Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Metabolomic analysis reveals the potential of fucosylated chondroitin sulfate from sea cucumber in modulating metabolic homeostasis","authors":"Piaopiao Qiu ,&nbsp;Aihua Xia ,&nbsp;Xinying Yang ,&nbsp;Lin Yi ,&nbsp;Yilan Ouyang ,&nbsp;Yiming Yao ,&nbsp;Haiying Liu ,&nbsp;Liang Li ,&nbsp;Zhenqing Zhang","doi":"10.1016/j.jpba.2024.116509","DOIUrl":"10.1016/j.jpba.2024.116509","url":null,"abstract":"<div><div>In this study, we prepared four derivatives of fucosylated chondroitin sulfate (FCS): full-length FCS (flFCS) from <em>Holothuria leucospilota</em>, low molecular weight FCS (lmFCS) derived from flFCS, and their de-branched counterparts, de-branched flFCS (d-flFCS) and de-branched lmFCS (d-lmFCS) via controlled acid treatment. Following structural verification using various analytical techniques, we applied targeted metabolomics to examine the impact of FCS on nutritional efficacy and its structure-activity relationship. Analysis of 225 plasma and feces samples from 75 mice revealed a positive correlation between metabolomic shifts and increased weight gain, underscoring FCS’s potential to enhance nutrient absorption and promote growth. The observed linear relationship between the levels of short-chain fatty acids in plasma and feces suggests that FCS may facilitate catabolic activities in the gastrointestinal tract. The comparative study of different FCS derivatives on mouse growth and metabolic homeostasis regulation led to the conclusion that FCS exhibits greater biological activity with a higher degree of branching and larger molecular weight.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116509"},"PeriodicalIF":3.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446663","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":"Metagenomics combined with untargeted metabolomics to study the mechanism of miRNA-150-5p on SiO2 -induced acute lung injury","authors":"Xiaodong Wu ,&nbsp;Ling Qin ,&nbsp;Miao Song ,&nbsp;Chuanming Zhang ,&nbsp;Jingjing Guo ,&nbsp;Zheng Yang ,&nbsp;Zhixiang Gao ,&nbsp;Min Qiu","doi":"10.1016/j.jpba.2024.116515","DOIUrl":"10.1016/j.jpba.2024.116515","url":null,"abstract":"<div><div>Acute lung injury is a significant global health issue, and its treatment is becoming a hot topic of the researchers. To investigate the feasibility of miRNA-150–5p tail vein injection in the treatment of SiO₂-induced acute lung injury through the regulation of gut microbiota and serum metabolites based on multiomics technology. Twenty-four mice were randomly divided into the control, SiO₂ and miRNA-150–5p intervention groups. The SiO₂ and miRNA-150–5p intervention groups received a single intranasal dose of 100 µL 4 % SiO₂ suspension. Meanwhile, the miRNA-150–5p intervention group was administered with two tail vein injections of miRNA-150–5p (15 nmol each per mouse) on the day of successful modelling and on the third day post modelling. Metagenomics and metabolomics techniques were used to measure gut microbiota and serum metabolites, respectively. Tail vein injection of miRNA-150–5p improved SiO₂-induced acute lung injury and reduced the secretion of inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1β. These conditions altered the structure of gut microbiota, which resulted in the notable modulation of eight species at the species level. In addition, tail vein injection of miRNA-150–5p considerably reduced the levels of substances, such as phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol, in the glycerophospholipid metabolism and glycosylphosphatidylinositol–anchor biosynthesis pathways. Tail vein injection of miRNA-150–5p can alleviate acute lung injury. Combined metagenomics and untargeted metabolomics revealed the miRNA-150–5p-mitigated SiO₂-induced acute lung injury that occurred through the regulation of gut microbiota and serum metabolites.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116515"},"PeriodicalIF":3.