JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Fenglun Zhao,Zheng Xiang,Junping Han,Jie Pan,Yuchen Qu,Kai Fan,Zhiqiang Wu,Delai Xu,Yunli Yu,Zhu Shen,Cunjin Su
In December 2021, the U.S. Food and Drug Administration (FDA) granted emergency authorization for Paxlovid® as an antiviral treatment for COVID-19. Paxlovid® is composed of two tablets, nirmatrelvir and ritonavir. Dose adjustment is necessary in cases of renal insufficiency. The aim of present study is to establish a LC–HRMS method for simultaneous determination of nirmatrelvir/ritonavir in human serum for therapeutic drug monitoring. Internal standard saquinavir was added in 25 μL human serum samples, and then the samples were precipitated with methanol. The analytes were separated by gradient elution on a C18 column, using a mobile phase of 0.1 % formic acid-water and methanol, at a flow rate of 0.4 mL/min. The injection volume was 2 μL, and the analysis time was 5 min. The determination of the analytes was performed by electrospray ionization in positive mode by full mass monitoring. The detected ions of nirmatrelvir, ritonavir and saquinavir were m/z 500.24792, 721.32004 and 671.39155, respectively. The linear concentration range for nirmatrelvir was 78.13–20000 ng mL −1 , for ritonavir was 15.63–4000 ng mL −1 (r 2 ＞0.9900). The accuracy ranged from 87.45 %∼104.63 %, and the intra-day and inter-day precision RSD was <15 %. The recovery of nirmatrelvir ranged from 98.72 %∼109.83 %, and that of ritonavir was 95.41∼112.36 %. The matrix effect of nirmatrelvir was 88.31∼97.73 %, and that of ritonavir was 85.17∼103.05 %. This method was used to measure the trough concentrations of nirmatrelvir/ritonavir in 17 patients. The trough concentration of nirmatrelvir was 1331.7–8352.5 ng/mL, and that of ritonavir was 53.4–1325.5 ng mL −1 , with large individual differences. The method is simple, sensitive, specific, and reproducible, and can be used for monitoring the blood concentration and pharmacokinetic study of nirmatrelvir/ritonavir in COVID-19 patients.
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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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2020
·Vol. 34
·期 9
·e4870
·
IF 1.728
Jiping Yi,Bin Chen,Yongzheng Bao,Jingyu Wang
In this study, a simple and reliable LC–MS/MS method was first proposed for the simultaneous determination of TUG-891 and its metabolites TUG-891-alcohol, TUG-891-aldehyde, and TUG-891-acid in rat plasma. The analytes and fasiglifam (internal standard) were extracted from plasma samples with acetonitrile and separated using an Acquity BEH C 18 column (1.7 μm, 2.1 × 50 mm) with water containing 0.05% ammonium hydroxide and acetonitrile containing 0.05% ammonium hydroxide as the mobile phase. A Q-Exactive Orbitrap mass spectrometer in full-scan mode was used for mass detection, and the data analysis was obtained using a mass extraction window of 5 ppm. The calibration curves exhibited excellent linearity (correlation coefficient > 0.9981) in the concentration range of 0.5–1000 ng/mL. The lower limit of quantification was 0.5 ng/mL for all analytes. The intra- and inter-day precision was less than 11.31%, and the accuracy ranged from −11.50 to 9.50%. The extraction recovery of the analytes from rat plasma was greater than 82.31%, and no obvious matrix effect was found. The established method was further applied to the pharmacokinetic study of TUG-891, TUG-891-alcohol, TUG-891-aldehyde, and TUG-891-acid in rat after a single dose of 5-mg/kg treatment of TUG-891. The results demonstrated that TUG-891 was rapidly metabolized into its metabolites and the systemic exposures of the metabolites were much higher than those of TUG-891.
