MOLECULES
·
2023
·Vol. 28
·期 5
·2416
·
IF 4.6
Junchen Liu,Yuehang Wu,Wenrui Ma,Hongyan Zhang,Xianyao Meng,Huirong Zhang,Miaomiao Guo,Xiao Ling,Li Li
Panax notoginseng(Burk) F. H. Chen is a traditional Chinese medicinal and edible plant. However,Panax notoginsengflower (PNF) is rarely used. Therefore, the purpose of this study was to explore the main saponins and the anti-inflammatory bioactivity of PNF saponins (PNFS). We explored the regulation of cyclooxygenase 2 (COX–2), a key mediator of inflammatory pathways, in human keratinocyte cells treated with PNFS. A cell model of UVB-irradiation-induced inflammation was established to determine the influence of PNFS on inflammatory factors and their relationship with LL–37 expression. An enzyme-linked immunosorbent assay and Western blotting analysis were used to detect the production of inflammatory factors and LL37. Finally, liquid chromatography–tandem mass spectrometry was employed to quantify the main active components (ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, and notoginsenoside R1) in PNF. The results show that PNFS substantially inhibited COX–2 activity and downregulated the production of inflammatory factors, indicating that they can be used to reduce skin inflammation. PNFS also increased the expression of LL-37. The contents of ginsenosides Rb1, Rb2, Rb3, Rc, and Rd in PNF were much higher than those of Rg1, and notoginsenoside R1. This paper provides data in support of the application of PNF in cosmetics.Keywords:Panax notoginsengflower;UVB;inflammatory factor;antibacterial peptide LL-37;total saponin;LC/MS/MS
研究领域:
药理学
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生物化学
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药物化学
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化妆品
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DOI
PubMed
高影响因子
Bioanalysis
·
2022
·Vol. 14
·期 7
·
IF 2.695
Xueyuan Zhang,Yuhuan Ji,Jinzhi Liu,Ji Liu,Chunlei Li,Laixin Wang,Min Meng,Limei Zhao
Background: Because of the delicate nature of liposomes, bioanalysis of free and liposomal-encapsulated drugs is among the most challenging assays to perform. Current regulatory guidance for bioanalysis is not sufficient to address the complexity of this particular formulation. Method & results: Three individual LC–MS/MS methods to quantify free amphotericin B (10–3000 ng/ml) and encapsulated amphotericin B (100–50,000 ng/ml) in pretreated human plasma and total amphotericin B (100–50,000 ng/ml) in human plasma were fully validated and applied to a bioequivalence study. The acceptance criteria and experimental design of additional validation tests using cross quality control were carefully deliberated a priori and included in the sample analysis as well. Discussion: Additional validation tests are necessary to demonstrate that the measured concentration of the intended component is accurate and free of interference from other coexisting components in the sample. These practices can be used as guidance for future liposomal drug method validation.
研究领域:
药理学
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分析化学
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临床医学
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DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2023
·Vol. 415
·期 25
·6345-6353
·
IF 4.3
Wang Aimin,Fan Yuting,Fu Jun,Song Fengrui,Liu Zhiqiang,Liu Shu
Metabolomics is a biochemical analysis tool for identifying metabolic phenotypes and used to reveal the pathogenic mechanisms of disease and to inform drug-targeted therapies. Carboxyl-containing metabolites (CCMs) account for an important proportion of the metabolome, but because of the diversity of physical and chemical properties of CCMs in biological samples, traditional liquid chromatography–mass spectrometry (LC-MS) targeted metabolome analysis methods cannot achieve simultaneous quantification of multiple types of CCMs. Therefore, we proposed for the first time a targeted metabolomics strategy using isoniazid derivatization combined with LC-MS/MS to simultaneously quantify 39 CCMs of 5 different types (short-chain fatty acids, amino acids, bile acids, phenylalanine and tryptophan metabolic pathway acids) with large polarity differences associated with Alzheimer’s disease (AD) and significantly improve the detection coverage and sensitivity. The yields of isoniazid derivative CCMs were high and could guarantee the accuracy of CCM quantification. The LODs of CCMs increased significantly (1.25–2000-fold) after derivatization. The method showed good selectivity, intra-day and inter-day accuracies and precisions, and repeatability. There was no significant effect on the determination of CCMs in terms of matrix effect and recovery. CCMs showed good stability. And CCMs showed good stability under short-term storage and freeze-thaw cycles. At the same time, the regulatory effects of Schisandrae chinensis Fructus and Ginseng Radix et Rhizoma (SG) herb pair on CCM metabolic disorders in feces, urine, serum, and the brain of AD rats were elucidated from the perspective of targeted metabolomics. In combination with pharmacodynamic evaluation and gut microbiota analysis, the mechanism of SG herb pair on AD rats was comprehensively understood. In summary, this innovative isoniazid derivatization combined with a targeted metabolomics method has great potential for trace biological lineage analysis. Graphical
研究领域:
代谢组学
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分析化学
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神经退行性疾病
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药理学
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中医药学
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肠道微生物
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DOI
高影响因子
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
·
2021
·Vol. 22
·期 2
·274-280
·
IF 2.837
Shixing Zhu,Jiayuan Zhang,Zhihua Lv,Mingming Yu
Background: Apigenin, a natural plant flavone, has been shown to possess a variety of biological properties. Objective: In this report, a highly selective and sensitive LC-MS/MS method was developed and validated for the determination of apigenin in rat plasma. Methods: Analysts were separated on the HSS T3 column (1.8 μm 2.1×100 mm) using acetonitrile and 0.1% formic acid in 2mM ammonium acetate buffer at a supply rate of 0.200 mL/min as eluent in gradient model. Results: Plasma samples were treated by protein precipitation using acetonitrile for the recovery ranging from 86.5% to 90.1% for apigenin. The calibration curves followed linearity in the concentration range of 0.50-500ng/mL. The inter-day and intra-day precisions at different QC levels within 13.1% and the accuracies ranged from -10.6% to 8.6%. Conclusion: The assay has been successfully applied to the pharmacokinetic study of apigenin in rats.
