Journal of Pharmaceutical and Biomedical Analysis Open最新文献

{"title":"Development and validation of UHPLC-ESI-MS/MS bioanalytical method, ADMET profiling, and pharmacokinetic study of bioactive phytoconstituents from Ayurvedic botanical Guduchi (Tinospora cordifolia)","authors":"Aboli Girme,&nbsp;Vijay Parmar,&nbsp;Shubham Jagtap,&nbsp;Ganesh Saste,&nbsp;Siddharth J. Modi,&nbsp;Lal Hingorani","doi":"10.1016/j.jpbao.2023.100018","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100018","url":null,"abstract":"<div><p><em>Tinospora cordifolia</em> (TC) is known for its immense therapeutic applications in 'Ayurveda', which has created considerable scientific interest in pharmacology. Thus, a targeted and rapid bioanalytical UHPLC-ESI-MS/MS method was developed and validated for the extraction of its bioactive markers from diverse classes of diterpenes as tinosporide (TC1) and phytosterol-20-β-hydroxyecdysone (TC2) and isoquinoline alkaloids-jatrorrhizine (TC3), tetrahydropalmatine (TC4) from the TC stem extract (TCE) in rat plasma by solid phase extraction technique (SPE). The optimum recovery (≥ 90 %) was achieved for TC1–4 and internal standard fluoxymesterone (IS) with the SPE method on the C18 phase. The analytes were subjected to chromatographic analysis on the Agilent C18 Zorbax Eclipse Plus column (4.6 × 100 mm, 3.5 µ) with a gradient program using 0.1 % acetic acid in water (% <em>v/v</em>) and acetonitrile as mobile phase at a flow rate of 0.500 mL/min. The MS/MS quantification and validation were performed on the Shimadzu 8045 tandem mass spectrometer associated with the heated-ESI probe in SRM mode. The precursor to product ion transitions <em>m/z</em> 416.20→375.10 (TC1), 481.40→445.20 (TC2), 339.15→323.05 (TC3), 356.25→192.10 (TC4) and 337.20→91.00 (IS) were used for quantification. Also, <em>in silico</em> ADMET prediction and <em>in vivo</em> pharmacokinetics revealed that TC1–4 was well absorbed from the GI tract and could act as a P-GP substrate. In the pharmacokinetic study<em>,</em> TC1–4 could be detected by this validated bioanalytical method. The TC1 was found bioavailable, having an optimum half-life of &gt; 9.0 h to exhibit therapeutic activity with other TC bioactive markers <em>in vivo</em>. This research is the first comprehensive study on <em>in silico</em> and <em>in vivo</em> pharmacokinetics of TC biomarkers, which may aid in further pre-clinical and clinical trial investigations.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49879899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and application of a supercritical fluid chromatography-tandem mass spectrometry method for the simultaneous determination of pantoprazole enantiomers in rat plasma","authors":"Junli Lin ,&nbsp;Youchen Liu ,&nbsp;Jiawei Zhang ,&nbsp;Ziqi Lu ,&nbsp;Jianmin Guo ,&nbsp;Yuankeng Huang ,&nbsp;Baoqin Lin ,&nbsp;Wei Yang","doi":"10.1016/j.jpbao.2023.100016","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100016","url":null,"abstract":"<div><p>The study aimed to develop a supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method for the enantioselective separation and quantification of pantoprazole in rat plasma. The method utilized protein precipitation with acetonitrile to prepare plasma samples. SFC was performed on an Acquity ultra-performance convergence chromatography (UPCC) system. An Acquity UPCC Trefoil™ CEL2 column was employed for enantioseparation, and isocratic elution was achieved using a mobile phase consisting of CO₂-methanol (81:19, v/v). The detection of pantoprazole enantiomers and the internal standard phenacetin was carried out using a Xevo TQD triple quadrupole mass spectrometer in selected reaction monitoring mode with positive electrospray ionization. The developed method successfully achieved full separation of <em>S</em>- and <em>R</em>-pantoprazole enantiomers. Calibration curves were linear in the concentration range of 10–5000 ng/mL for both <em>S</em>- and <em>R</em>-pantoprazole. The method met the acceptance criteria for carry-over, accuracy, precision, extraction recovery, matrix effect, stability, and dilution integrity, demonstrating its stereoselectivity, sensitivity, accuracy, precision, and reliability. The validated method was then applied to investigate the toxicokinetics of racemic pantoprazole and evaluate the potential of chiral inversion between <em>S</em>- and <em>R</em>-pantoprazole in rats. Following oral administration of 200 mg/kg racemic pantoprazole once daily for 90 consecutive days, there was no significant difference in toxicokinetic parameters between the two enantiomers on both day 1 (single-dose experiment) and day 90 (multiple-dose experiment). This suggests that there is no enantioselectivity in the toxicokinetic behaviors of racemic pantoprazole in rat plasma. Additionally, bidirectional chiral inversion between <em>S</em>- and <em>R</em>-pantoprazole in plasma was observed after single-dose and multiple-dose oral administrations of <em>S</em>-pantoprazole (20, 100, and 200 mg/kg) or <em>R</em>-pantoprazole (200 mg/kg) to rats. Compared to single and low doses, there was no accumulation of each enantiomer in rat plasma following repeated and escalated dosing. Overall, this study provided the first report on the toxicokinetics of pantoprazole in rat plasma and presented the first SFC-MS/MS method for the simultaneous quantification of pantoprazole enantiomers in rat plasma.