研究领域:
分析化学
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药物代谢
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药理学
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DOI
PubMed
高影响因子
Canadian Journal of Chemistry
·
2024
·Vol. 102
·期 9
·
IF 1.1
Bin Chen,Lirong An,Feng Li,Yanan Tang
Monitoring organic pollutants in rainwater is important to understand relations between air pollutants and water safety. Non-targeted liquid chromatography–mass spectrometry (LC–MS) is a powerful tool but because of big differences of pollutants in polarity, ionization efficiency, and low concentrations, it is challenging to detect all pollutants in a single analysis. Chemical derivatization is a widely adapted strategy to fractionate complex samples with enhanced sensitivity and selectivity. Herein, we propose the usage of dansylation as a chemical derivatization method to improve both LC retention and MS ionization of organic pollutants containing amine, hydroxyl, and carboxyl for non-targeted LC–MS analysis. We first evaluated the labeling coverage of dansylation to organic pollutants in water matrix. Using dansyl chloride (DnsCl) and dansyl hydrazine (DnsHz) to label 100 amine- and hydroxyl-containing compounds and 100 carboxyl compounds, respectively, we found DnsCl and DnsHz had over 60% labeling coverage for 8 categories of compounds. Then dansylation was applied to label the rainwater, source water, disinfected rainwater, and drinking water samples. To facilitate the annotation of dansylated compounds, we also established a web-based tool termed DansylFinder. Using DansylFinder, 3889, 5813, 6077, and 4050 tentative annotations were found in rainwater, source water, disinfected rainwater, and drinking water samples by dansylation-based non-targeted LC-HRMS analysis. Four hundred fifty four were persistently detected in all water samples, suggesting significant organic overlaps of the four water samples. In addition, two degradation pathways reported in drinking water disinfection process were also detected in disinfected rainwater, suggesting rainwater is a potential path for air pollutants to infiltrate drinking water system.
研究领域:
环境科学
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分析化学
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DOI
高影响因子
TALANTA
·
2025
·
IF 6.1
Ruiquan Ding,Mengdie Li,Yawen Zhang,Hongyi Liu,Zhenyu Tang,Xiyue Xiong,Yingzhuang Chen,Ming Ma,Bo Chen
The selective analysis of isoprene-containing natural products, such as triterpenoid saponins and prenylated flavonoids, remains a major challenge in analytical chemistry due to their substantial structural diversity and poor ionization efficiency, which hampers their detection in complex matrices like herbal extracts. To address this pressing need, we developed an analytical platform that integrates the Paternò-Büchi (PB) reaction with LC-HRMS, employing 4,4'-dichlorobenzophenone as the derivatization agent. High selectivity was achieved through a novel dual-filtering strategy combining a characteristic neutral loss (Δm/z = 276.03) with a distinctive chlorine isotope signature (M+2:M+3≈9:6). This approach significantly enhanced detection sensitivity for model compounds (up to 3.8-fold) and reduced false-positive signals in complex herbal extracts by up to 79%. The method was successfully validated using Panax notoginseng and Epimedium extracts, enabling the tentative identification of 42 isoprene-containing natural products, including 29 triterpenoid saponins and 13 flavonoids. In addition, the stereoselectivity of the PB reaction provided structural insight into local steric hindrance, critical for analyzing isomeric saponins, and the platform demonstrated excellent reproducibility, with relative standard deviations (RSDs) below 5.0%. This study presents a robust and highly selective platform for functional group-specific analysis, offering a powerful new tool for natural product research. By significantly enhancing the accuracy and efficiency of isoprenoid screening, it facilitates the discovery of bioactive compounds and holds promise for broad applications in metabolomics, herbal medicine quality control, and the discovery of novel drug leads from natural sources.
