang,Xiaoqian Wang,Yang Lu,Ning Li,Yongjie Zhang,Xijing Chen,Di Zhao
Oroxylin A, obtained from the root of Scutellaria baicalensis Georgi , is a flavonoid with antitumor and other pharmacological activities. Our previous studies showed for the first time that it is mainly metabolized to oroxylin A sodium sulfonate by sulfotransferase enzymes in beagle dogs. In this study, rapid, universal, selective, and robust ultra-high-performance liquid chromatography–tandem mass spectrometry methods were established and fully validated to quantitatively detect oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in beagle dog plasma. The quantitative analysis for oroxylin A sodium sulfonate was reported for the first time. Plasma samples were processed with acetonitrile, a universal protein precipitant. Gradient elution was performed to resolve carryover effects and to achieve separation efficiency and sufficient chromatographic retention. The linear relationships of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in plasma were in the range of 2.0–500.0, 5.0–500.0, and 1.881–940.5 ng/mL, respectively. The assay method was successfully applied to pharmacokinetic study. This is the first paper that reveals the pharmacokinetic profile of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate after single-dose intravenous and oral administration of Oroxylin A in beagle dogs.
研究领域:
药物分析
·
药理学
·
代谢组学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2024
·Vol. 17
·期 1
·141
·
IF 4.3
Jiahui Zhang,Junxiang Wang,Lingfan Chen,Xiangbin Yu,Shuihua Zhang,Yue Yu
Levamisole (LVM) is considered an immunomodulatory agent that has the potential to treat various cancer and inflammation diseases. However, there is still much debate surrounding the toxicokinetic and toxicological information of LVM. Therefore, it is crucial to assess its toxicity to provide useful data for future human LVM risk assessments. In this study, a barrier environment was established under the guidance of good laboratory practice (GLP) at the Fujian Center for New Drug Safety Evaluation. Male beagle dogs were orally administered with 5, 15, and 30 mg/kg of LVM daily for four weeks. Toxicity assessment was based on various factors such as mortality, clinical signs, food and water consumption, body weight, body temperature, electrocardiogram, ophthalmological examination, hematology, serum biochemistry, organ/body coefficients, histopathological study, and toxicokinetic analysis. The results of this study showed that LVM did not exhibit any significant toxicological effects on beagle dogs at the exposure levels tested. A no observed adverse effect level (NOAEL) of LVM was set at 30 mg/kg/day for male beagle dogs, which is equivalent to a 12-fold clinical dose in humans. Moreover, the repeated exposure to LVM for four weeks did not lead to any bioaccumulation. These findings provide valuable insights for future human LVM risk assessments.Keywords:levamisole;repeated dose toxicity;toxicokinetics;NOAEL;beagle dogs
研究领域:
药理学
·
毒理学
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DOI
PubMed
高影响因子
MOLECULES
·
2015
·Vol. 20
·期 11
·20031-20041
·
IF 2.416
Jie Zhao,Ting Geng,Qi Wang,Haihong Si,Xiaoping Sun,Qingming Guo,Yanjing Li,Wenzhe Huang,Gang Ding,Wei Xiao
Ginkgolide B (GB), an important active constituent ofGinkgo bilobaextract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18column (1.8 μm, 2.1 × 50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions atm/z(Q1/Q3) 423.1/367.1 for GB andm/z269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2–200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within ±12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The Cmaxvalues of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations.Keywords:ginkgolide B;hot-melt extrusion;liquid layer;beagle dog plasma;pharmacokinetics;LC-MS/MS
研究领域:
药理学
·
药物分析
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Meng Jiacheng,Qiu Chenxu,Lu Chenyue,He Xin,Zhao Xinghua
To overcome the poor solubility, permeability, and bioavailability of the plant isoflavone daidzein (DAI), a novel salt of DAI with anhydrous piperazine (PIP) was obtained based on cocrystallization strategy. The new salt DAI-PIP was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, and optical microscopy. The results showed that the maximum apparent solubility (Smax) of DAI-PIP increased by 7.27-fold and 1000-fold compared to DAI in pH 6.8 buffer and water, respectively. The peak apparent permeability coefficient (Papp) of DAI-PIP in the Caco-2 cell model was 30.57 ± 1.08 × 10−6 cm/s, which was 34.08% higher than that of DAI. Additionally, compared to DAI, the maximum plasma concentration (Cmax) value of DAI-PIP in beagle dogs was approximately 4.3 times higher, and the area under the concentration-time curve (AUC0-24) was approximately 2.4 times higher. This study provides a new strategy to enhance the dissolution performance and bioavailability of flavonoid drugs, laying a foundation for expanding their clinical applications.