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100016"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49879895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach to determine residual aldehyde content in conjugated polysaccharides with 3-methyl-2-benzothiazolinonehydrazon (MBTH) by colorimetric method, automation, and HP-SEC","authors":"Weidong Tong,&nbsp;Mingxiang Lin,&nbsp;Ping Zhuang,&nbsp;Bukuru Anaclet,&nbsp;Castle Cooper","doi":"10.1016/j.jpbao.2023.100022","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100022","url":null,"abstract":"<div><p>Polysaccharide activation by periodate oxidation to form aldehydes, followed by conjugation with proteins via reductive amination is a general procedure to make polysaccharide-protein conjugate vaccines. Controlling the level of residue aldehyde content after conjugation is critical to ensure vaccine product stability. Herein, to support conjugation process optimization, we developed a 3-methyl-2-benzothiazolone hydrazone (MBTH) chemistry-based colorimetric method, which can measure low-level residual aldehyde polysaccharide-protein conjugate in high throughput 96-well plate format. This mechanism of detection works in two steps. First, MBTH reacts with the aldehyde group to form azine. Then the excess MBTH was oxidized by ferric ammonium sulfate in sulfamic acid to form a reactive cation, which reacts further with azine to form formazan, a characteristic blue chromophore at 610 nm, for colorimetric detection. The method performance, including detection limit, linearity range, matrix effect, kinetics, and color stability was systematically studied. For samples with severe matrix interference, a supplemental size exclusion chromatography (SEC) method was also developed as an alternative method.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100022"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X23000221/pdfft?md5=eafa9469ba2f3683e089c099514af195&pid=1-s2.0-S2949771X23000221-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136968400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a LC–MS/MS analytical method of 15 compounds related to renal function for a prognostic method of progression risk in patients with diabetic kidney disease","authors":"Ryota Kujirai ,&nbsp;Yotaro Matsumoto ,&nbsp;Mizuki Abe ,&nbsp;Kodai Hiramoto ,&nbsp;Takumi Watanabe ,&nbsp;Chitose Suzuki ,&nbsp;Takafumi Toyohara ,&nbsp;Takaaki Abe ,&nbsp;Yoshihisa Tomioka","doi":"10.1016/j.jpbao.2023.100021","DOIUrl":"10.1016/j.jpbao.2023.100021","url":null,"abstract":"<div><p>Diabetic kidney disease (DKD) onset and progression is a major cause of end-stage renal failure in diabetic patients, however, no practical method has been reported to predict the progression rate of renal function decline. Nine serum compounds are reported to associate with prognosis in type 1 diabetes patients; however, quantitative analytical methods for these compounds lacks. Herein, we developed a simultaneous quantitative method for 15 compounds, including Niewczas’s nine biomarker candidates, associated with renal function and its prognosis in kidney disease patients to achieve a prognostic method of renal function decline in DKD patients. This report describes the development and validation of a LC–MS/MS analytical method for 15 compounds of biomarker candidates using human plasma, serum, and urine as sample matrices. The analytes are N-acetyl-L-alanine, N6-acetyl-L-lysine, N-acetyl-L-serine, N-acetyl-L-threonine, phenyl sulfate, pseudouridine, N6-threonylcarbamoyladenosine, tryptophan 2-C-mannoside, tyrosine O-sulfate, creatinine, p-cresol sulfate, 4-ethylphenyl sulfate, indoxyl sulfate, N1-methyladenosine, and trimethylamine N-oxide. The Capcell Pak ADME-HR column was compared to several general columns and selected as the most suitable column for the simultaneous analysis of all 15 compounds. The proposed method was validated for selectivity, accuracy, precision, stability, dilution integrity, and parallelism. This report describes the suitability of the calibration ranges established and the actual sample concentrations of serum and urine from type 2 diabetic patients, as well as new findings on the unknown analyte levels of several compounds in these samples. The proposed method can be used to aid the development of prognostic methods for renal function decline in patients with DKD.