JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2016
·
IF 3.169
Yidi Yang,Xi Zhu,Fei Zhang,Wei Li,Ying Wu,Li Ding
Stress testing was carried out under acidic, alkaline, oxidative, thermal and photolytic conditions to evaluate the intrinsic stability of posaconazole injection. A total of four degradation products were detected and the drug was found to be susceptible to oxidative and thermal degradations. Three unknown degradants formed under oxidative stress condition were isolated by preparative HPLC and unambiguously elucidated by LC–TOF/MS, LC–MS/MS, 1 H NMR, 13 C NMR and 2D NMR techniques. Based on the spectrometric and spectroscopic information, these novel degradation products were unequivocally assigned as the N-oxides of posaconazole. Probable mechanisms for the formation of the degradants were proposed. A new and selective HPLC method was developed and validated to separate, detect and quantify all the degradants in posaconazole injection.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Qiao-Lai Wang,Pei-Xi Zhang,Rui Shen,Meng Xu,Liang Han,Xuan Shi,Zi-Rui Zhou,Jing-Yi Yang,Jie-Qing Liu
Ethnopharmacological relevance Arbutin is a naturally occurring glucoside extracted from plants, known for its antioxidant and tyrosinase inhibiting properties. It is widely used in cosmetic and pharmaceutical industries. With in-depth study of arbutin, its application in disease treatment is expanding, presenting promising development prospects. However, reports on the metabolic stability, plasma protein binding rate, and pharmacokinetic properties of arbutin are scarce. Aim of the study The aim of this study is to enrich the data of metabolic stability and pharmacokinetics of arbutin through the early pre-clinical evaluation, thereby providing some experimental basis for advancing arbutin into clinical research. Materials and methods We developed an efficient and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for determining arbutin in plasma. We investigated the metabolic and pharmacokinetic properties of arbutin through in vitro metabolism assay, cytochrome enzymes P450 (CYP450) inhibition studies, plasma protein binding rate analysis, Caco-2 cell permeability tests, and rat pharmacokinetics to understand its in vivo performance. Results In vitro studies show that arbutin is stable, albeit with some species differences. It exhibits low plasma protein binding (35.35 ± 11.03% ∼ 40.25 ± 2.47%), low lipophilicity, low permeability, short half-life (0.42 ± 0.30 h) and high oral bioavailability (65 ± 11.6%). Arbutin is primarily found in the liver and kidneys and is eliminated in the urine. It does not significantly inhibit CYP450 up to 10 μM, suggesting a low potential for drug interactions. Futhermore, preliminary toxicological experiments indicate arbutin's safety, supporting its potential as a therapeutic agent. Conclusion This study provides a comprehensive analysis the drug metabolism and pharmacokinetics (DMPK) of arbutin, enriching our understanding of its metabolism stability and pharmacokinetics properties, It establishes a foundation for further structural optimization, pharmacological studies, and the clinical development of arbutin.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Chemistry
·
2025
·Vol. 19
·期 1
·180
·
IF 4.6
Xiaoyu Yang,Wanling Lin,Yushang Zhao,Chaoyue Zhao,Fei Zhou,Dong Wang,Zhihong Yue,Lin Pei,Mei Jia,Bin Cao,Lin-Lin Cao,Hui Wang
“Xiannuoxin” (simnotrelvir/ritonavir) is a novel anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drug developed in China, which plays an antiviral role by inhibiting 3C-like protease (3CL pro ). At present, it has been put into clinical use, while a simple, accurate and sensitive detection method is urgently needed for the quantification of simnotrelvir/ritonavir in human serum and bronchoalveolar lavage fluid (BALF) to ensure safe and efficacious antiviral therapeutics. In this study, we developed a liquid chromatography tandem mass spectrophotometry (LC-MS/MS) method for the simultaneous determination of simnotrelvir, ritonavir and urea concentrations in human serum and BALF samples. Prior to LC-MS/MS analysis, a user-friendly, one-step pre-analytical process was conducted, followed by a rapid chromatographic run lasting 3 min. This was then succeeded by positive and negative electrospray ionization and detection using a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode. Subsequently, the LC-MS/MS method underwent a comprehensive validation in aspects such as sensitivity (LoQs of 2.5 ng/mL, 0.1 ng/mL, and 1 μg/mL for simnotrelvir, ritonavir and urea), linearity, carryover, precision, trueness (recovery rates of simnotrelvir, ritonavir and urea were between 85 and 115%), matrix effect (within 85-115%) and stability (stable for 72 h at room temperature). The validation results demonstrated that this LC-MS/MS method was robust and reliable. Notably, we can use the urea dilution correction method to calculate the concentrations of simnotrelvir and ritonavir in epithelial lining fluid (ELF), which is of great significance for evaluating the effectiveness and safety of antiviral drug treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 6