研究领域:
药学
·
药物递送
·
药理学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 9
·期 9
·2200-2211
·
IF 5.344
Qing Sun,Mengting Duan,Wei Fan,Bing Fan
Enterococcus faecalis is the main cause of refractory root canal infections in human teeth. The control of root canal infection is one of the conditions necessary for the successful treatment of refractory root canal infections. In the present study, nano-scale silver–zinc–calcium–silica particles loaded with different ratios of silver–zinc were successfully prepared (Ag0.5Zn3-MCSNs and Ag0.5Zn10-MCSNs). The release profiles, antibacterial activity against E. faecalis, infiltration depth into dentinal tubules, biocompatibility and effects on dentin microhardness in vitro were investigated. In addition, the antimicrobial effects of the particles against Enterococcus faecalis reinfection were evaluated in vivo in the teeth of beagle dogs. Ag, Zn, Ca and Si were released from Ag–Zn-MCSNs, and the atomic ratio of silver and zinc released can reach the optimal value of 1 : 12 (Ag0.5Zn10-MCSNs). The particles also showed good biocompatibility and antibacterial activity against Enterococcus faecalis and did not reduce the hardness of dentin. The nanoparticles could be driven into the dentinal tubules of dentin slices by ultrasonic activation. In the root canals of beagle dogs, both Ag0.5Zn3-MCSNs and Ag0.5Zn10-MCSNs demonstrated strong preventive effects against E. faecalis infection. The Ag–Zn–Ca–Si mesoporous nanoparticles may develop into a new effective root canal disinfectant or root canal sealer.
研究领域:
牙科学
·
纳米技术
·
材料科学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Tao Ke,Zhongyuan Zhao,Junhuan Lin,Fengting Ou,Kaikai Chen,Kui Zeng,Debo He,Shengqiang Tong,Xinyi Wang,Lushan Yu,Jing Chen
The aim of this study was to develop and fully validate a sensitive and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantification of pristinamycin ⅠA (PⅠA) and pristinamycin ⅡA (PⅡA) in plasma of beagle dogs after oral administration of pristinamycin tablets. PⅠA, PⅡA and quinupristin (internal standard, IS) were separated on an Agilent Eclipse Plus C 18 column (2.1 mm × 100 mm, 3.5 μm particle size) by using gradient elution consisting of methanol and water (0.1 % formic acid) at a flow rate of 0.4 mL/min in 4.0 min. Multiple reaction monitoring (MRM) mode was performed to quantify data under monitoring precursor-product ion transitions of m/z 867.6→134.1, 548.4→287.1 and 1022.7→133.9 for PⅠA, PⅡA and IS at positive ion mode, respectively. The method was developed at linearity ranging from 1.0 to 1000 ng/mL for all analytes.The accuracy of PⅠA and PⅡA was observed to range between −10.6 % and 7.1 %, while the precision was found to be within 8.9 %. No significant matrix effect was observed. PⅠA and PⅡA demonstrated stability during sample storage, preparation and analytic procedures. Furthermore, this method was successfully applied in the investigation of the pharmacokinetic profile of PⅠA and PⅡA in beagle dogs after oral administration of pristinamycin tablets (75 mg for PⅠA and 175 mg for PⅡA). The biological half-life (t 1/2 ) was determined to be 1.75 ± 0.07 h and 1.44 ± 0.31 h for PⅠA and PⅡA, respectively. The areas under curves (AUC 0-t ) of PⅠA and PⅡA were 80.7 ± 24.6 and 230 ± 94.8 μg/L·h, respectively.
