Journal of Chromatography B最新文献

{"title":"A novel method for the component identification of human blood products: Mass spectrometric analysis of human fibrinogen digested after SDS-PAGE in-gel digestion","authors":"Haonan Wang ,&nbsp;Binbin Ke ,&nbsp;Wenxi Wang ,&nbsp;Jianghong Guo ,&nbsp;Wang Ying ,&nbsp;Shuangcheng Ma ,&nbsp;Hong Jiang","doi":"10.1016/j.jchromb.2023.123718","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123718","url":null,"abstract":"<div><p>Human fibrinogen, as a blood product of special origin, is relatively simple to prepare and purify. Therefore, completely isolating and removing the relevant impurity proteins is difficult. Further, which impurity protein components are present is not clear. In this study, human fibrinogen products from seven enterprises were collected from the market, and the presence of impurity proteins was confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Subsequently, the major 12 impurity proteins were identified and screened by in-gel enzymolysis mass spectrometry, and 7 major impurity proteins with different peptide coverage were identified by enzyme-linked immunosorbent assay, in agreement with the mass spectrometry results. The seven major impurity proteins included fibronectin, plasminogen, F-XIII, F-VIII, complement factor H, cystatin-A, and α-2-macroglobulin. The final test results were in the range of undetectable to 50.94 µg/mL, with correspondingly low levels of impurity proteins between different companies and a manageable risk. Moreover, we found that these impurity proteins existed in the form of polymers, which might also be an important cause of adverse reactions. This study established a protein identification technique applicable to fibrinogen products, which provided new ideas for studying the protein composition of blood products. In addition, it provided a new means of testing for companies to monitor the flow of proteomic fractions and improve the purification yield and product quality. It laid the foundation for reducing the risk of clinical adverse reactions.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1226 ","pages":"Article 123718"},"PeriodicalIF":3.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3205036","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 LC-MS/MS method for determination of clenbuterol enantiomers in animal tissues and its application to the enantioselective distribution in Bama mini-pigs","authors":"Jianli Zhang ,&nbsp;Jianghai Lu ,&nbsp;Yinong Zhang ,&nbsp;Yan Wang","doi":"10.1016/j.jchromb.2023.123790","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123790","url":null,"abstract":"<div><h3>Objectives</h3><p>To establish and validate a simple and reliable analytical method for separation and determination of clenbuterol enantiomers (<em>R</em>-(-)-clenbuterol &amp; <em>S</em>-(+)-clenbuterol) in animal tissues, and apply it to the enantioselective distribution of clenbuterol in Bama mini-pigs.</p></div><div><h3>Methods</h3><p>A LC-MS/MS analytical method was developed and validated in positive multiple reaction monitoring mode with electrospray ionization. After perchloric acid deproteinization, samples were pretreated only by one step liquid–liquid extraction using <em>tert</em>-butyl methyl ether under strong alkaline condition. Teicoplanin was used as chiral selector and 10 mM ammonium formate methanol solution was used as mobile phase. The optimized chromatographic separation conditions were completed in 8 min. Two chiral isomers in 11 edible tissues from Bama mini-pigs were investigated.</p></div><div><h3>Results</h3><p><em>R</em>-(-)-clenbuterol and <em>S</em>-(+)-clenbuterol can be baseline separated and accurately analyzed with a linear range of 5–500 ng/g. Accuracies ranged from −11.9–13.0% for <em>R</em>-(-)-clenbuterol and −10.2–13.2% for <em>S</em>-(+)-clenbuterol, intra-day and inter-day precisions were between 0.7 and 6.1% for <em>R</em>-(-)-clenbuterol and 1.6–5.9% for <em>S</em>-(+)-clenbuterol. <em>R/S</em> ratios in edible tissues of pigs were all significantly lower than 1.</p></div><div><h3>Conclusions</h3><p>The analytical method has good specificity and robustness in determination of <em>R</em>-(-)-clenbuterol and <em>S</em>-(+)-clenbuterol in animal tissues, and can be used as a routine analysis method for food safety and doping control. There is a significant difference in <em>R/S</em> ratio between pig feeding tissues and pharmaceutical preparations (racemate with <em>R/S</em> ratio of 1), which makes it possible to identify the source of clenbuterol in doping control and investigation.