·e70108
·
IF 1.7
Ancheng Gu,Chuwen Zhang,Dan Li,Bohong Cen,Wanwen Cao,Zhongyuan Xu
Dapagliflozin is a widely used sodium-glucose cotransporter 2 inhibitor that has been approved for the treatment of Type 2 diabetes. In this study, we present a simple and sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method for the simultaneous quantification of dapagliflozin and its metabolite, dapagliflozin 3-O-glucuronide (D3OG). The experiments were conducted using an Agilent G6495B triple quadrupole mass spectrometer coupled with an Agilent 1290 Infinity II HPLC system, featuring a Poroshell 120 EC-C18 column. Gradient elution was performed with ammonium formate (10 mM) and methanol as the mobile phase. The G6495B was operated in negative ion mode with electrospray ionization and multiple reaction monitoring. The quantitative method was validated according to FDA and EMA guidelines, assessing parameters such as selectivity, linearity, accuracy, precision, dilution integrity, stability, and recovery. Methanol was used as a protein precipitant during sample preparation, resulting in consistent extraction recoveries ranging from 91% to 96% for all analytes. The linear range for the analytes was established at 2–800 μg/L with a sample volume of 100 μL. This validated method is sufficient for the simultaneous quantification of dapagliflozin and D3OG in plasma and has been successfully applied in pharmacokinetic studies, bioequivalence assessments, and clinical therapeutic monitoring. Trial Registration: Chinese Clinical Trial identifier: ChiCTR2100044600
研究领域:
分析化学
·
药理学
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2020
·
IF 3.209
Yanfei Chen,Zhaoliang Hu,Wenzhu Qi,Shuxiao Gao,Jing Jiang,Shixiao Wang,Lei Xu,Xin Xu,Min Song,Taijun Hang
Chinese herbal drugs are often combined with chemotherapy drugs for the treatment of cancers. However, the combination administrations often do not have scientifically sound bases established on full preclinical and clinical investigations. A commonly used anti-colon-cancer herb-drug pair, irinotecan (CPT-11) hydrochloride injection and Kang’ai (KA) injection was taken as an example to investigate the possible pharmacokinetic interactions between Chinese herbal drugs and chemotherapy injections to determine the potential adverse drug reactions (ADRs). Rats were randomly divided into three groups and received 20 mg/kg CPT-11 injection 15 min after administration of 4 mL/kg saline for the CPT-11 single administration group and 4 mL/kg KA injection for the separated co-administration group, respectively. In the pre-mixed co-administration group, rats received a mixture of 20 mg/kg CPT-11 injection and 4 mL/kg KA injection. Blood samples were collected at 10 pre-determined time points between 0 and 24 h. The tissue samples were collected at 5 and 8 min after the injections, respectively. A reliable LC–MS/MS method was established for the simultaneous determination of CPT-11 and its metabolites, SN-38, SN-38 G and APC in the rat plasma and tissue samples, after full confirmation of two injections chemical and stability compatibilities. Compared to the C 0 (5129 ± 757 ng/mL) and AUC 0-t (7858 ± 1307 ng h/mL) of CPT-11 in the CPT-11 single administration group, the C 0 (4574 ± 371 ng/mL) and AUC 0-t (8779 ± 601 ng h/mL) after the separated co-administration remained unchanged, but the pre-mixed co-administration resulted with a significant increased C 0 (29,454 ± 12,080 ng/mL) and AUC 0-t (15,539 ± 5165 ng h/mL) (p < 0.05). Since the exposures of CPT-11 in most tissues in the pre-mixed co-administration group were dramatically lower than the separated co-administration group, the increased CPT-11 plasma concentration may be produced by the delayed tissue distribution because of the encapsulation by the components contained in KA injection, such as polysaccharides. Similar differences were also found in its metabolite, SN-38 G. There are obvious herb-drug interactions between CPT-11 injection and KA injection after the pre-mixed co-administration. The resulting excessive CPT-11 in the plasma may lead to many serious ADRs. Therefore, the full evaluation of herb-drug interactions is necessary and inappropriate combinations should be avoided.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY
·
2019
·
IF 1.117
Leilei Zhao,Qiong Jiang,Sitong Luo,Jie Shen,Xinjun Xu
