Journal of Chromatography B最新文献

{"title":"Identification of flavonoid isomers in Scutellaria baicalensis using QSRR modeling","authors":"Changhai Sun ,&nbsp;Mengxin Xiao ,&nbsp;Biyue Cui ,&nbsp;Liting Mu ,&nbsp;Shuting Zhang ,&nbsp;Xinran Zhang ,&nbsp;Shushuang Shen","doi":"10.1016/j.jchromb.2025.124491","DOIUrl":"10.1016/j.jchromb.2025.124491","url":null,"abstract":"<div><div>In the current research on Scutellaria baicalensis, a substantial number of flavonoid isomers were identified. Given the limitations of existing analytical methods to accurately identify these isomers, the present study was conducted to determine the flavonoid isomers in Scutellaria baicalensis by combining the mass spectrometry database and stepwise multiple linear regression QSRR model of flavonoids established by the research group in the previous phase. The UHPLC-Q-Exactive Orbitrap-MS technique with isocratic elution injection was employed, and compositional analysis of Scutellaria baicalensis was conducted utilizing the mass spectrometry database to identify two groups of flavonoids and their isomers. The QSRR model was calibrated using standards, and the two groups of flavonoids and their isomers in Scutellaria baicalensis were distinguished and identified utilizing the QSRR model and calibration equation. In this investigation, two groups of flavonoids and their isomers in Scutellaria baicalensis were successfully identified and differentiated. The findings suggest that this QSRR model can be utilized to identify flavonoid isomers, providing a viable method for differentiating isomers of chemical components.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1254 ","pages":"Article 124491"},"PeriodicalIF":2.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350623","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 aptamer-based probe for the identification and enrichment of trophoblast cells","authors":"Mang Gui ,&nbsp;Weiwei Xu ,&nbsp;Yueyue Gui ,&nbsp;Chenyun Zhang ,&nbsp;Dandan Shi ,&nbsp;Jiehua Ma ,&nbsp;Jin Qiu","doi":"10.1016/j.jchromb.2025.124479","DOIUrl":"10.1016/j.jchromb.2025.124479","url":null,"abstract":"<div><div>Trophoblast cells, which are shed into the maternal reproductive tract, are emerging as a valuable source for prenatal diagnostic cells. However, the current enrichment efficiency of these cells is inadequate for clinical purposes. The reliance on antibody-based cell recognition methods has been a significant barrier to developing more effective enrichment techniques. In our research, we employed systematic evolution of ligands by exponential enrichment (SELEX) technology to identify three aptamers that can specifically bind to the HLA-G protein, a unique marker on the surface of trophoblast cells. Through a process of meticulous truncation and optimization, we successfully developed the highly effective nucleic acid aptamer H4–2. Utilizing H4–2, we engineered a novel circulating microfluidic system that achieves an impressive 65 % enrichment efficiency for trophoblast cells. This advancement holds substantial promise for enhancing prenatal diagnostic methods that rely on intact foetal cells.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1253 ","pages":"Article 124479"},"PeriodicalIF":2.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143168928","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":"An ultra-sensitive liquid chromatography tandem mass spectrometry method for the simultaneous quantification of 2H6-alectinib and alectinib in human plasma to support a microtracer food-effect trial","authors":"L.T. van der Heijden ,&nbsp;M.M. Tibben ,&nbsp;M.I. Mohmaed Ali ,&nbsp;L.G.J. Aardenburg ,&nbsp;N. Steeghs ,&nbsp;J.H. Beijnen ,&nbsp;H. Rosing ,&nbsp;A.D.R. Huitema","doi":"10.1016/j.jchromb.2025.124488","DOIUrl":"10.1016/j.jchromb.2025.124488","url":null,"abstract":"<div><div>A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of ²H₆-alectinib and alectinib was developed and validated for the support of a pilot microtracer food-effect trial. The aim of the bioanalytical method was the simultaneous quantification of low ²H₆-alectinib concentrations and high alectinib concentrations that are present in study samples, using a single sample pre-treatment and analysis method. Sample preparation consisted of liquid-liquid