研究领域:
分析化学
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天然产物化学
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代谢组学
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植物化学
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质谱分析
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DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2026
·
IF 3.6
Peng Li,Xianqing Yu,Jiamin Wu,Gengyao Qin,Hong Zhang,Weiqun Cao,Mingshe Zhu,Liang Shen,Yi Tao
Vutrisiran is a GalNAc-conjugated small interfering RNA (siRNA) therapeutic approved for targeted hepatic delivery and long-acting gene silencing; however, detailed in vitro and in vivo metabolism data have not been published. In this study, a sensitive LC–HRMS platform was established to systematically evaluate the metabolism and disposition of Vutrisiran in rats following administration of a low, pharmacologically relevant dose (3 mg/kg). Vutrisiran exhibited high systemic metabolic stability, with intact parent drug as the predominant species in plasma and urine. Tissue metabolite profiling revealed distinct organ-specific pathways, including hepatic GalNAc cleavage followed by slow 3′-exonuclease–mediated degradation, and a low abundant but unique kidney-specific 5′-truncation of the sense strand (SS 5′ n-4). Renal excretion was the primary route for elimination of intact drug, whereas biliary excretion was responsible for clearance of extensively catabolized fragments. The overall excretion pattern was consistent with that reported for other GalNAc-conjugated oligonucleotides. These rat metabolic profiling data provide insight into the disposition of Vutrisiran in humans and represent the first reported in vivo disposition characterization of Vutrisiran. The LC–HRMS platform developed in this study enabled highly sensitive metabolite profiling and identification. A semi-quantitative approach based on MS peak area integration was validated by demonstrating close numerical agreement with UV detection. This platform supports metabolite profiling in plasma and target tissues for PK/PD studies and rapid disposition characterization in animals and may serve as an alternative or pilot approach to inform the design and necessity of human radiolabeled mass-balance studies for oligonucleotide therapeutics.
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PubMed
高影响因子
FOOD CHEMISTRY
·
2026
·
IF 10.4
Xinrui Yang,Xiaoling Chen,Gaohan Li,Yang Zhou,Qinhua Chen,Jinjun Hou,Changwu Zheng,Zijia Zhang,Wanying Wu
Areca nut ( Areca catechu L.) is a widely consumed food and medicinal plant with both nutritional value and documented health risks. To comprehensively characterize its chemical composition and spatial distribution, we developed an integrated analytical platform combining solid-phase extraction (SPE), offline two-dimensional liquid chromatography with high-resolution mass spectrometry (2D-LC-HRMS), and desorption electrospray ionization mass spectrometry imaging (DESI-MSI). This approach enriched trace constituents while minimizing matrix interference, enabling the identification of 323 compounds-including terpenes and triterpenoids (89), alkaloids (52), flavonoids (31), lignans (17), and steroids (12). A pH-orthogonal separation system (alkaline and acidic modes) significantly improved resolution of structurally similar, low-abundance compounds. Spatial analysis via DESI-MSI revealed three distribution patterns: seed-specific enrichment, pericarp enrichment, and uniform distribution. By integrating compositional and spatial data, this study offers new insights into the pharmacological basis, potential toxicity mechanisms, and safe applications of areca nut in food systems.
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PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Yuqing Zhao,Yue Yang,Mingshe Zhu,Chongzhuang Tang
Metabolite profiling and identification of oligonucleotide-based therapeutics (OBTs) is important in drug discovery and development. Conventional liquid chromatography-high resolution mass spectrometry (LC-HRMS) methods (using ProMass, BioPharma Finder) are effective for targeted analysis of predictable nuclease-derived metabolites but often miss unexpected non-nuclease-mediated ones. This study aimed to develop a universal analytical workflow for comprehensive metabolite profiling of multiple classes OBTs by integrating BioPharma Finder for targeted identification with a Background Subtraction Filter (BSF) for untargeted detection of unexpected biotransformation products. Inclisiran, a GalNAc-conjugated siRNA, was used as a model compound. Samples incubated with rat, monkey, and human liver S9 fractions were analyzed by the LC-HRMS workflow. As a result, a total of 25 (22 predicted +3 unpredicted) inclisiran metabolites were identified across the three species. BioPharma Finder enabled rapid and sensitive identification of 22 predicted metabolites, supported by automated fragment ion assignment. The BSF data processing revealed 22 metabolites not present in control samples, including SS-1GalNAc, SS-2GalNAc, and SS-3GalNAc, which were missed by BioPharma Finder and likely formed via β- N -acetylglucosaminidase-mediated biotransformation. The structures of BSF-detected metabolites were confirmed by comparison with BioPharma Finder-identified metabolites or characterized through manual MS/MS interpretation. Product ion spectra of these metabolites showed weak or absent diagnostic ion ( m / z 94.936), a characteristic fragment of phosphorothioate-containing oligonucleotides, suggesting that the product ion filtering of this ion exhibits limited utility in discovering inclisiran metabolites. Overall, the integrated LC-HRMS workflow shows strong potential as a universal platform for biotransformation studies of OBTs.