Hepatic stimulator substance (HSS) is prepared by the freeze–thaw method on a large scale, but it is time-consuming and inefficient. It is necessary to find a better method to improve the efficiency and yield of HSS. In this study, HSS was prepared by enzymatic hydrolysis of neonatal porcine liver with trypsin, papain, dispase, and alcalase. Relatively, dispase was found to be the best enzyme, based on the results of the degree of hydrolysis and MTT assay. Box–Behnken design-response surface method was used to optimize the conditions, which were as follows: enzyme (dispase) concentration, 4164 U/g; substrate concentration, 7% (w/v); hydrolysis time, 4.3 hr; temperature, 45 °C; and pH, 6.5. The degree of hydrolysis was (54.99 ± 1.57)%. Shotgun proteomics coupled with Gene Ontology (GO) analysis based on the PANTHER classification system was used to screen proteins from neonatal porcine liver. The results profiled the proteins into biological processes, molecular functions, and cellular components, thus laying a foundation for further studies on components involved in and mechanisms of liver regeneration. Overall, the results suggest that enzymatic hydrolysis might be a promising method for industrial application.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2019
·
IF 2.983
Xue-Mei Han,Yan-Jie Qin,Ying Zhu,Xin-Lin Zhang,Nan-Xi Wang,Ying Rang,Xue-Jia Zhai,Yong-Ning Lu
Sensitive and comprehensive measurement of systemic metabolites of tryptophan, phenylalanine and glutamate metabolism in biological samples is effective for understanding the pathogenesis of depression and other neurological diseases. Therefore, this study developed an underivatized liquid chromatography tandem mass spectrometry (LC–MS/MS) method for simultaneous monitoring the 3 components of glutamate metabolism in rat hippocampus and 11 components of tryptophan and phenylalanine metabolism in rat hippocampus, plasma and urine, and applied it to investigate their changes in rats induced by chronic unpredictable mild stress (CUMS). The investigated analytes are as follows: tryptophan, serotonin, 5-hydroxyindoleacetic acid, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, phenylalanine, tyrosine, tyramine, glutamate, glutamine and gamma-aminobutyric acid. The method was verified to be sensitive and effective with satisfactory linearity, accuracies in the range of 78.2%–120.4%, and precisions less than 17.8% for all identified analytes. A series of significant changes in CUMS-induced rats can be detected: tryptophan, serotonin and tyrosine levels decreased and quinolinic acid increased in both hippocampus and plasma. In addition, the kynurenine/tryptophan ratios increased in hippocampus and plasma, the kynurenic acid/quinolinic acid ratios of plasma and urine were significantly reduced. These findings demonstrated that the CUMS procedure could lead to the central and peripheral imbalances of tryptophan and phenylalanine metabolism. In conclusion, a LC–MS/MS method for simultaneous measurement of several neurotransmitters in rat hippocampus, plasma and urine was developed and successfully applied to investigation of the central and peripheral changes in CUMS-induced rats. The method would be expected to provide applicability to the study of the mechanisms of depression and other related diseases associated with these neurotransmitters.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2019
·Vol. 43
·期 3
·590-597
·
IF 2.516
Hong Pan,Feng Yang,Daiyuan Xiang,Fuguo Shi
Xanthii Fructus is extensively used as an herbal medicine. Ingestion of this herb is associated with severe hepatotoxicity and nephrotoxicity. Atractyloside and carboxyatractyloside are two dominative toxic constituents in Xanthii Fructus. However, their pharmacokinetic study is lacking. In this study, a novel high-performance liquid chromatography-tandem mass spectrometry method was developed to simultaneously quantify the rat plasma concentrations of atractyloside and carboxyatractyloside. After protein precipitation, the analytes were chromatographic separated on a ZORBAX Eclipse Plus column (2.1 × 150 mm id, 5 µm) under gradient elute. In the negative electrospray ionization mode, the transitions at m/z 725.3→645.4 for atractyloside, m/z 769.3→689.4 for carboxyatractyloside, and m/z 479.2→121.1 for paeoniflorin (the internal standard) were acquired by multiple reaction monitoring. This analytical method showed good linearity over 1–500 ng/mL for atractyloside and 2–500 ng/mL for carboxyatractyloside with acceptable precision and accuracy. No matrix effect, instability and carryover occurred in the analysis procedure. The extraction recoveries were greater than 85.0%. This method was applied to a preliminary pharmacokinetic study by orally administering Xanthii Fructus extract (9 g/kg) to rats, which was useful to evaluate the role of these two compounds in Xanthii Fructus-induced toxicity.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2015
·
IF 2.912
Xin Li,Man-Man Wang,Guo-Ying Zheng,Lian-Feng Ai,Xue-Sheng Wang
A hydrophobic monolith (10 mm × 2.1 mm i.d.) was developed as a reusable online solid-phase extraction (SPE) sorbent coupled with LC-MS/MS for the rapid determination of five avermectin residues in foodstuffs of both plant and animal origin. The online SPE was achieved using a 10 mmol/L ammonium acetate solution as the loading solvent, and acetonitrile (MeCN) was selected for the washing step. After being transferred from the monolith into a C18 analytical column using MeCN, the analytes were analyzed by LC-MS/MS using MeCN/0.1% NH4OH (10:90, v/v) as the mobile phase. The detection limit was 2 μg/kg for five avermectins, and the recoveries in fresh pear, chili seed, bovine muscle, and milk ranged from 71.8% to 101.3% with relative standard deviations of less than 8.94%. The online SPE and determination were achieved within 15 min, and the monolithic extractor was reusable for more than 500 experiments.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2015
