Journal of Chromatography B最新文献

{"title":"A proteomics-based study of the mechanism of oxymatrine to ameliorate hepatic fibrosis in mice","authors":"Jing Wu ,&nbsp;Xueqin Jin ,&nbsp;Weihua Li ,&nbsp;Enqi Liu","doi":"10.1016/j.jchromb.2024.124280","DOIUrl":"10.1016/j.jchromb.2024.124280","url":null,"abstract":"<div><h3>Objective</h3><p>This study investigated the protective effect of oxymatrine (OMT) on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in mice and explored its possible targets and signaling pathways.</p></div><div><h3>Methods</h3><p>Male BALB/c mice were randomly divided into blank control, model, positive drug (silymarin), and OMT administration groups, respectively, with 10 mice in each group. Hepatic fibrosis was induced in mice using CCl₄ and the corresponding drug intervention was given. After the final administration, ultrasonography tests, blood tests, and analysis of liver differential proteins using tandem mass tag labeling and liquid chromatography-mass spectrometry were performed.</p></div><div><h3>Results</h3><p>OMT intervention ameliorated CCl₄-induced hepatic fibrosis in mice, significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels, down-regulated the expression of fibrosis factors, such as type IV collagen IV, laminin, type III procollagen III, and alpha-smooth muscle actin, and improved liver function. The results of the proteomic analysis showed that the intervention of OMT significantly down-regulated 130 out of 440 up-regulated proteins and up-regulated 70 out of 294 down-regulated proteins, primarily involving the transient receptor potential (TRP) signaling pathway, the peroxisome proliferator-activated receptors (PPAR) signaling pathway, and the metabolic pathway of arachidonic acid. The main differential proteins involved were Cyp2c37, SCP-2, and Tbxas1. In addition, OMT intervention significantly reversed the expression of sterol carrier protein-2 (SCP2) and upregulated the expression of peroxisome proliferator-activated receptor gamma, Cyp2c37, and transient receptor potential cation channel subfamily V member 1 proteins.</p></div><div><h3>Conclusion</h3><p>OMT inhibited the proliferative capacity of hepatic stellate cells, induced apoptotic properties, and suppressed the development of fibrosis by elevating Cyp2c37/TRP signaling axis activity and upregulating PPAR pathway activity by inhibiting SCP2.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1247 ","pages":"Article 124280"},"PeriodicalIF":2.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive exploration of a traditional Chinese medicinal plant of Magnolia officinalis based on high-coverage mass spectrometry and multidimensional chemical-biological analysis","authors":"Wen-Yu Wang ,&nbsp;Ya-Mei Song ,&nbsp;Jia-Nuo Zhang ,&nbsp;Ming-Yue Zhao ,&nbsp;Wen-Han Pei ,&nbsp;Hui Zhang ,&nbsp;Hai-Bo Yin ,&nbsp;Zhi-Li Xu ,&nbsp;Gui-Zhong Xin ,&nbsp;Ming Xie ,&nbsp;Ting-Guo Kang ,&nbsp;Yue-Hua Chen ,&nbsp;Hui-Peng Song","doi":"10.1016/j.jchromb.2024.124290","DOIUrl":"10.1016/j.jchromb.2024.124290","url":null,"abstract":"<div><p>Magnolia bark is a traditional Chinese medicine used for hypoglycaemia. With the widespread use of Magnolia bark, its resources are facing a serious shortage. To address this issue, a strategy based on high-coverage mass spectrometry (HCMS) and multidimensional chemical-biological analysis (MCBA) was proposed for the comprehensive exploration of <em>Magnolia officinalis</em> which is the main source of Magnolia bark. The strategy is divided into three main steps. In the first step, the stem bark, stem xylem, root bark, root xylem, leaf and rootlet of <em>Magnolia officinalis</em> were comprehensively analyzed using high-coverage mass spectrometry. In the second step, multivariate statistical analysis was used to explore the heterogeneity of the six parts and detect differential chemical components. In the third step, a combination of experimental screening and molecular docking was used to explore α-glucosidase inhibitors from <em>Magnolia officinalis</em>. Multidimensional chemical-biological analysis (MCBA) of <em>Magnolia officinalis</em> was achieved by combining the last two steps. Finally, a total of 103 compounds were identified from the whole plant of <em>Magnolia officinalis</em>. Differential components of stem bark, stem xylem, leaf, root bark, root xylem and rootlet were systematically revealed. A pair of positional isomers, namely magnolol and honokiol, were found to be α-glucosidase inhibitors. The activity of their combination is superior to that of each single compound, indicating that magnolol and honokiol are in a synergistic relationship. This strategy contributes to comprehensive exploitation of functional plants and effective alleviation of resource shortage. This study also provides a research paradigm for other similar traditional Chinese medicinal plants.