研究领域:
分析化学
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药理学
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生物分析
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药学
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DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2025
·
IF 4
Lei Ding,Chundan Ye,Junchen Zhu,Cuirong Sun
Chiral impurity analysis presents significant challenges due to limitations of detection methods. Levodopa (L-Dopa) is the primary medication for Parkinson's disease treatment for over 50 years. However, the detection of its chiral impurity is difficult due to the similarity of polarity. This study presents a novel analytical method for the quantitative detection of trace amount of D-Dopa, as well as other three impurities. The method demonstrated excellent chromatographic resolution for D-Dopa and L-Dopa (resolution = 4.15) and achieved a derivatization efficiency of 97% using a chlorine-labeled chiral probe (D-BPCl) for chemical derivatization, followed by analysis with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on a conventional C18 column. Meanwhile, D-BPCl showed strong chiral selectivity on D-Dopa, and the ratio of mass spectrometric response for labeled D-Dopa to that of L-enantiomers was 2.78-fold under the same condition. The developed method demonstrates high sensitivity with detection limits of 7.88 μ g L -1 for D-Dopa, and 9.85 μ g L -1 for L-Dopa, with good linearity for every analyte (R 2 > 0.99), recoveries ranging from 94.1% to 106.8%, and high repeatability with relative standard deviation (RSD) values predominantly below 5%. Then the method was applied to analyze fifteen batches of levodopa tablets from five manufacturers. D-Dopa was successfully detected with the corresponding content ranging from 0.15% to 0.44%, which suggests that D-Dopa are more likely generated during the production process. The study underscores the significant safety concerns regarding Dopa-containing medications.
研究领域:
药物分析
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药物质量控制
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手性分离
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药物代谢
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分析化学
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产品关联
DOI
PubMed
高影响因子
CLINICA CHIMICA ACTA
·
2025
·
IF 2.9
Feng Chen,Xiaoxia Yang,Yayun Tan,Huanhuan Li,Yan Yan,Xiang Zhao,Chengfeng Qiu
Pneumocystis jirovecii pneumonia (PJP) is a high-mortality fungal infectious disease, and the changes in tryptophan metabolism and its diagnostic value in PJP remain unclear. This study aimed to elucidate the specific tryptophan metabolic profile in PJP patients by establishing and validating an LC-MS/MS method for the simultaneous quantification of tryptophan and its nine key metabolites in human serum. Serum samples from 46 PJP patients, 35 pulmonary tuberculosis (PTB) patients and 40 healthy controls were analyzed. The method achieved complete chromatographic separation within 5.5 min, with an extraction recovery rate > 95.8 % and matrix effects ranging from 86.0 % to 106.8 %, meeting the comprehensive validation criteria set by FDA and EMA guidelines. PJP patients exhibited significantly higher serum levels of 3-hydroxykynurenine (3−HK) compared to the PTB and healthy control groups (26.0 vs. 11.5 vs. 8.94 ng/mL, p < 0.001), while levels of 5-hydroxytryptophan and indole-3-acetic acid were significantly lower ( p < 0.05). The 3-Hydroxyanthranilic Acid/3-hydroxykynurenine ratio was also markedly reduced in the PJP group. ROC analysis demonstrated strong diagnostic performance for PJP with 3-hydroxykynurenine (AUC = 0.919), 5-hydroxytryptophan (AUC = 0.816), indole-3-acetic acid (AUC = 0.705), and the 3-Hydroxyanthranilic Acid/3-hydroxykynurenine ratio (AUC = 0.743). The validated LC-MS/MS method is rapid, sensitive, high-throughput and enables precise analysis of tryptophan metabolism. The distinct metabolic signature—particularly elevated 3-hydroxykynurenine, reduced 5-hydroxytryptophan and indole-3-acetic acid, and an altered 3-Hydroxyanthranilic Acid/3-hydroxykynurenine ratio—provides novel biomarkers for PJP diagnosis and offers new insights into its immunometabolic mechanisms.