研究领域:
药物分析
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代谢组学
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药物代谢
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生物治疗
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质谱分析
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寡核苷酸治疗
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2024
·
IF 5.7
Caiming Tang,Yizhe Zhu,Ruifen Zheng,Ling Liu,Yan-Hong Zeng,Xiao-Jun Luo,Bi-Xian Mai
Background N,N′-disubstituted p -phenylenediamine-quinones (PPDQs) are oxidization derivatives of p -phenylenediamines (PPDs) and have raised extensive concerns recently, due to their toxicities and prevalence in the environment, particularly in water environment. PPDQs are derived from tire rubbers, in which other PPD oxidization products besides reported PPDQs may also exist, e.g., unknown PPDQs and PPD-phenols (PPDPs). Results This study implemented nontarget analysis and profiling for PPDQ/Ps in aged tire rubbers using liquid chromatography-high-resolution mass spectrometry and a species-specific algorithm. The algorithm took into account the ionization behaviors of PPDQ/Ps in both positive and negative electrospray ionization, and their specific carbon isotopologue distributions. A total of 47 formulas of PPDQ/Ps were found and elucidated with tentative or accurate structures, including 25 PPDQs, 18 PPDPs and 4 PPD-hydroxy-quinones (PPDHQs). The semiquantified total concentrations of PPDQ/Ps were 14.08–30.62 μg/g, and the concentrations followed the order as: PPDPs (6.48–17.39) > PPDQs (5.86–12.14) > PPDHQs (0.16–1.35 μg/g). Significance The high concentrations and potential toxicities indicate that these PPDQ/Ps could seriously threaten the eco-environment, as they may finally enter the environment, accordingly requiring further investigation. The analysis strategy and data-processing algorithm can be extended to nontarget analysis for other zwitterionic pollutants, and the analysis results provide new understandings on the environmental occurrence of PPDQ/Ps from source and overall perspectives.
研究领域:
环境科学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Tongtong Jia,Shaolun Ouyang,Wenrui Chen,Ting Zhang,Mengqi Lu,Xiuying Zhou,Hongtao Lei,Xiaoqun Wei
To get rid of the singularity of the detection of veterinary drug residues in liquid milk, a high-throughput determination was developed for 126 VDRs in 17 categories in liquid milk based on the one-step extraction coupled with LC-HRMS (UPLC-Q-Exactive-Orbitrap-MS). The results showed that adding 2.5 mL of 0.1 mol/L Na2EDTA-McIlvaine in acetonitrile-methanol extractant (50:50, V/V) could effectively improve the response intensity of veterinary drug residues in liquid milk, reduce the matrix effect and eliminate the need for expensive SPE purification. The established external standard quantitative method has a LOD of 0.01–0.30 μg/L for all categories of veterinary drug residues, good linearity in the concentration range of LOQ of 0.03–1.00 μg/L, and correlation coefficients (r 2 ) were all greater than 0.995. The spike recoveries at all three levels were between 80.30% and 119.95%. The positive detection rate of this method in 128 actual samples was 8.59%.