研究领域:
分析化学
·
药理学
·
兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Yilin Wang,Shanshan Wang,Xueqin He,Yupei Li,Tao Xu,Lin Xu,Bo Yang,Xinnian Fan,Weifeng Zhao,Changsheng Zhao
The development of wearable artificial livers was restricted to device miniaturization and bleeding risk with water-soluble anticoagulants. Herein, a double-deck column filled with solid anticoagulant microspheres and Kevlar porous microspheres (KPMs, bilirubin adsorbents) was connected with the principle machine of wearable artificial liver (approximately 9 kg) to treat hyperbilirubinemia beagles for the first time. With the initial normal dose of heparin, the double-deck column could afford 3 h hemoperfusion in whole blood without thrombus formation. The removal efficiency of the double-deck column for total bilirubin (TBIL) was 31.4%. Interestingly, the excessive amounts of hepatocyte metabolites were also decreased by approximately 25%. The “anticoagulant + column” realized safe and effective whole blood hemoperfusion without the plasma separation system and heparin pump; however, the proposed principle machine of wearable artificial liver and “anticoagulant + column” cannot completely replace the bio-liver now. The intelligence of the device and the versatility of the adsorbent need to be improved; moreover, advanced experimental techniques need to be developed to validate the survival rates in animals. Overall, this study is a meaningful trial for the development of wearable artificial livers in the future.
研究领域:
生物医学工程
·
肝病学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Zhao Mengdi,Zhang Yuanyuan,Li Yueyao,Liu Keyuan,Bao Kun,Li Guangyu
There is growing interest in the potential health benefits of probiotics for both humans and animals. The study aimed to investigate the effects of feeding the canine-derived probiotic Pediococcus acidilactici GLP06 to adult beagles by analysing the microbiome and metabolome. Twenty-four healthy adult beagles were randomly assigned to four groups. The CK group received a standard diet, while the three probiotic groups, the LG group (2 × 108 CFU/day/dog), MG group (2 × 109 CFU/day/dog), and HG group (2 × 1010 CFU/day/dog), received the standard diet supplemented with varying amounts of probiotics. The results show that, compared to the CK group, total antioxidant capacity was significantly increased in the MG and HG groups (p < 0.05), and superoxide dismutase and catalase were significantly increased in the HG group (p < 0.05). Compared to the CK group, malondialdehyde and blood urea nitrogen content were significantly decreased in the MG and HG groups (p < 0.05). Additionally, secretory immunoglobulin A activity was significantly increased in the HG group compared to the CK and LG groups (p < 0.05), and immunoglobulin G activity was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). In addition, compared with the CK group, the abundance of Faecalitalea and Collinsella increased in the LG group, and the relative abundance of Tyzzerella and Parasutterella increased in the MG group. The α diversity and the relative abundances of beneficial bacteria (Faecalibacterium, Lachnospiraceae_NK4A1316, and Ruminococcaceae_UCG-005) were higher in the HG group than in the CK group. Furthermore, acetic acid content was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). Butyric acid, isobutyric acid, and the total SCFA content were significantly increased in the HG group compared to the CK group (p < 0.05). Moreover, metabolome analysis revealed 111 upregulated and 171 downregulated metabolites in the HG group. In conclusion, this study presents evidence that supplementing with P. acidilactici GLP06 can have a positive impact on antioxidant activity, immunoproteins, SCFAs, and gut microbiota in adult beagles. These findings highlight the potential of probiotics as a dietary intervention to enhance gut health and overall wellbeing in companion animals.
研究领域:
兽医学
·
微生物学
·
营养学
·
免疫学
·
代谢组学
✓ 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）