研究领域:
传染病学
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代谢组学
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临床化学
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免疫代谢
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分析化学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2020
·Vol. 146
·期 5
·1725-1733
·
IF 3.978
Chang Shu,Teng-Fei Li,Duo Li,Zhong-Qiu Li,Xing-Hua Xia
Protein drugs showing strong pharmaceutical activity, high specificity, and low toxicity and side effects have drawn extensive attention in the field of life sciences and medicine. Precise evaluation of the function of these drugs requires accurate and sensitive detection methods. Here, we report a novel chromatography-tandem mass spectrometry (LC-MS/MS) method for sensitive and selective detection of protein drugs. Magnetic nanoparticles (Apt29@MNPs) were functionalized by thrombin aptamers, and quantum dots (Apt15@ss@QDs) were dual-functionalized with quantitative thrombin aptamers and small molecules with high ionization efficiency as the mass barcode. After Apt29@MNPs specifically purify and enrich thrombin from biological samples, they can form a nano “sandwich structure” when Apt15@ss@QDs are added, resulting in the release of the mass barcode for LC-MS/MS analysis via the cutting of the disulfide bond. Since there is a higher quantitative molecular ratio of mass barcode to thrombin in the nano-“sandwich structure”, quantitative detection of thrombin with high sensitivity and selectivity can be achieved via the LC-MS/MS detection of the mass barcode with high ionization efficiency rather than thrombin, which effectively avoids the disadvantages of direct protein detection by mass spectrometry. The established method for thrombin detection shows a good linear relationship in a concentration range of 0.00115–1.15 nM with a limit of detection (LOD) of 0.0007 nM. The present work provides a new approach for the effective and sensitive quantitative analysis of protein drugs and would be of great significance in promoting the development of protein drugs and clinical applications.
研究领域:
分析化学
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生物化学
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药学
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临床医学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Huijie Lv,Siqi Luo,Ruochen Tian,Wenhua Zhang,Baoshan Sun,Yan Cui
Epinephrine and norepinephrine are a class of chiral endogenous catecholamines, which are known as major neurotransmitters. This work described a new LC–MS/MS method coupled with pre-column derivatization, enabling the simultaneous enantiomeric separation of epinephrine and norepinephrine in rat plasma. After protein precipitation procedure, the samples were derivatized with ( S )-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester, [( S )-NIFE]. The derivatives resolved with good baseline separation on an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with mobile phase composed of methanol with 0.2% formic acid in water at a flow rate of 0.2 mL/min. Analysis was performed by multiple reaction monitoring in positive ionization mode. The linear ranges were 1.0–500 ng/mL for epinephrine enantiomers and 1.5–750 ng/mL for norepinephrine enantiomers. The lower limits of quantification for epinephrine and norepinephrine enantiomers were 1.0 and 1.5 ng/mL, respectively. The intra-day and inter-day precision were all less than 10.7% and accuracy ranged from 96.0 to 101.5%. Recoveries for all the analytes were more than 80.3%. The proposed method was successfully applied to simultaneously determine endogenous epinephrine and norepinephrine enantiomers in rat plasma. l -epinephrine and l -norepinephrine were sensitively and accurately quantified while both the d -enantiomers were not detected. Additionally, epinephrine enantiomers were analyzed for stereoselective pharmacokinetics in rats after intravenous administration of racemic epinephrine for the first time. The pharmacokinetic results indicated that the disposition of epinephrine enantiomers was stereoselective and chiral inversion did not occur in rats.