研究领域:
分析化学
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食品科学
·
兽医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2026
·
IF 3.4
Ting Yu,Yuan Sun,Fang-Ning Qiu,Ke Liu,Chun-Lu Liu,Qiu-Yi Pu,Hui-Jun Li
Paris species, known as “Chonglou” in traditional Chinese medicine, have been used clinically for millennia. Nevertheless, the variation patterns of their chemical constituents and biological activities among different species are still poorly understood and urgently need to be elucidated. Current research has largely focused on a few pharmacopoeial species, while many with ethnomedicinal value remain scientifically unexplored. This study presents the first integrated metabolomic and pharmacological comparison of two pharmacopoeial species, P. polyphylla Smith var. chinensis (PPC) and P. polyphylla Smith var. yunnanensis (PPY), with two ethnomedicinal species, P. thibetica France (PT) and P. fargesii France (PF). A comprehensive phytochemical profile was established using UPLC-Q-TOF-MS/MS, identifying 119 compounds, 85.7% of which were steroidal saponins. Significant inter-species variation in total saponin content was observed, with PF showing the highest average. Multivariate statistical analysis successfully identified species-specific markers and revealed unexpected chemotaxonomic affinities. Pharmacologically, all four species exhibited significant dual bioactivities. They demonstrated potent hemostatic effects, significantly reducing tail bleeding time and directly inducing platelet aggregation. Concurrently, the extracts showed considerable anti-hepatocarcinoma activity. Mechanistically, this anti-cancer effect involved the induction of S -phase cell cycle arrest and apoptosis, which were associated with down-regulation of Bcl-2 and suppression of c-Myc signaling. The above-mentioned findings confirmed PF and PT as promising complementary resources to the official pharmacopoeial species. This work provides a critical chemical and pharmacological foundation for their quality standardization and potential therapeutic application in hemostasis and liver cancer management.
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2019
·
IF 3.858
Enming Miao,Nazhen Zhang,Shiwei Lu,Yufeng Hu,Lin Fu,Hao Zhou,Jingjing Zhan,Minghuo Wu
A simple magnetization method was developed for the preparation of magnetic materials from conventional solid phase packing though coprecipitation and solvothermal approaches. And the prepared magnetic materials were used for magnetic solid phase extraction (MSPE) of biogenic amines (BAs) from beers. Furthermore, to improve the analytical throughput, a solid phase “on-situ” quadraplex isotope dimethyl labeling method was developed for the quantification of BAs by liquid chromatography-high resolution mass spectrometry (LC HRMS). Compared to conventional in-solution labeling, the “on-situ” labeling could simplify the sample preparation procedure and efficiently remove the residuals such as inorganic salts and excessive labeling reagents. The quadraplex labeling, which enabled three real samples and one internal standard sample to be analyzed simultaneously in a single LC HRMS run. For the tested 8 BAs (cadaverine, phenethylamine, spermine, spermidine, tyramine, histamine, putrescine and tryptamine), LODs of 0.02–0.05 μg/L and LOQs of 0.05–0.1 μg/L were achieved at good reproducibility (RSD of 0.5–4.6% and 2.2–7.0% for intra- and inter-day reproducibility, respectively). With this method, six beer samples were analyzed, and these 8 BAs were all detected in the range of low μg/L to 2.9 mg/L, which were lower than maximal residual level (MRL) required in the regulations of China and EU.
研究领域:
分析化学
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食品科学
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质谱分析
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2020
·
IF 5.339
Minghuo Wu,Enming Miao,Wenxue Xu,Weiping Xu,Yufeng Hu,Jingjing Zhan,Hao Zhou
Estrogens distribute widely in the environment as endocrine-disrupting chemicals (EDCs), which have to be monitored to evaluate their environmental impact. Aim to improve the analytical throughput of liquid chromatography-high resolution mass spectrometry (LC-HRMS), a quadruplex stable isotope dansylation method was developed, with which three real samples could be quantitatively analyzed in one injection. As the estrogens were at trace level in complex matrices, magnetic solid-phase extraction (MSPE) was applied to enrich these analytes and remove the interfaces. By integrating MSPE and quadruplex stable isotope dansylation, a solid-phase quadruplex labeling method was developed for the LC-HRMS analysis of estrogen analogues . For the tested seven estrogens, the developed method showed low detection limits (0.1–0.5 ng/L for pond water and 0.01–0.05 μg/kg for poultry manure), good precision (RSD < 5.5%) and accuracy (96.8–108.3%). The method was applied in the determination of estrogens in environmental samples, and the results revealed that all the tested estrogens were present in the estuary water (unquantifiable to 71.2 ng/L) and chicken manure (undetectable to 25.43 μg/kg).
研究领域:
环境科学
·
分析化学
·
环境监测
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DOI
高影响因子
危险品化学品经营许可证（带存储）