extraction with tert-butyl methyl ether (TBME). The final extract was injected on a C18 column (1.7 μm particles, 50 × 2.1 mm ID) with gradient elution. A triple quadruple mass spectrometer operating in positive method was used for detection and quantification. The validated concentration ranges were from 5 to 400 pg/mL for ²H₆-alectinib and from 25 to 2000 ng/mL for alectinib. The bias was within ±3.5 % and ± 5.1 % and precisions ≤5.7 % and ≤ 1.9 % for ²H₆-alectinib and alectinib, respectively. By correcting for the interference of natural abundant isotopes of alectinib, ²H₆-alectinib plasma concentrations between 1 and 5 pg/mL could be quantified, with bias was within ±15.9 % and precision ≤12.5 % in the presence of 400 ng/mL or 800 ng/mL alectinib. The clinical application was successfully applied to quantify ²H₆-alectinib and alectinib in plasma samples from a participant enrolled in a microtracer food-effect study.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1253 ","pages":"Article 124488"},"PeriodicalIF":2.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143168929","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":"Detection and application of 40 piperazine compounds in hair suitable for rapid separation of isomers","authors":"Jinting Liu ,&nbsp;Xin Wang ,&nbsp;Wanting Xie ,&nbsp;Liying Zhou ,&nbsp;Lina Pei ,&nbsp;Shuo Yang ,&nbsp;Guoqing Gao ,&nbsp;Keming Yun ,&nbsp;Yan Shi","doi":"10.1016/j.jchromb.2025.124473","DOIUrl":"10.1016/j.jchromb.2025.124473","url":null,"abstract":"<div><div>A simple and sensitive procedure, using benzylpiperazine-D₇ (BZP-D₇) as an internal standard, has been developed and validated for the qualitative and quantitative analysis of 40 piperazines in hair. Drugs were extracted from 20 mg of hair with 0.5 mL of methanol containing 1 ng/mL BZP-D₇. After ultrasonication, centrifugation and filtration, the supernatant was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) operating in the multiple reaction monitoring mode. Piperazine-type substances were separated in 10 min on a T₃ column using a mobile phase gradient composed of A (water, formic acid 0.1 %, acetonitrile 5 %, and 20 mmol/L ammonium acetate) and B (acetonitrile). The developed and validated method showed good selectivity, sensitivity (limit of detection: 0.5–20 pg/mg and lower limit of quantitation: 5–20 pg/mg), linearity (R² &gt; 0.99), accuracy, precision, and dilution integrity. The method also showed good recovery and acceptable matrix effects for most of the targeted compounds. This analytical approach was successfully applied for the identification and quantification of piperazine-type substances in hair from rat and guinea pig.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1253 ","pages":"Article 124473"},"PeriodicalIF":2.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073093","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":"Interpretation of negative-ion chemical ionization GC–MS and GC–MS/MS mass spectra of perfluorinated organic analyte derivatives: Consideration of reduction reactions in the gas phase","authors":"Dimitrios Tsikas","doi":"10.1016/j.jchromb.2025.124487","DOIUrl":"10.1016/j.jchromb.2025.124487","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The main priniciples of gas chromatography–mass spectrometry (GC–MS) and gas chromatography-tandem mass spectrometry (GC–MS/MS) are: 1) separation of mostly derivatized analytes in the lumen of temperature-programmed gas chromatography (GC) fused-silica capillary columns, 2) ionization of gaseous charge-free analyte derivatives in the ion-source by means of electrons (electron ionization, EI) or in combination with a reagent gas such as methane (chemical ionization, CI), and 3) separation of simply ionized analytes or fragments in electric and/or magnetic fields due to their mass-to-charge ratio (&lt;em&gt;m/z&lt;/em&gt;). EI generates (radical) cations, whereas CI is used to analyze either simply positively (positive-ion chemical ionization, PICI) or simply negatively charged analytes (negative-ion chemical ionization, NICI). In general, NICI in combination with the use of fluorinated (F) derivatization reagents is used in quantitative analyses as fluorinated analytes are softly ionized thus producing anions in high abundance and of high intensity. In