研究领域:
分析化学
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药物代谢
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神经生物学
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DOI
高影响因子
Chinese Journal of Natural Medicines
·
2021
·
IF 3
Zong-Chao HONG,Quan CAI,He-Zhen WU,Yan-Fang YANG,Heng FAN,Xue-Yun DUAN
Ulcerative colitis (UC) is a chronic refractory non-specific intestinal inflammatory disease that is difficult to be cured. The discovery of new ulcerative colitis-related metabolite biomarkers may help further understand UC and facilitate early diagnosis. It may also provide a basis for explaining the mechanism of drug action in the treatment of UC. Compound Sophorae Decoction (CSD) is an empirical formula used in the clinical treatment of UC. Although it is known to be efficacious, its mechanism of action in the treatment of UC is unclear. The purpose of this study was to investigate the changes in endogenous substances in UC rats and the effects of CSD on metabolic pathways using the metabonomics approach. Metabolomics studies in rats with UC and normal rats were performed using LC-MS/MS. Rats with UC induced using TNBS enema were used as the study models. Metabolic profiling and pathway analysis of biomarkers was performed using statistical and pathway enrichment analyses. 36 screened potential biomarkers were found to be significantly different between the UC and the normal groups; it was also found that CSD could modulate the levels of these potential biomarkers. CSD was found to be efficacious in UC by regulating multiple metabolic pathways.
研究领域:
药理学
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代谢组学
·
胃肠病学
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中医
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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
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药物分析
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生物化学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2022
·Vol. 15
·期 9
·1104
·
IF 5.215
Yin Huang,Fang Yang,Linling Guo,Yan Xu,Xiaxia Yu,Zunjian Zhang,Yuxin Zhang
Doxorubicin (DOX) is an essential component in chemotherapy, and Astragali Radix (AR) is a widely used tonic herbal medicine. The combination of DOX and AR offers widespread, well-documented advantages in treating cancer, e.g., reducing the risk of adverse effects. This study mainly aims to uncover the impact of AR on DOX disposition in vivo. Rats received a single intravenous dose of 5 mg/kg DOX following a single-dose co-treatment or multiple-dose pre-treatment of AR (10 g/kg × 1 or × 10). The concentrations of DOX in rat plasma and six tissues, including heart, liver, lung, kidney, spleen, and skeletal muscle, were determined by a fully validated LC-MS/MS method. A network-based approach was further employed to quantify the relationships between enzymes that metabolize and transport DOX and the targets of nine representative AR components in the human protein–protein interactome. We found that short-term (≤10 d) AR administration was ineffective in changing the plasma pharmacokinetics of DOX in terms of the area under the concentration–time curve (AUC, 1303.35 ± 271.74 μg/L*h versus 1208.74 ± 145.35 μg/L*h,p> 0.46), peak concentrations (Cmax, 1351.21 ± 364.86 μg/L versus 1411.01 ± 368.38 μg/L,p> 0.78), and half-life (t1/2, 31.79 ± 5.12 h versus 32.05 ± 6.95 h,p> 0.94), etc. Compared to the isotype control group, DOX concentrations in six tissues slightly decreased under AR pre-administration but only showed statistical significance (p< 0.05) in the liver. Using network analysis, we showed that five of the nine representative AR components were not localized to the vicinity of the DOX disposition-associated module. These findings suggest that AR may mitigate DOX-induced toxicity by affecting drug targets rather than drug disposition.Keywords:Adriamycin;drug disposition;combination therapy;LC-MS/MS;network
研究领域:
药理学
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肿瘤学
·
中药学
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分析化学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 15
·5634
·
IF 4.6
Chen Sun,Bo Liu,Fengzhi Zhou,Qianqian Zheng,Chunmei Dai,Wei Wei,Guochao Liao,Yuqi Sun
SARS-CoV-2 is a highly contagious and pathogenic virus that first appeared in late December 2019 and caused a global pandemic in a short period. The virus is a single-stranded RNA virus belonging to the Coronaviridae family. Numerous treatments have been developed and tested in response to the pandemic, particularly antiviral drugs. Among them, GS441524 (GS441), a nucleoside antiviral drug, has demonstrated promising results in inhibiting SARS-CoV-2. Nevertheless, the limited oral bioavailability of GS441 restricts its application to patients with the virus. In this study, a novel prodrug of GS441 (NGP-1) with an isobutyl ester and cyclic carbonate structure was designed and synthesized. Its purity and the stability in different artificial digestive juices of NGP-1 was determined with HPLC-DAD methods. The pharmacokinetics of NGP-1 and GS441 were studied in rats via gavage administration. A new LC-MS/MS method was developed to quantitatively analyze GS441 in plasma samples. The results showed that the ka, Cmax, and MRT of converted GS441 from NGP-1 were 5.9, 3, and 2.5 times greater than those of GS441 alone. The Frelof NGP-1 was approximately four-fold that of GS441, with an AUC0–∞of 9716.3 h·ng mL−1. As a prodrug of GS441, NGP-1 increased its lipophilicity, absorption, and bioavailability, indicating that it holds promise in improving the clinical efficacy of anti-SARS-CoV-2 medications.Keywords:anti-SARS-CoV-2;prodrug of GS441524;purity;stability and pharmacokinetics;oral bioavailability;LC-MS/MS
研究领域:
药理学
·
病毒学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
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