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1226 ","pages":"Article 123790"},"PeriodicalIF":3.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3205037","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 of anti-photoaging components of Olea europaea leaves based on spectrum-effect relationship","authors":"Fanghua Xu ,&nbsp;Xuetao Yi ,&nbsp;Xin Zhang ,&nbsp;Dong Pei ,&nbsp;Jiangjuan Yuan ,&nbsp;Ningli Wang ,&nbsp;Duolong Di ,&nbsp;Weidan Zeng ,&nbsp;Yun Liu ,&nbsp;Han Wang","doi":"10.1016/j.jchromb.2023.123807","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123807","url":null,"abstract":"<div><p>In this study, to identify bioactive components of <em>Olea europaea</em> leaves extract (OLE), chemometrics analyses including bivariate correlation analysis and partial least squares regression were used to establish the relationships between the chromatograms and anti-photoaging effect of OLE samples. Firstly, the fingerprint of olive leaves extract was determined by high-performance liquid chromatography (HPLC). Photoaging models of HaCaT cells were established by UVB irradiation. The photoaging resistance of OLE was evaluated by cell viability using the MTT assay. Chemometrics analyses showed that compounds 14, 19, 20, 24, 26, and 28 might be the major anti-photoaging components of OLE. Furthermore, after separation by HSCCC and NMR identification, compound 19 is luteoloside and compound 24 is oleuropein. Oleuropein and luteoloside were docked with collagenase (MMP-1), stromelysin (MMP-3), and gelatinase (MMP-9), respectively. The results showed that oleuropein and luteoloside inhibited their activity by directly interacting with MMP-1, MMP-3, and MMP-9, thereby exhibiting anti-photoaging activity. The current bioassay and spectrum-effect relationships are proper for associating sample quality with the active ingredient, and our finding would provide foundation and further understanding of the quality evaluation and quality control of <em>Olea europaea</em>.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1226 ","pages":"Article 123807"},"PeriodicalIF":3.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3205039","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":"High-throughput identification and determination of antifungal triazoles in human plasma using UPLC-QDa","authors":"Lulu Pan,&nbsp;Xiaxia Fan,&nbsp;Ao Jia,&nbsp;Yafei Li,&nbsp;Yidan Zhao,&nbsp;Ying Liu,&nbsp;Aifeng Wang,&nbsp;Yongcheng Ma","doi":"10.1016/j.jchromb.2023.123774","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123774","url":null,"abstract":"<div><p>Triazoles are common agents for invasive fungal infections, while therapeutic drug monitoring is needed to improve antifungal efficacy and reduce toxicity. This study aimed to exploit a simple and reliable liquid chromatography-mass spectrometry method for high-throughput monitoring of antifungal triazoles in human plasma using UPLC-QDa. Triazoles in plasma were separated by chromatography on a Waters BEH C18 column and detected using positive ions electrospray ionization fitted with single ion recording. M⁺ for fluconazole (<em>m</em>/<em>z</em> 307.11) and voriconazole (<em>m</em>/<em>z</em> 350.12), M²⁺ for posaconazole (<em>m</em>/<em>z</em> 351.17), itraconazole (<em>m</em>/<em>z</em> 353.13) and ketoconazole (<em>m</em>/<em>z</em> 266.08, IS) were selected as representative ions in single ion recording mode. The standard curves in plasma showed acceptable linearities over 1.25–40 μg/mL for fluconazole, 0.47–15 μg/mL for posaconazole and 0.39–12.5 μg/mL for voriconazole and itraconazole. The selectivity, specificity, accuracy, precision, recovery, matrix effect, and stability met acceptable practice standards under Food and Drug Administration method validation guidelines. This method was successfully applied to the therapeutic monitoring of triazoles in patients with invasive fungal infections, thereby guiding clinical medication.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1226 ","pages":"Article 123774"},"PeriodicalIF":3.