quantitative analyses by GC-NICI-MS and GC-NICI-MS/MS, the position of the negative charge in the detected anions is secondary and in many cases unknown. The question of the position of the negative charge in analyte anions formed by NICI in GC-MS and GC-MS/MS is basically of theoretical interest and poorly addresed. The present article discusses this issue in detail. Previously reported GC-NICI-MS and GC-NICI-MS/MS quantitative methods for different classes of analytes, such as amino acids, fatty acids and drugs alongside their &lt;sup&gt;2&lt;/sup&gt;H-, &lt;sup&gt;13&lt;/sup&gt;C-, &lt;sup&gt;15&lt;/sup&gt;N- and &lt;sup&gt;18&lt;/sup&gt;O-isotopologs, after derivatization with fluorinated reagents including pentafluorobenzyl bromide (PFB-Br), pentafluorobenzoyl chloride (PFB-COCl) and pentafluoropropionic anhydride (PFPA) serve as examples and resources of data. ChemDraw Professional software was used to construct chemical structures of analytes and ions found in GC-NICI-MS and GC-NICI-MS/MS mass spectra. The results of the present study provide unique insights into the gas-phase reactions that take place in the ion-source of GC-MS and in the collision-chamber of GC-MS/MS instruments mainly based on the quadrupole (Q) technology. Paradoxically, the negative charge cannot be always assigned in precursor and product ions by standard rules of chemistry, unlike in EI and PICI. For example, PFB esters of fatty acids and eicosanoids (R-COO-PFB) ionize to form their carboxylates with the negative charge being definetly located in the carboxylic groups (R-COO&lt;sup&gt;−&lt;/sup&gt;, [M-PFB]&lt;sup&gt;−&lt;/sup&gt;). In contrast, methyl ester pentafluoropropionyl derivatives of amino acids ionize readily and abundantly under NICI conditions, yet the negative charge cannot be always asigned with apodictic certainty, even not for the calibrating/tuning compound perfluorotributylamine (PFTBA). The &lt;em&gt;paradox&lt;/em&gt; vanishes when considering gas-phase reactions in the ion-source ","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1253 ","pages":"Article 124487"},"PeriodicalIF":2.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073094","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":"Anion exchange chromatography coupled to mass spectrometry for deciphering the complexity of a highly glycosylated fusion protein (“protein HGF”)","authors":"Florian Füssl ,&nbsp;Keith Coleman ,&nbsp;Jonathan Bones","doi":"10.1016/j.jchromb.2025.124484","DOIUrl":"10.1016/j.jchromb.2025.124484","url":null,"abstract":"<div><div>Fc-fusion proteins are medicines developed for the treatment of complex diseases which feature enhanced pharmacokinetic properties compared to other therapeutic protein formats. A commonly used strategy for the extension of protein half-life in circulation is the introduction of negative charges on the protein, preferably through N- and O-glycans equipped with negatively charged sialic acid moieties. While enhancing pharmacokinetics, the presence of many glycosylation sites can coincide with a considerable protein heterogeneity, which renders analytical characterisation increasingly difficult. In this work, we demonstrate that the complexity of a highly glycosylated intact Fc-fusion protein can be well resolved using mass spectrometry (MS)-friendly anion exchange chromatography (AEX) with pH gradient elution. The application of the developed method allowed for the separation of 9 clear chromatographic peaks and the acquisition of high-quality protein spectra and thus, MS detection of intact protein isoforms. The resulting data enabled the identification of 268 protein features which represents a ∼ 25-fold increase in detected forms compared to output that could be obtained by simple size exclusion chromatography-mass spectrometry. The underlying cause for the separation selectivity observed in AEX was found to be differential protein sialylation while varying numbers of hexose and <em>N</em>-acetylglucosamine units on glycans were identified as other major contributors to the high heterogeneity observed.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1254 ","pages":"Article 124484"},"PeriodicalIF":2.