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1246 ","pages":"Article 124290"},"PeriodicalIF":2.8,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-target metabolomics unravels the effect and mechanism of Lianpu Drink on spleen-stomach damp-heat syndrome","authors":"Jingbo Yu ,&nbsp;Henan Liu ,&nbsp;Jiarong Xiong ,&nbsp;Shanhe Qu ,&nbsp;Xin Xie ,&nbsp;Hongqing Zhao ,&nbsp;Zhengqing Zhu ,&nbsp;Yuhong Wang ,&nbsp;Yue Han","doi":"10.1016/j.jchromb.2024.124281","DOIUrl":"10.1016/j.jchromb.2024.124281","url":null,"abstract":"<div><h3>Background</h3><p>Lianpu Drink (LPY) is a classic prescription for treating spleen-stomach damp-heat syndrome (SSDHS), known for its ability to clear heat and eliminate dampness. However, the underlying mechanisms of LPY in treating SSDHS remain unclear.</p></div><div><h3>Objectives</h3><p>This study aims to use non-target metabolomics to unravel the effects and mechanisms of LPY on SSDHS.</p></div><div><h3>Methods</h3><p>A metabolomics technique based on ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to identify the endogenous small-molecule metabolites in the urine of SSDHS model rats and find the metabolites associated with the LPY treatment of SSDHS. Furthermore, a network pharmacological analysis and molecular docking experiments were used to screen and validate the key metabolic pathways regulated by LPY.</p></div><div><h3>Results</h3><p>LPY exerted therapeutic effects on SSDHS by increasing the levels of motilin and gastrin, reducing the rectal temperature, alleviating the pathological changes in gastric and colonic tissues, and regulating the metabolic pattern in SSDHS rats. A total of 25 different metabolites, including L-histidine, citric acid and isocitric acid, were identified as the potential biomarkers for SSDHS via metabolomics. Among them, 11 metabolites were substantially reversed by LPY, including L-histidine, citric acid, isocitric acid, pantothenic acid, homovanillic acid sulfate, hippuric acid, indole-3-carboxilic acid-O-sulphate, 6-hydroxy-5-methoxyindole glucuronide, 2-phenylethan-ol glucuronide, 3-hydroxydodecanedioic acid and 3-methoxy-4-hydroxy-phenylethyleneglyclol sulfate. The results of network pharmacological analysis and molecular docking experiments validated that LPY ameliorated SSDHS by regulating the citrate cycle and histidine metabolism.</p></div><div><h3>Conclusion</h3><p>We preliminarily investigated the effects and mechanisms of LPY on SSDHS at the level of endogenous small-molecule metabolites. Furthermore, this study provides a novel perspective for objectively evaluating the therapeutic effects, and exploring the mechanisms of Chinese medicinal formulas on SSDHS.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1246 ","pages":"Article 124281"},"PeriodicalIF":2.8,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570023224002903/pdfft?md5=0f1f6c6c7de10fdc1a3526d7db13d1da&pid=1-s2.0-S1570023224002903-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification of florfenicol and its metabolites in fillets of Nile tilapia: Synthesis of metabolites and validation of an on-line solid-phase extraction-ultra high-performance liquid chromatography-tandem mass spectrometry method","authors":"Anna Paula Rocha de Queiroga ,&nbsp;Gabriela Freitas Pereira de Souza ,&nbsp;Inácio Mateus Assane ,&nbsp;Thiago Messias ,&nbsp;Fabiana Pilarski ,&nbsp;Michael Schloter ,&nbsp;Airton Gonçalves Salles Jr. ,&nbsp;Susanne Rath","doi":"10.1016/j.jchromb.2024.124282","DOIUrl":"10.1016/j.jchromb.2024.124282","url":null,"abstract":"<div><p>This study concerns the synthesis of the florfenicol (FF) metabolites florfenicol amine (FFA), florfenicol alcohol (FFOH), and monochloroflorfenicol (FFCl), for their subsequent use as reference standards in On-line solid-phase extraction-ultra high-performance liquid chromatography-tandem mass spectrometry (SPE-UHPLC-MS/MS) analysis. The metabolites were characterized using ¹H and ¹³C NMR, as well as HRMS, and their purities were confirmed by quantitative NMR to ensure analytical reliability. Validation of the developed analytical method showed that it presented acceptable performance, with linearity &gt;0.99 for all the target analytes, accuracies within ±10 % of nominal concentrations, and intra- and inter-day precisions within 15 %. Application of this method to fillets from fish that had been treated with florfenicol (dose of 10 mg/kg bw daily) demonstrated its effectiveness in consistently detecting FF and its metabolites throughout the treatment. The results emphasized the utility of the method for enhancing pharmacokinetic and residue depletion research. The ability to precisely monitor the drug and its metabolites in treated fish provides important insights into florfenicol metabolism, laying the groundwork for further comprehensive profiling studies of metabolites in fish tissue.