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441583","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":"Inter-laboratory study for extraction testing of medical devices","authors":"David M. Saylor,&nbsp;Robert M. Elder,&nbsp;Kaleb Duelge,&nbsp;Nimesh P.R. Ranasinghe Arachchige,&nbsp;David D. Simon,&nbsp;Samanthi Wickramasekara,&nbsp;Joshua A. Young","doi":"10.1016/j.jpba.2024.116496","DOIUrl":"10.1016/j.jpba.2024.116496","url":null,"abstract":"<div><div>Biocompatibility evaluation of medical devices often relies on chemical testing according to ISO 10993–18 as a critical component for consideration. However, the precision associated with these non–targeted chemical characterization assessments has not been well established. Therefore, we have conducted a study to characterize intra–laboratory (repeatability) and inter–laboratory (reproducibility) variability associated with chemical testing of extractables from polymeric materials. To accomplish this, this study focused on two polymers, each with nine chemicals that were intentionally compounded into the materials. Eight different laboratories performed extraction testing in two solvents and subsequently characterized the extracts using gas chromatography and liquid chromatography methods. Analysis of the resulting data revealed the central 90 % range for the repeatability and reproducibility relative standard deviations are (0.09, 0.22) and (0.30, 0.85), respectively, for the participating laboratory methods. This finding implies that if the same sample was tested by two different laboratories using the same extraction conditions, there is 95 % confidence for 95 % of systems that the test results could exhibit differences up to 240 %. While the study was not designed to evaluate the relative impact of specific underlying factors that may contribute to variability in quantitation, the data obtained suggest the variability associated with analytical method alone is a substantial contribution to the overall variability. The relatively large reproducibility limits we observed may have significant implications where variability in extraction measurements can impact aspects of biocompatibility risk evaluation, such as exposure dose estimation and chemical equivalence assessments.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116496"},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432583","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":"Metabolomics analysis of Cucumis melo var. flexuosus organs in correlation to its anti-inflammatory activity aided by chemometrics","authors":"Hesham M. El-Sayed ,&nbsp;Dalia M. Rasheed ,&nbsp;Engy A. Mahrous ,&nbsp;Basma M. Eltanany ,&nbsp;Zeinab M. Goda ,&nbsp;Laura Pont ,&nbsp;Fernando Benavente ,&nbsp;Essam Abdel-Sattar","doi":"10.1016/j.jpba.2024.116512","DOIUrl":"10.1016/j.jpba.2024.116512","url":null,"abstract":"<div><div>Snake melon (<em>Cucumis melo</em> var. <em>flexuosus</em>, CM) is a gourd with health-promoting nutritional traits and unexplored phytochemicals. This study aims to comprehensively investigate the phytoconstituents in the fruits, leaves, roots, seeds, and stems of CM, using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Consequently, 118 metabolites were identified, encompassing phenolic compounds, flavonoids, megastigmanes, lignans, cucurbitacins, and fatty acids. Multivariate data analysis revealed differences in the metabolite composition of CM organs and correlated these variations with the potential <em>in-vitro</em> anti-inflammatory properties assessed against RAW 264.7 macrophages through the down-regulation of cyclo-oxygenase-Ⅱ, nuclear factor-kappa B, and tumor necrosis factor-<em>α</em>. The results indicated that leaf and seed extracts showed the highest anti-inflammatory activity due to their enrichment in several flavonoids, phenolic glycosides, and a megastigmane. These findings emphasize the health benefits of CM organs as potential functional foods and functional food by-products, serving as a natural source for developing new anti-inflammatory agents.