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1560542","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":"Magnetic graphitized carbon black based on crystal growth method combined with high-resolution mass spectrometry for screening of 300 pesticide residues in Radix Codonopsis and Angelica sinensis","authors":"Hongyan Zhang ,&nbsp;Qiaoying Chang ,&nbsp;Fang Yang ,&nbsp;Jian Li ,&nbsp;Fuxiang Wu ,&nbsp;Ruobin Bai","doi":"10.1016/j.jchromb.2023.123788","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123788","url":null,"abstract":"<div><p>In this study, a high-throughput method for analyzing 300 pesticide residues in <em>Radix Codonopsis</em> and <em>Angelica sinensis</em> was established by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) using iron tetroxide loaded graphitized carbon black magnetic nanomaterial (GCB/Fe₃O₄) as the purification material. It was optimized that saturated salt water and 1 % acetate acetonitrile were used as the extraction solution, then the supernatant was purified with 2 g anhydrous CaCl₂ and 300 mg GCB/Fe₃O₄. As a result, 300 pesticides in <em>Radix Codonopsis</em> and 260 in <em>Angelica sinensis</em> achieved satisfactory results. The limits of quantification of 91 % and 84 % of the pesticides in <em>Radix Codonopsis</em> and <em>Angelica sinensis</em> reached 10 μg/kg, respectively. The matrix-matched standard curves ranging from 10 to 200 μg/kg were established with correlation coefficients (R) above 0.99. The pesticides meeting SANTE/12682/2021 accounted for 91.3 %, 98.3 %, 100.0 % and 83.8 %, 97.3, 100.0 % of the total pesticides added in <em>Radix Codonopsis</em> and <em>Angelica sinensis</em> respectively, which were spiked at 10, 20,100 μg/kg. The technique was applied to screen 20 batches of <em>Radix Codonopsis</em> and <em>Angelica sinensis</em>. Five pesticides were detected, three of which were prohibited according to the Chinese Pharmacopoeia (2020 Edition). The experimental results showed that GCB/Fe₃O₄ coupled with anhydrous CaCl₂ exhibited good adsorption performance and could be used for sample pretreatment of various pesticide residues in <em>Radix Codonopsis</em> and <em>Angelica sinensis</em>. Compared with the reported methods for determining pesticides in traditional Chinese medicine (TCM), the proposed method has the advantage of less time-consuming in the clean-up procedure. Furthermore, as a case study on root TCM, this approach may serve as a reference for other TCM.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1226 ","pages":"Article 123788"},"PeriodicalIF":3.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3082313","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":"Efficient separation of IgG from IgM antibodies via conjugated surfactant micelles","authors":"Thisara Jayawickrama Withanage ,&nbsp;Rami Krieger ,&nbsp;Ellen Wachtel ,&nbsp;Guy Patchornik","doi":"10.1016/j.jchromb.2023.123805","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123805","url":null,"abstract":"<div><p>Immunoglobulin-G (IgG) (∼150 kDa) antibodies confer longer term immunity against bacterial or viral infections than the heavier IgM’s (∼900 kDa), which are generally detectable in blood circulation in response to more recently acquired infections. There may be, however, a time overlap, which is problematic for diagnostic purposes, in the interests of which it is essential to separate IgM's from IgG’s. We describe a purification platform, functioning at pH 6.5, containing Tween-20, or Brij-O20, non-ionic detergent micelles, mixed with the sugar-rich detergent dodecyl maltoside (DDM), amino acid monomer tyrosine (Tyr), and conjugated by the amphiphilic complex [(bathophenanthroline)₃: Fe²⁺]. Using conjugated Brij-O20 micelles, with input molar ratio IgG: IgM 9:1, IgG is recovered at 10 °C with 85–90% yield, (by SDS-PAGE densitometry) and ≥95% purity (also by SDS-PAGE), while IgM's are recovered at lower yields (28–34%) and contain small amounts of co-extracted IgG's. Addition of <em>E. coli</em> lysate as an artificial contamination background does not reduce the yield or purity of the recovered IgG. Tween-20/DDM/Tyr micelles lead to IgG purity ≥95% similar to that of Brij-O20, but with lower process yields (64–70%, by densitometry). Chromatographic separation with Protein A or Protein G resins leads to yields comparable to those obtained with Brij-O20 micelles, but with lower purity.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1226 ","pages":"Article 123805"},"PeriodicalIF":3.