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1246 ","pages":"Article 124282"},"PeriodicalIF":2.8,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short communications: Exploring temporal fluorescent changes in the composition of human semen stains","authors":"Nihad Achetib ,&nbsp;Susanne Danser ,&nbsp;Kirsa Min ,&nbsp;Zehra Köksal ,&nbsp;Maurice C.G. Aalders ,&nbsp;Annemieke van Dam","doi":"10.1016/j.jchromb.2024.124278","DOIUrl":"10.1016/j.jchromb.2024.124278","url":null,"abstract":"<div><p>Semen traces are considered important pieces of evidence in forensic investigations, especially those involving sexsual offenses. Recently, our research group developed a fluorescence-based technique to accurately determine the age of semen traces. However, the specific compounds resonsible for the fluoresescent behaviour of ageing semens remain unknown. As such, in this exploratory study, the aim is to identify the components associated with the fluorescent behavior of ageing semen traces. In this investigation semen stains and various biofluorophores commonly found in body fluids were left to aged for 0, 2, 4, 7, 14 and 21 days. Subsequently, thin-layer chromatography (TLC) and ultra-performance liquid chromatography (UPLC) mass spectrometry were performed to identify the biofluorophores present in semen. Several contributors to the autofluorescence could be identified in semen stain, these include tryptophan, kynurenine, kynurenic acid, and norharman. The study sheds light on the.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1246 ","pages":"Article 124278"},"PeriodicalIF":2.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570023224002873/pdfft?md5=2a92de685a2671f5b1a70a9ece3483d1&pid=1-s2.0-S1570023224002873-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Streamlined on-column refolding and purification of nanobodies from inclusion bodies expressed as fusion proteins","authors":"Yiwen Zhang ,&nbsp;Yang Guo ,&nbsp;Liang Song ,&nbsp;Wenshuai Liu ,&nbsp;Rui Nian ,&nbsp;Xiying Fan","doi":"10.1016/j.jchromb.2024.124279","DOIUrl":"10.1016/j.jchromb.2024.124279","url":null,"abstract":"<div><p>This study introduces an efficient on-column refolding and purification method for preparing nanobodies (Nbs) expressed as inclusion bodies and fusion proteins. The HisTrap^TM FF system was successfully employed for the purification of the fusion protein FN1-ΔI-CM-2D5. The intein ΔI-CM cleavage activity was activated at 42 °C, followed by incubation for 4 h. Leveraging the remarkable thermal stability of Nbs, 2D5 was further purified through heat treatment at 80 °C for 1h. This method yielded up to 107.2 mg of pure 2D5 with a purity of 99.2 % from just 1L of bacterial culture grown in a shaker flask. Furthermore, this approach successfully restored native secondary structure and affinity of 2D5. Additionally, the platform was effectively applied to the refolding and purification of a polystyrene-binding nanobody (B2), which exhibited limited expression in the periplasmic and cytoplasmic spaces of <em>E. coli</em>. This endeavor resulted in the isolation of 53.2 mg of pure B2 Nb with a purity exceeding 99.5 % from the same volume of bacterial culture. Significantly, this approach restored the native secondary structure of the Nbs, highlighting its potential for addressing challenges associated with expressing complex Nbs in <em>E. coli</em>. Overall, this innovative platform provides a scientifically rigorous and reproducible method for the efficient preparation of Nbs, offering a valuable tool for antibody research and development.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1246 ","pages":"Article 124279"},"PeriodicalIF":2.