·Vol. 29
·期 11
·1737-1743
·
IF 1.723
Xue-jia Zhai,Fen Chen,Chao-ran Zhu,Yong-ning Lu
Many amino acid neurotransmitters in urine are associated with chronic stress as well as major depressive disorders. To better understand depression, an analytical LC-MS/MS method for the simultaneous determination of 11 underivatized neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate, pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single analytical run was developed. The advantage of this method is the simple preparation in that there is no need to deconjugate the urine samples. The quantification range was 25–12,800 ng mL −1 with >85.8% recovery for all analytes. The nocturnal urine concentrations of the 11 neurotransmitters in chronic unpredictable mild stress (CUMS) model rats and control group ( n = 12) were analyzed. A series of significant changes in urinary excretion of neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate and tyramine concentrations were significantly lower in the CUMS group. In addition, the urinary concentrations of tryptophan as well as tyrosine were significantly higher in chronically stressed rats. This method allows the assessment of the neurotransmitters associated with CUMS in rat urine in a single analytical run, making it suitable for implementation as a routine technique in depression research. Copyright © 2015 John Wiley & Sons, Ltd.
✓ 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
·
2014
·
IF 2.694
Zhiyong Zhao,Qinxiong Rao,Suquan Song,Na Liu,Zheng Han,Jiafa Hou,Aibo Wu
A simple and reliable method for simultaneous determination of deoxynivalenol-3-glucoside and major type B trichothecenes (deoxynivalenol, nivalenol, fusarenon X, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol and deepoxy-deoxynivalenol) in animal feed and raw materials has been developed and validated in this study. The method was based on an improved dispersive solid-phase extraction (DSPE) followed by analysis using high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Also, matrix-matched calibration curve ( R 2 > 0.99) was employed to minimize matrix effects and ensure accurate quantification. The recoveries during sample preparation process (including extraction and clean-up) ranged from 79.03% to 118.39%, with intra-day and inter-day relative standard deviation lower than 20% for all the analytes. The limit of quantification ranged from 5.0 μg/kg for deoxynivalenol to 13.6 μg/kg for fusarenon X. The validated method was successfully applied to the analysis of animal feed and corn. The pilot study showed that 37 out of 41 samples were contaminated with deoxynivalenol-3-glucoside at the levels of 6.0–121.0 μg/kg. Most of the type B trichothecenes were also found with the exception of fusarenon X, at the contaminated levels of 10.0–1382 μg/kg. To the best of our knowledge, this was the first scientific report on the co-occurrence of masked deoxynivalenol and type B trichothecenes in animal feed and raw materials.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2017
·
IF 3.255
Yuan Wang,Qing Li,Yue Dai,Ronghua Pan,Yufeng Xia
A specific and sensitive LC–MS/MS method was established for the simultaneous determination of bergenin, protocatechuic acid and gallic acid, the main active constituents of Saxifraga stolonifera (L.) Meerb. herb, in rat plasma. After fully validated, the method was applied to the comparative pharmacokinetic studies of the three compounds orally administered alone and in combination in the S. stolonifera extract, respectively. The results showed that the pharmacokinetic parameters, including C max , T max , AUC, CL z /F, MRT 0-∞ , were significantly different for both bergenin and protocatechuic acid in the extract as compared to the corresponding compounds administered alone. However, the pharmacokinetic behavior of gallic acid in the extract did not differ from that administered alone. Further studies found that quercetin, coexisting in the herb extract, significantly decreased the glucuronidation of bergenin through inhibiting the activities of UGT1A1 and UGT1A3, and reduced the metabolism of protocatechuic acid by inhibiting the activity of catechol-O-methyltransferase. Quercetin and other flavonoids occurring in the S. stolonifera extract might increase the absorption and improve the bioavailability of bergenin and protocatechuic acid by slowing down the liver metabolism. The findings provide a good guidance for the development and clinical application of S. stolonifera .
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）