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3082316","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":"Determination of thyroid hormones in lake sturgeon (Acipenser fulvescens) tissues at different developmental stages using a sensitive liquid chromatography-mass spectrometry method","authors":"Sonam Tamrakar ,&nbsp;Jacob G. Kimmel ,&nbsp;Yu-Wen Chung-Davidson ,&nbsp;Tyler J. Buchinger ,&nbsp;Kim T. Scribner ,&nbsp;Weiming Li","doi":"10.1016/j.jchromb.2023.123803","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123803","url":null,"abstract":"<div><p><span><span><span>Thyroid hormones (TH) are known to play an important role in the growth and development of vertebrates. In fish species, TH regulates the larval-juvenile metamorphosis, and is crucial for development during early life stages. Monitoring the variations in TH levels at different life stages can provide insights into the regulation of metamorphosis and fish development. In this study, we developed an extremely sensitive method for the quantification of </span>thyroxine (T4), </span>triiodothyronine (T3), and reverse-triiodothyronine (rT3), in lake sturgeon (</span><span><em>Acipenser</em><em> fulvescens</em></span><span><span>) tissues from eggs, free embryos, larvae, and juveniles. The target compounds were extracted by an enzymatic digestion method, followed by </span>protein precipitation<span>. Further cleanup was performed by liquid–liquid extraction (LLE) and solid phase extraction (SPE) using SampliQ OPT cartridges. The liquid-chromatography tandem mass spectrometry (LC-MS/MS) method used to quantify TH compounds showed remarkably high sensitivity with the limit of detection (LOD) and the limit of quantification (LOQ) ranging from &lt; 1 pg/mL to 10 pg/mL and linearity in the range of 10–50,000 pg/mL. This method was validated for tissue samples across several early developmental stages and was checked for intra- and inter-day accuracy (78.3−111.2 %) and precision (0.1−4.9 %), matrix effect (75.4−134.1 %), and recovery (41.2−69.0 %). The method was successfully applied for the quantification and comparison of T4, T3 and rT3 in hatchery raised lake sturgeon samples collected at unique time points (</span></span><em>i.e.,</em> days post fertilization dpf) including fertilized eggs (11 dpf), free embryos (14 dpf), larvae (22 dpf), juveniles (40 dpf) and older juveniles (74 dpf). With modifications, this method could be applied to other species important for agriculture or conservation.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1226 ","pages":"Article 123803"},"PeriodicalIF":3.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1698813","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":"Optimization of orthogonal separations for the analysis of oligonucleotides using 2D-LC","authors":"Christina Vanhinsbergh ,&nbsp;Elliot C. Hook ,&nbsp;Nicola Oxby ,&nbsp;Mark J. Dickman","doi":"10.1016/j.jchromb.2023.123812","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123812","url":null,"abstract":"<div><p>Oligonucleotides are commonly analysed using one dimensional chromatography (1D-LC) to resolve and characterise manufacturing impurities, structural isomers and (in respect to emerging oligonucleotide therapeutics) drug substance and drug product. Due to low selectivity and co-elution of closely related oligonucleotides using 1D-LC, analyte resolution is challenged. This leads to the requirement for improved analytical methods. Multidimensional chromatography has demonstrated utility in a range of applications as it increases peak capacity using orthogonal separations, however there are limited studies demonstrating the 2D-LC analysis of closely related oligonucleotides. In this study we optimised OGN size and sequence based separations using a variety of 1D-LC methods and coupled these orthogonal modes of chromatography within a 2D-LC workflow. Theoretical 2D-LC workflows were evaluated for optimal orthogonality using the minimum convex hull metric. The most orthogonal workflow identified in this study was ion-pair reversed phase using tributylammonium acetate (IP-RP-TBuAA) coupled with strong anion exchange in conjunction with sodium perchlorate (SAX-NaClO₄) at high mobile phase pH. We developed a heart-cut (IP-RP-TBuAA)-(SAX-NaClO₄) 2D-LC method for analysis of closely related size and sequence variant OGNs and OGN manufacturing impurities. The 2D-LC method resulted in an increased orthogonality and a reduction in co-elution (or close elution). Application of a UV based reference mapping strategy in conjunction with the 2D-LC method demonstrated a reduction in analytical complexity by reducing the reliance on mass based detection methods.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1227 ","pages":"Article 123812"},"PeriodicalIF":3.