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of HPTLC method for simultaneous determination of quercetin and kaempferol in leaf extract of Hibiscus mutabilis","authors":"Anusha Srinivas ,&nbsp;Sapna Nehra","doi":"10.1016/j.jchromb.2024.124277","DOIUrl":"10.1016/j.jchromb.2024.124277","url":null,"abstract":"<div><p>The aim of this study was to develop and validate a densitometric High-Performance Thin-Layer Chromatography (HPTLC) method for the simultaneous quantification of quercetin (Q) and kaempferol (K) in <em>Hibiscus mutabilis</em> leaf extracts. The analyses were performed on silica gel 60 F254 plates using a mobile phase composed of toluene, formic acid, and ethyl acetate (6:0.4:4, v/v/v). Detection was carried out at a wavelength of 272 nm using a deuterium and tungsten light source. The method exhibited excellent linearity over the concentration range of 100–600 ng/spot for quercetin and 500–3000 ng/spot for kaempferol, with determination coefficients (r²) of 0.9989 and 0.9973, respectively. The method showed no interferences from the plant matrix. The relative standard deviation (RSD) values for intra- and inter-day precision were less than 2% for both flavonoids. Recovery rates ranged from 97.69% to 99.20% for quercetin and from 89.91% to 95.87% for kaempferol. The limits of detection (LOD) were 190.23 ng/spot for quercetin and 187.23 ng/spot for kaempferol, while the limits of quantification (LOQ) were 570.10 ng/spot for quercetin and 566.12 ng/spot for kaempferol. This validated HPTLC method is reliable, precise, and accurate, making it suitable for the quality control of <em>Hibiscus mutabilis</em> leaf extracts. The study’s findings can be broadly applied to the quality control of herbal products, pharmacological research, and the development of nutraceuticals. The method’s ability to provide rapid and accurate quantification makes it an invaluable tool for researchers across various disciplines.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1246 ","pages":"Article 124277"},"PeriodicalIF":2.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel method for the simultaneous determination of drugs of abuse, ethyl glucuronide and synthetic opioids in human hair through a single digestion, purification and analysis in LC-MS/MS","authors":"D. Vandelli ,&nbsp;F. Palazzoli ,&nbsp;P. Verri,&nbsp;V. Castagnetti,&nbsp;C. Profeta,&nbsp;A. Borghi,&nbsp;R. Cecchi","doi":"10.1016/j.jchromb.2024.124269","DOIUrl":"10.1016/j.jchromb.2024.124269","url":null,"abstract":"<div><p>Polydrug use is a serious health and social problem worldwide. Over the past several years, there has been an increasing tendency to combine narcotics, alcohol, sedatives, and/or stimulants. To the traditional drugs of abuse and alcohol, an increase of new abuse drugs such as synthetic opioids has been added. In the current study, the development and validation of an innovative and fast analytical procedure has been presented to determine drugs of abuse, ethyl glucuronide and synthetics opioids in 30 mg of human hair through a single digestion, purification and analysis in LC-MS/MS. A combine simple preparation of hair sample followed to a single chromatographic run of 10 min has been proposed. A full validation for 54 target analytes for the parameters of selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, recovery, and dilution integrity was successful completed. The method was linear in different ranges with r values of at least 0.990; the value to the validated LLOQ values were in the range 0.1–100 pg/mg. The method offered satisfactory precisions (CV&lt;15 % and accuracy ± 20 %). In conclusion, a significant reduction in the overall times of the analytical procedure and the reduction of consumables costs make this method extremely advantageous and undoubtedly useful in routine laboratory workflow analyses and open the way to the prospect of a further implementation which also includes other classes of xenobiotics.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1246 ","pages":"Article 124269"},"PeriodicalIF":2.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1570023224002782/pdfft?md5=06e2af8082bc6dd42ec780d663896aff&pid=1-s2.0-S1570023224002782-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous determination of three tyrosine kinase inhibitors and three triazoles in human plasma by LC-MS/MS: applications to therapeutic drug monitoring and drug-drug interaction studies","authors":"Ninghong Li ,&nbsp;Lu Liu ,&nbsp;Dong Liu ,&nbsp;Hengyi Yu ,&nbsp;Guangjie Yang ,&nbsp;Lihui Qiu ,&nbsp;Yufei Chen ,&nbsp;Dong Xiang ,&nbsp;Xuepeng Gong","doi":"10.1016/j.jchromb.2024.124276","DOIUrl":"10.1016/j.jchromb.2024.124276","url":null,"abstract":"<div><p>Tyrosine kinase inhibitors (TKIs) and triazole