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116512"},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423402","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":"Simultaneous detection of myostatin-targeting monoclonal antibodies in dried blood spots and plasma using liquid chromatography-tandem mass spectrometry with field asymmetric ion mobility spectrometry","authors":"Hyeon-Jeong Lee ,&nbsp;Jiin Hwang ,&nbsp;Yoondam Seo ,&nbsp;Gahyeon Lee ,&nbsp;Hwa Jeong Lee ,&nbsp;Hophil Min","doi":"10.1016/j.jpba.2024.116518","DOIUrl":"10.1016/j.jpba.2024.116518","url":null,"abstract":"<div><div>Transforming growth factor-β superfamily members, such as myostatin, growth/differentiation factor 11, and activin A, negatively regulate skeletal muscle mass. Inhibitors targeting these cytokines or activin receptor type IIB have the potential to treat muscular diseases and enhance physical performance. However, because of their effects on muscle mass and potential misuse, they are strictly prohibited in sports. Given the high potential for misuse as a doping agent in sports, effective analytical methods for these prohibited antibodies targeting these specific cytokines or their receptor are critically needed. In this study, we aimed to develop and validate a multitarget method to detect the prohibited transforming growth factor-β superfamily-targeting monoclonal antibodies, such as landogrozumab, domagrozumab, and the activin receptor type IIB-targeting antibody, bimagrumab, in human plasma and dried blood spot (DBS) samples using liquid chromatography-tandem mass spectrometry. Antibodies were purified from both the DBS and plasma samples using protein G magnetic beads and field-asymmetric ion mobility spectrometry (FAIMS) to minimize interference, followed by liquid chromatography-tandem mass spectrometry analysis. The validation process included tests for specificity, selectivity, linearity, limit of detection (LOD), limit of identification, precision, recovery, carryover effect, and matrix effect. The LODs for the target antibodies were identical in both DBS and plasma samples at 0.1 µg/mL for landogrozumab heavy and light chains, as well as 0.25 µg/mL for the domagrozumab light chain and 0.25 µg/mL for the bimagrumab heavy chain. However, the heavy chain of domagrozumab exhibited an LOD of 0.5 µg/mL in DBS and 1 µg/mL in plasma. The analytical method demonstrated strong linearity, with R² values greater than 0.99 for both plasma and DBS, and no carryover effect. Precision (CV%) was below 15 % at both middle (1 or 5 µg/mL; specific to the heavy chain of domagrozumab in plasma) and high (10 µg/mL) concentrations and was less than 20 % at the LOD. The selectivity and specificity indicated no interference in the analysis of target mAbs in different blood samples. Recovery was 31.6–49.8 % for DBS and 51.4–85.3 % for plasma, with no significant matrix effect. This study provides an effective method for doping analysis and novel protein detection.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116518"},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423389","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":"To explore the mechanism of gypenosides in the treatment of liver injury in rats based on GC-MS metabolomics and bile acid metabolism pathway","authors":"Zhiru Zhang ,&nbsp;Rong Yue ,&nbsp;Yibo Wang ,&nbsp;Lizhou Ma ,&nbsp;Miao Wang ,&nbsp;Yu Chen","doi":"10.1016/j.jpba.2024.116506","DOIUrl":"10.1016/j.jpba.2024.116506","url":null,"abstract":"<div><div>Gynostemma pentaphyllum is a herbaceous vine of Cucurbitaceae family, and its principal pharmacological components, gypenosides (GPs), have been proved to be effective in various liver diseases. However, the mechanisms of GPs on liver injury are still to be studied for further. This investigation utilized the CCl₄-induced liver injury rat model (LI) to comprehensively explore the mechanism of action of GPs in the treatment of chemical liver injury by comparing the metabolomic changes in four groups rats. In this study, the therapeutic efficacy of GPs in a liver injury rat model induced by weekly gavage of CCl₄ was evaluated by inflammatory factors, oxidative damage indexes, and histopathological sections. Then, GC-MS technology was used to identify the metabolic profile of GPs in treating liver injury. Finally, the content variation of metabolites (BAs and SCFAs) was measured to elucidate the mechanism of GPs in the treatment of CCl₄-induced liver injury. After 8 weeks of administration, GPs effectively reduced the degree of LI and appeared a substantial tendency of reversing in the levels of MDA, GSH, CYP7E1, CYP7A1 and CYP27A1. Untargeted metabolomics suggested that GPs may play a role in BAs and SCFAs metabolism. Targeted metabolomics and ELISA confirmed the key role of GPs in increasing SCFAs levels and regulating BAs metabolism. Overall, this study indicated that GPs can alleviate CCl₄-induced liver injury. And GPs may exert beneficial effects on LI by affecting their metabolites (SCFAs and BAs).