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3400369","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 device for swift and efficient CD44 protein digestion of pipette tips in human serum","authors":"Chandrababu Rejeeth ,&nbsp;Nipun Babu Varukattu ,&nbsp;Raju Suresh Kumar ,&nbsp;Abdulrahman I. Almansour ,&nbsp;Natarajan Arumugam","doi":"10.1016/j.jchromb.2023.123840","DOIUrl":"10.1016/j.jchromb.2023.123840","url":null,"abstract":"<div><p>For molecular diagnostics in modern biomedical research, electrospray ionisation mass spectrometry (ESI-MS) based on proteome profiling is important. Now a days, sample preparation such as proteolysis and protein extraction remain incredibly challenging and inefficient. Recent sample-preparation methods based on micro tips show promising results toward the aim “a proteome in an hour”. Proteolysis at the tip, is still infrequently observed and does not represent the processing of complex bio-samples. In this study, we outline a unique technique for detecting and extracting human serum CD44 biomarkers by ligand–protein interactions. This method employs macropores silica particles (MPSP) or (MOSF) modified with hyaluronic acid (HA). In order to assist in the profile of the human serum proteome, we limitations of immunoassays for rapid and multimodal proteolysis. For effective in situ proteolysis, in micropipette tips, MPSP were designed as nanoreactors with variable pore size and surface chemistry. In MS-based bottom-up proteome analysis, the device as-built demonstrated favourable sensitivity (LOD of 0.304 ± 0.007 ng/mL and LOQ of 0.973 ± 0.054 ng/mL), selectivity, durability (at −20 °C for 2 months), reuse (at least 10 times), and minimal memory impact. In addition, we examined into specific surface chemistries of nanoparticles for the absorption of proteins in serum and profiled the HA-binding serum proteome, setting a new preliminary benchmark for future databases. Our study not only helped establish a new platform for extracting/detection of CD44 and identifying the HA-binding proteome, but it also offered design recommendations for ligand affinity-based techniques for the antibody-free study of serum biomarkers with a view towards diagnostic applications.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1227 ","pages":"Article 123840"},"PeriodicalIF":3.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10094881","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":"Determination of lekethromycin in plasma and tissues of pneumonia-infected rats by ultra-high performance liquid chromatography-tandem mass spectrometry","authors":"Yuying Cao ,&nbsp;Pan Sun ,&nbsp;Jicheng Qiu ,&nbsp;Jingyuan Kong ,&nbsp;Yuxin Yang ,&nbsp;Yu Liu ,&nbsp;Degang Zhou ,&nbsp;Jianzhong Wang ,&nbsp;Xingyuan Cao","doi":"10.1016/j.jchromb.2023.123811","DOIUrl":"https://doi.org/10.1016/j.jchromb.2023.123811","url":null,"abstract":"<div><p><span><span><span>Lekethromycin (LKMS), a novel semi-synthetic macrolide </span>lactone<span><span>, had the characteristics of high plasma protein binding rate, fast absorption, slow elimination, and wide distribution in rat </span>pharmacokinetics<span> studies. A reliable analytical ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based method was established by using tulathromycin and TLM (CP-60, 300) as internal standards for detection of LKMS and LKMS-HA, respectively. Samples preparation and UPLC-MS/MS conditions were optimized for complete and accurate quantification. Tissue samples were extracted with 1% formic acid<span> in acetonitrile and purified by PCX cartridges. According to FDA and EMA guidelines for </span></span></span></span>bioanalytical method, several rat characteristic tissues were selected for method validation, such as muscle, lung, spleen, liver, kidney, and intestines. The transitions </span><em>m</em>/<em>z</em> 402.900 &gt; 158.300, <em>m</em>/<em>z</em> 577.372 &gt; 158.309, <em>m</em>/<em>z</em> 404.200 &gt; 158.200, and <em>m</em>/<em>z</em> 577.372 &gt; 116.253 were monitored and quantified for LKMS, LKMS-HA, tulathromycin and TLM, respectively. According to the ratio with IS peak aera, the accuracy and precision of LKMS were 84.31%-112.50% with RSD 0.93%-9.79% and LKMS-HA were 84.62%-103.96% with RSD 0.73%-10.69%, and the method had been established and complied with FDA, EU, and Japanese guidelines. Finally, this method was applied to detect LKMS and LKMS-HA in plasma and tissues of pneumonia-infected rats that were intramuscularly administered and treated with LKMS intramuscular injection of 5 mg/kg BW and 10 mg/kg BW, and the characteristics of pharmacokinetics and tissue distribution were compared with normal rats.</p></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1227 ","pages":"Article 123811"},"PeriodicalIF":3.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1698812","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}