antifungals are the first-line drugs for treating chronic myeloid leukemia (CML) and fungal infections, respectively, but both suffer from large exposure differences and narrow therapeutic windows. Moreover, these two types of drugs are commonly used together in CML patients with fungal infections. Multiple studies and guidelines have suggested the importance of therapeutic drug monitoring (TDM) of TKIs and triazoles. Currently, methods for the simultaneous determination of both types of drugs are limited. We developed a simple, rapid, and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of three commonly used TKIs (imatinib, dasatinib, and nilotinib) and three commonly used triazoles (voriconazole, itraconazole, and posaconazole) in human plasma. The analytes were eluted on a Welch XB-C₁₈ analytical column (50 × 2.1 mm, 5 µm) at 0.7 mL/min, using a gradient elution of 10 mM ammonium formate (A) and methanol–acetonitrile-isopropanol (80:10:10, <em>v</em>/<em>v</em>/<em>v</em>) containing 0.2 % formic acid (B) with a total analysis time of 3.5 min. The calibration curves were linear over the range from 20 to 4000 ng/mL for imatinib and nilotinib, from 2 to 400 ng/mL for dasatinib, and from 50 to 10,000 ng/mL for voriconazole, itraconazole, and posaconazole. Selectivity, accuracy, precision, recovery, matrix effect, and stability all met the validation requirements. The method was successfully used for TDM in CML patients who co-treated with both TKIs and triazoles. Drug-drug interaction analysis between TKIs and triazoles showed that a significant positive correlation was observed between imatinib and voriconazole, as well as dasatinib and voriconazole. Therefore, this method can be well applied in clinical TDM for patients receiving TKIs, triazoles, or both simultaneously.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1246 ","pages":"Article 124276"},"PeriodicalIF":2.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and simultaneous quantification of potential genotoxic impurities in first-line HIV drug dolutegravir sodium using fast ultrasonication-assisted extraction method coupled with GC–MS and in-silico toxicity assessment","authors":"Elumalai Sambandan ,&nbsp;Kathavarayan Thenmozhi ,&nbsp;G. Santosh ,&nbsp;Chun-Chi Wang ,&nbsp;Pei-Chien Tsai ,&nbsp;Swapnil Gurrani ,&nbsp;Sellappan Senthilkumar ,&nbsp;Yi-Hsun Chen ,&nbsp;Vinoth Kumar Ponnusamy","doi":"10.1016/j.jchromb.2024.124275","DOIUrl":"10.1016/j.jchromb.2024.124275","url":null,"abstract":"<div><p>Dolutegravir (DLG) has become a distinctive first-line antiretroviral therapy for the treatment of HIV in most countries due to its affordability, high efficacy, and low drug-drug interactions. However, the evaluation of genotoxic impurities (GTIs) in DLG and their toxicity assessment has not been explored thoroughly. Thus, in this study, a simple, fast, and selective analytical methodology was developed for the identification and determination of 7 GTIs in the comprehensive, explicit route of synthesis for the dolutegravir sodium (DLG-Na) drug. A facile, fast ultrasonication-assisted liquid–liquid extraction procedure was adapted to isolate the GTIs in DLG-Na and then analyzed using the gas chromatography (GC)-electron impact (EI)/mass spectrometer (MS) quantification (using selective ion monitoring mode) technique. This EI-GC/MS method was validated as per the current requirements of ICH Q2 (R1) guidelines. Under optimal method conditions, excellent linearities were achieved with R between 0.9959 and 0.9995, and high sensitivity was obtained in terms of detection limits (LOD) between 0.15 to 0.63 µg/g, and quantification limits (LOQ) between 0.45 to 1.66 µg/g for the seven GTIs in DLG. The obtained recoveries ranged from 98.2 to 104.3 % at LOQ, 15 µg/g, and 18 µg/g concentration levels (maximum daily dose of 100 mg). This developed and validated method is rapid, easy to adopt, specific, sensitive, and accurate in estimating the seven GTIs in a relatively complex sodium matrix of the DLG-Na drug moiety. As a method application, two different manufactured samples of DLG-Na drug substances were analyzed for the fate of the GTIs and drug safety for the intended dosage applications. Moreover, an <em>in-silico</em> QSAR toxicity prediction assessment was carried out to prove scientifically the potential GTI nature of each impurity from the alerting functional groups.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1245 ","pages":"Article 124275"},"PeriodicalIF":2.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}