</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116506"},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441585","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":"Integrated network pharmacology, metabolomics and molecular docking analysis to reveal the mechanisms of quercetin in the treatment of hyperlipidemia","authors":"Tao Chen ,&nbsp;Tongtong Wang ,&nbsp;Yuanxiang Shi ,&nbsp;Jun Deng ,&nbsp;Xiao Yan ,&nbsp;Chenbin Zhang ,&nbsp;Xin Yin ,&nbsp;Wen Liu","doi":"10.1016/j.jpba.2024.116507","DOIUrl":"10.1016/j.jpba.2024.116507","url":null,"abstract":"<div><div>Hyperlipidemia (HLP) is a significant contributor to cardiovascular diseases. Quercetin (QUE), a naturally occurring flavonoid with diverse bioactivities, has garnered attention due to its potential therapeutic effects. However, the precise mechanisms underlying the effects of QUE on HLP remain unclear. In this study, an ultra-high-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive-MS) metabolomics strategy was employed to obtain metabolite profiles, and potential biomarkers were identified following data analysis. Network pharmacology and Drug Affinity Responsive Target Stability (DARTS) assays were utilized to explore the potential targets of QUE for HLP treatment. The results of metabolomics and network pharmacology were then integrated to identify the key targets and metabolic pathways involved in the therapeutic action of the QUE against HLP. Molecular docking and experimental validation were performed to confirm these key targets. A comprehensive database search identified 138 QUE-HLP-related targets. A protein-protein interaction (PPI) network was constructed using STRING, and the shared targets were filtered with Cytoscape. Among these, AKT1, TNF, VEGFA, mTOR, SREBP1, and SCD emerged as potential therapeutic targets. These findings were validated using in vitro cell experiments. Additionally, the mechanism of action of QUE against HLP was evaluated by integrating network pharmacology with metabolomics, identifying two metabolomic pathways crucial to HLP treatment. DARTS experiments confirmed the stable binding of QUE to FASN, p-mTOR, SREBP1, and p-AKT. In HepG2 cells treated with palmitic acid (PA), QUE significantly reduced the mRNA expression of ACLY, ACACA, FASN, and SCD (<em>p</em> &lt; 0.05). Western blot analysis revealed that PA significantly increased protein expression of p-mTOR, SREBP1, FASN, and p-AKT (<em>p</em> &lt; 0.05). In summary, our study provides novel insights into the protective mechanisms of QUE against HLP and offers valuable information regarding its potential benefits in clinical treatment.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116507"},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391319","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":"Comparative profiling of the absorbed compounds and metabolites, and pharmacokinetic studies of Danshen-Chuanxiong herb pair in rat plasma and brain using liquid chromatography-tandem mass spectrometry","authors":"Jia-Xiu Guo ,&nbsp;Yang Yang ,&nbsp;Yong-Juan Zhao ,&nbsp;Jian Wang ,&nbsp;Hui Liu ,&nbsp;Li Xu ,&nbsp;Bing-Chun Yan ,&nbsp;Han-Qing Pang","doi":"10.1016/j.jpba.2024.116519","DOIUrl":"10.1016/j.jpba.2024.116519","url":null,"abstract":"<div><div>Danshen-Chuanxiong (DS-CX) was a classic herb pair commonly used to treat ischemic stroke. Nevertheless, the metabolic conversion and pharmacokinetic behavior of DS-CX <em>in vivo</em> remains unclear. This work aimed to reveal the <em>in vivo</em> metabolic behavior of DS-CX through establishing metabolic profiles and performing multicomponent pharmacokinetics analysis. The mass defect filtering (MDF) strategy integrated with UHPLC-QTOF-MS was firstly developed to characterize the metabolites of DS-CX in rats’ plasma and brain. Moreover, a sensitive UHPLC-QQQ-MS method was utilized to perform the comparative pharmacokinetic studies of major active ingredients of DS-CX