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143272981","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":"A novel range-divided data dependent acquisition strategy for screening of diterpenoid alkaloids in Aconitum pendulum roots","authors":"Mei Deng ,&nbsp;Bishi Ren ,&nbsp;Jiayi Yi ,&nbsp;Hui Ding ,&nbsp;Hua Wang","doi":"10.1016/j.jchromb.2025.124486","DOIUrl":"10.1016/j.jchromb.2025.124486","url":null,"abstract":"<div><div>A novel range-divided data dependent acquisition (DDA) strategy was proposed for the screening of diterpenoid alkaloids in <em>Aconitum pendulum</em> roots. In range-divided DDA, the low-range was set between <em>m</em>/<em>z</em> 340–500 and the high-range was set between m/z 500–700 according to the molecular weight range of the diterpenoid alkaloids. The combined identification approach including MS¹ molecular weight, MS² spectrum interpretation, literature comparison, and standard verification was applied to the results. The range-divided DDA identified 15 more diterpenoid alkaloids than the full-range DDA under the same LC conditions. A total of 47 diterpenoid alkaloids were identified. Among them, brachyaconitines A-D were screened for the first time in <em>Aconitum pendulum</em>. This screening strategy can serve as a powerful tool for the discovery of novel metabolites in the field of plant metabolomics.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1253 ","pages":"Article 124486"},"PeriodicalIF":2.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073121","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":"Interaction study between HIV protease inhibitors and alectinib in rats based on an ultra-performance liquid chromatography tandem mass spectrometry method","authors":"Yizhang Chen ,&nbsp;Ziye Zhou ,&nbsp;Yuhan Zeng ,&nbsp;Zhongjiang Ye ,&nbsp;Rongqi Li ,&nbsp;Chuang Chen ,&nbsp;Jianhui Yang ,&nbsp;Jing Fu ,&nbsp;Tao Zhou ,&nbsp;Danna Jiang ,&nbsp;Sunting Qin ,&nbsp;Xiuhua Zhang ,&nbsp;Chenxiang Wang","doi":"10.1016/j.jchromb.2025.124483","DOIUrl":"10.1016/j.jchromb.2025.124483","url":null,"abstract":"<div><div>We established an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to measure alectinib concentrations in rat plasma and use it to investigate the effect of HIV protease inhibitors on the pharmacokinetic parameters of alectinib in rats. Acetonitrile was used to precipitate the samples. We used a BEH C18 column to perform chromatographic separation on a UPLC system. The mobile phase comprised 0.1 % formic acid, water, and acetonitrile. Mass spectrometry analysis was conducted using a Xevo TQ-Striple quadrupole tandem mass spectrometer. Alectinib and lorlatinib (internal standard) were measured in MRM mode. The fragment ions were 483.2-396.1 for alectinib and <em>m</em>/<em>z</em> 407.3-228.1 for lorlatinib. The validated UPLC-MS/MS method was used to study drug interactions of atazanavir, darunavir, indinavir, and ritonavir with alectinib in rat plasma. We found atazanavir, darunavir, indinavir, and ritonavir significantly inhibited alectinib metabolism. When administered with atazanavir, darunavir, indinavir, and ritonavir, the AUC_0-t of alectinib increased by 94.0 %, 175.7 %, 220.9 %, and 62.4 %, respectively; the clearance of alectinib decreased by 53.4 %, 63.6 %, 67.8 %, and 41.1 %, respectively. In short, we developed an UPLC-MS/MS approach to measure alectinib in rat plasma. Atazanavir, darunavir, indinavir, and ritonavir dramatically inhibited alectinib metabolism. The dosages should be adjusted when using atazanavir, darunavir, indinavir, and ritonavir with alectinib. Real-time monitoring should occur during treatment.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1253 ","pages":"Article 124483"},"PeriodicalIF":2.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078302","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":"Analytical and clinical validation of a volumetric absorptive microsampling (VAMS) – Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of Clofazimine in whole blood","authors":"Rhea Veda Nugraha ,&nbsp;Vycke Yunivita ,&nbsp;Prayudi Santoso ,&nbsp;Aliya Nur Hasanah ,&nbsp;Triana Nurul Meirina ,&nbsp;Atu Purnama Dewi ,&nbsp;Harold Eka Atmaja ,&nbsp;Lindsey te Brake ,&nbsp;Rob E. Aarnoutse ,&nbsp;Rovina Ruslami","doi":"10.1016/j.jchromb.2025.124482","DOIUrl":"10.1016/j.jchromb.2025.124482","url":null,"abstract":"<div><div>Monitoring clofazimine blood concentrations