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100021"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949771X2300021X/pdfft?md5=f0b7f3218761bed3d45465c43370fd8d&pid=1-s2.0-S2949771X2300021X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135371227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of impurities in cocoa shell powder using NIR spectroscopy","authors":"Marciano M. Oliveira ,&nbsp;Marcus V.S. Ferreira ,&nbsp;Mohammed Kamruzzaman ,&nbsp;Douglas F. Barbin","doi":"10.1016/j.jpbao.2023.100015","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100015","url":null,"abstract":"<div><p>Cocoa shell is a by-product from cocoa industry which contains bioactive compounds of high and attractive value for food, pharmaceutical and cosmetics industry. However, cocoa shell can be contaminated by undesirable materials that, even in small amounts, would not change the color, aroma, and taste characteristics of the final product. Identification and prediction of this impurity are performed using expensive methods that require chemicals and produce residues. Thus, this work aims to investigate the performances of benchtop (867–2535 nm) and portable (900–1700 nm) near-infrared (NIR) spectrometer for fast prediction of cocoa shell powder impurities. Mixtures (n = 432) of cocoa shell powders with leaves, pods, stem fragments and nibs at several proportions (0–20 % w/w), were analyzed. Multivariate calibration models were developed using partial least-squares regression (PLSR) with raw spectra and various preprocessing approaches applied to the spectra. The most informative spectral variables were selected by variable importance in projection (VIP) method. Results obtained for the benchtop (R²_P&gt; 0.99 and RMSEP&lt;0.71) and low-cost portable (R²_P&gt; 0.92 and RMSEP&lt;1.70) devices are promising, and portable spectrometer could be used to certify cocoa shell purity.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49879894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in surface plasmon resonance biosensors for medical diagnostics: An overview of recent developments and techniques","authors":"G.I. Janith ,&nbsp;H.S. Herath ,&nbsp;N. Hendeniya ,&nbsp;D. Attygalle ,&nbsp;D.A.S. Amarasinghe ,&nbsp;V. Logeeshan ,&nbsp;P.M.T.B. Wickramasinghe ,&nbsp;Y.S. Wijayasinghe","doi":"10.1016/j.jpbao.2023.100019","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100019","url":null,"abstract":"<div><p>Over the last two decades, surface plasmon resonance (SPR) sensors have advanced significantly, becoming an important tool in disciplines such as biosensing, chemical sensing, and material characterization. SPR has gained popularity in biosensing because of its great sensitivity and specificity in detecting biomolecular interactions. This review provides an overview of the recent developments of the SPR biosensor technology and its applications in medical diagnostics. To provide an up-to-date overview of the area, the review includes the most recent works from the last decade. Furthermore, it explores various configurations (prism, grating, fiber optic, waveguide modulated) and wave properties (angle, wavelength, phase) being tracked for sensing together with strategies for enhancing sensitivity and selectivity through mechanisms such as surface coatings, sensing mediums, and immobilization techniques.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"2 ","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49879898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluorescent nanoprobe prepared from hyaluronic acid modified iron selenide nanoparticles for real-time detection of hyaluronidase as tumor marker","authors":"Chaoqun Zhang ,&nbsp;Jie Song ,&nbsp;Xin Shen ,&nbsp;Qian Li ,&nbsp;Feng Su ,&nbsp;Suming Li","doi":"10.1016/j.jpbao.2023.100001","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100001","url":null,"abstract":"<div><p>A highly sensitive nanoprobe HAPPF@FeSe₂NPs was developed for real-time detection of hyaluronidase (HAase) as tumor marker. Hyaluronic acid (HA) was first functionalized with adipic acid dihydrazide (ADH) via amide formation. Carboxyl-terminated polylactide (PLA) was then grafted to HA-ADH using EDC/NHS as coupling agents, yielding an HA-ADH-PLA (HAP) graft copolymer. Iron selenide nanoparticles (FeSe₂NPs) were surface coated with HAP by ultrasonic assisted self-assembly. Finally, the resulted HAP@FeSe₂NPs were surface-modified with fluorescein isothiocyanate (FITC) and polyethyleneimine (PEI) to obtain HAPPF@FeSe₂NPs fluorescent nanoprobe. Analyses by FTIR, XRD, XPS, EDX, TEM, DLS, ¹H NMR and TGA confirmed the successful synthesis of the nanoprobe, and fluorescence spectroscopy proved its good detection performance. Moreover, cell imaging results demonstrated the ability of the nanoprobe to target tumor cells. MTT assay and hemolysis tests confirmed its good cyto- and hemo-compatibility. Therefore, it is concluded that HAPPF@FeSe₂NPs nanoprobe could be used in targeted tumor cell imaging for early diagnosis of cancers.