in rats’ plasma. A total of 111 exogenous compounds (29 prototype compounds and 82 metabolites) were identified in rat biological samples. The major metabolic pathways were hydroxylation, methylation, deoxidation, dehydration, hydrogenation, demethylation, hydrolysis, decarboxylation and glucuronidation binding reactions. According to the results of metabolites profiling, sixteen active compounds (8 phenolic acids, 5 phthalides and 3 tanshinones) were selected as markers for further comparative pharmacokinetics study. Compared with the oral administration of DS or CX alone, the higher C_max of salvianolic acid B, crytotanshinone and tanshinone IIA; the shorter T_max of lithospermic acid, rosmarinic acid and tanshinone IIA; as well as the higher AUC_0−∞ of ferulic acid, rosmarinic acid, salvianolic acid B, senkyunolide I and crytotanshinone, could be found after co-administration of DS-CX (<em>P</em> &lt; 0.05). This study provided the overall knowledge of metabolites profiling of DS-CX <em>in vivo</em>, which would help to understand the effective material basis and promote the clinical application of DC-CX herb pair.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116519"},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423349","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 two‑sample Mendelian randomization study of lipidome and lung cancer","authors":"Zhang Fan","doi":"10.1016/j.jpba.2024.116514","DOIUrl":"10.1016/j.jpba.2024.116514","url":null,"abstract":"<div><div>We analyzed the potential relationship between liposomes and lung cancer risk for the first time using MR analysis methods. The results showed that sterol ester, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, and triacylglycerol may affect lung cancer risk. However, molecules with different fatty acid compositions also affect lung cancer risk differently. These results may help researchers discover more mechanisms by which lipid metabolism disorders support lung cancer growth and potential targets of lipid metabolism, giving more theoretical support to lung cancer therapeutic approaches that target lipid metabolic pathways.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116514"},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423350","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 application of hydrophilic interaction liquid chromatography for the identification of compounds with intramolecular hydrogen bonds","authors":"Alessandra Pugliano,&nbsp;Bernd Kuhn,&nbsp;Nenad Manevski,&nbsp;Björn Wagner,&nbsp;Matthias Beat Wittwer","doi":"10.1016/j.jpba.2024.116499","DOIUrl":"10.1016/j.jpba.2024.116499","url":null,"abstract":"<div><div>The incorporation of intramolecular hydrogen bonds (IMHB) into small molecules constitutes an interesting optimization strategy to afford potential drug candidates with enhanced solubility as well as permeability and consequently improved bioavailability (if metabolic stability is high). Common methods to assess IMHB rely on spectroscopic or diffraction techniques, which, however, have limited throughput when screening for hit compounds in early phases of drug discovery. Inspired by literature findings using supercritical fluid chromatography (SFC) as an indirect method for IMHB identification in a screening context, we aimed at developing a secondary chromatographic methodology taking advantage of commonly used HPLC-MS instrumentation. In this work, we explored hydrophilic interaction liquid chromatography (HILIC) and developed a method for discriminating compounds based on their hydrogen bonding features. By quantifying retention of different matched molecular pairs (MMP) and using information about their low energy conformations from quantum-mechanical calculations, we defined a hydrogen bonding-driven adsorption (k_ads) chromatographic parameter to assess a compound’s propensity to forming IMHB. In addition to the MMP analysis, we found that the k_ads parameter allows for the differentiation of analytes forming IMHB regardless of the comparison with control compounds.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116499"},"PeriodicalIF":3.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441584","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}