is crucial for preventing treatment failure in patients with Multidrug-resistant Tuberculosis (MDR-TB). Volumetric Absorptive Microsampling (VAMS) offers a practical alternative to Conventional Venous Sampling (CVS), enabling remote sampling. Samples collected via VAMS can be conveniently transported to laboratories via courier, enhancing accessibility and patient compliance. In this study, we developed and validated an analytical method for quantifying clofazimine in whole blood collected using VAMS. The study compared the performance and cost-effectiveness of VAMS with CVS. A total of 55 matched finger-prick VAMS and CVS samples were obtained from 39 MDR-TB patients and analyzed using validated UPLC-MS/MS assays. Clofazimine concentrations collected via VAMS and CVS were compared using Passing-Bablok regression, while bias and overall agreement were evaluated through Bland-Altman analysis. Passing-Bablok regression revealed no significant constant difference between VAMS and CVS (95% CI slope: 0.7627–0.9573; 95% CI intercept: −0.02141–0.06482), but systematic difference of 13% lower clofazimine concentrations was observed in VAMS compared to plasma. Bland-Altman analysis demonstrated moderate agreement, with mean plasma/VAMS ratio of 0.9457 (95% CI: 0.88358–1.00775) and 95% Limits of Agreement (LoA) ranging from 0.4956 (95% CI: 0.38881–0.60230) to 1.3858 (95% CI: 1.28903–1.50252). Although statistically significant bias was identified, applying correction factors could improve interchangeability between the two techniques. Furthermore, VAMS was more cost-effective than CVS, with approximate cost difference of 4.45 USD per sample. These findings suggest that VAMS sampling has the potential to replace CVS for routine clinical monitoring of clofazimine, offering a more accessible and economical approach.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1253 ","pages":"Article 124482"},"PeriodicalIF":2.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121916","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":"Experimental and computational analysis of lipophilicity and plasma protein binding properties of potent tacrine based cholinesterase inhibitors","authors":"Sandra Šegan ,&nbsp;Mirjana Mosić ,&nbsp;Vladimir Šukalović ,&nbsp;Ivana Jevtić","doi":"10.1016/j.jchromb.2025.124481","DOIUrl":"10.1016/j.jchromb.2025.124481","url":null,"abstract":"<div><div>The lipophilicity of thirteen tacrine/piperidine-4-carboxamide derivatives was assessed using reversed-phase thin-layer chromatography (RP-TLC) with MeOH and acetonitrile (ACN) as organic modifiers. Among the parameters evaluated, the R_M⁰ and C⁰ values obtained using MeOH were identified as the most reliable for characterizing the lipophilicity of the investigated compounds. The observed differences in lipophilicity among the derivatives resulted from a delicate interplay of substituent effects (hydrophobicity, polarity, steric hindrance, and electronic effects), positional influence, and characteristics of the organic modifier.</div><div>The plasma protein-binding (PPB) properties of the tacrine derivatives were analyzed using an HPLC method with a human serum albumin (HSA) stationary phase and a mobile phase composed of phosphate buffer (pH = 7) and 2-propanol. The experimental %PPB values calculated using from two experiments ranged from 82.38 % to 94.54 %, and 84.29 % to 98.16 % suggesting that most compounds bind efficiently but not excessively to plasma proteins.</div><div>Docking analysis revealed that all investigated ligands bind to Sudlow site I within HSA, which is the main binding site for heterocyclic aromatic compounds such as warfarine, azoprazone and tacrine. The key binding interactions are primarily hydrogen bonding and aromatic interactions.</div><div>Principal component analysis (PCA), conducted on both experimentally determined and predicted lipophilicity values, as well as on predicted adsorption and experimentally and predicted distribution data, underscored the significant role of lipophilicity in influencing adsorption and distribution processes.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1253 ","pages":"Article 124481"},"PeriodicalIF":2.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063037","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}