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"1 ","pages":"Article 100001"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49883947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Label-free shotgun proteomics: Exploiting a reliable and sensitive method to monitor residual host-cell proteins in monoclonal antibody products","authors":"Somar Khalil,&nbsp;Adeline Wychowski,&nbsp;Cyrille Chéry,&nbsp;Annick Gervais","doi":"10.1016/j.jpbao.2023.100012","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100012","url":null,"abstract":"<div><p>The removal of host cell proteins (HCPs) remains a challenge in the downstream processing of monoclonal antibodies (mAbs). It is critical to monitor residual HCPs since they can have an impact on product stability and safety. The enzyme-linked immunosorbent assay (ELISA) only quantifies the total amount of HCPs and does not indicate the identity or quantity of any specific HCP. Mass spectrometry-based proteomics applications demonstrate an advantage in quantitatively profiling individual HCPs. However, technical reproducibility, dynamic range, and ensuring an acceptable statistical significance of scoring measurements are critical hurdles that ought to be overcome. In this paper, we describe a sensitive and reproducible shotgun proteomics approach that includes an efficient mAb depletion strategy and addresses the shortcomings of such workflows. Our methodology is potentially a valuable complement or alternative to ELISA. Additionally, it can facilitate the purification process development and the evaluation of ELISA kits upon process changes.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"1 ","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49883945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIP-based electrochemical sensor for highly selective and sensitive determination of entacapone from the triple mixture in tablet dosage form","authors":"Fatma Budak ,&nbsp;Ahmet Cetinkaya ,&nbsp;S. Irem Kaya ,&nbsp;Sibel A. Ozkan","doi":"10.1016/j.jpbao.2023.100005","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100005","url":null,"abstract":"<div><p>The aim of this study is to develop a molecularly imprinted polymer (MIP) sensor via photopolymerization for selective and sensitive analysis of entacapone (ENT), a catecholamine-o-methyl transferase (COMT) inhibitor. ENT is used for Parkinson’s disease treatment with levodopa (LEV) and carbidopa (CAR), and it is available in a triple combination tablet dosage form. For the MIP-based electrochemical sensor (4-AP@MIP/GCE) design, 4-aminophenol (4-AP) was selected as the functional monomer. Surface characterization of the 4-AP@MIP/GCE sensor was performed by scanning electron microscopy, electrochemical characterization by CV, and electrochemical impedance spectroscopy (EIS). The linear concentration range was between 1.0 pM and 10.0 pM under optimum conditions for ENT determination. The limit of detection (LOD) of 0.24 pM and the limit of quantification (LOQ) of 0.80 pM were calculated for ENT analysis using 4-AP@MIP/GCE. The accuracy was proven by performing a recovery study on the tablet sample that contains ENT, LEV, and CAR, and the recovery was found to be 99.32%. The selectivity of the 4-AP@MIP/GCE sensor for ENT has been proven by interference studies on LEV, CAR, and their binary mixtures. Looking at the results of the study, it has been proven that the 4-AP@MIP/GCE sensor is a highly selective, sensitive, and specific quantitative option for the analysis of ENT.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"1 ","pages":"Article 100005"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49883903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enantioseparation of new axially chiral carboxylic acids on polysaccharide-based chiral stationary phases under normal phase elution conditions","authors":"Barbara Sechi ,&nbsp;Victor Mamane ,&nbsp;Roberto Dallocchio ,&nbsp;Alessandro Dessì ,&nbsp;Sergio Cossu ,&nbsp;Giorgi Jibuti ,&nbsp;Paola Peluso","doi":"10.1016/j.jpbao.2023.100011","DOIUrl":"https://doi.org/10.1016/j.jpbao.2023.100011","url":null,"abstract":"<div><p>In the last decade, the availability of new and versatile synthetic strategies for the preparation of substituted 4,4’-bipyridyl derivatives based on chemo- and regioselective functionalization of the 4,4’-bipyridine core has encouraged studies for exploring the bioactivity of these compounds in the fields of drug discovery and medicinal chemistry. In substituted 4,4’-bipyridines, chirality may emerge from restricted rotation induced by sterically hindered atoms or functional groups located around the 4,4’-biaryl bond (chiral axis). The first atropisomeric substituted 4,4’-bipyridine was prepared in 2008, and no asymmetric synthesis to produce pure atropisomers of chiral 4,4’-bipyridine derivatives has been available so far. Thus, in the last few years, our groups developed methods to separate atropisomers of a wide series of 4,4’-derivatives by high-performance liquid chromatography (HPLC) using polysaccharide-based chiral stationary phases (CSPs). In the frame of our interest in this field, we reported herein the synthesis of two new chiral carboxylic acids containing an axially chiral 4,4’-bipyridyl unit as source of chirality, and their HPLC enantioseparation on polysaccharide-based CSPs. In particular, the impact of analyte and CSP structures on the enantioseparation outcomes as well as mechanisms and noncovalent interactions underlying the enantioseparation were explored by using electrostatic potential analysis and molecular dynamics (MD) simulations.</p></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"1 ","pages":"Article 100011"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49883946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}