Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Characterization of metabolites of ganoderic acids extract from Ganoderma lucidum in rats using UHPLC–MS/MS","authors":"Wenjing Liu ,&nbsp;Nian Wu ,&nbsp;Bo Peng ,&nbsp;Ting Li ,&nbsp;Luyao Ren ,&nbsp;Bo Li ,&nbsp;Yuelin Song","doi":"10.1016/j.jpba.2025.116764","DOIUrl":"10.1016/j.jpba.2025.116764","url":null,"abstract":"<div><div>Ganoderic acids, the primary active compound cluster in <em>Ganoderma lucidum</em> (Chinese name: <em>Lingzhi</em>), one of the most reputed herbal medicines, play a crucial role in its immunomodulatory, anti-inflammatory, and anticancer properties. To reveal the existence forms of this chemical cluster in rat, we characterized the herb-derived compounds following the oral administration of the ganoderic acids extract (GAE). Moreover, we conducted metabolite characterization for both ganoderic acid A (GAA) and ganoderic acid B (GAB) in parallel to explore the metabolic pathways for ganoderic acids. The biological samples, including bile, plasma, urine, and feces, were analyzed by UHPLC–MS/MS. After carefully summarizing the mass fragmentation rules of ganoderic acids, a total of thirteen and eleven were identified after oral administration of GAA and GAB, respectively, through converting MS/MS spectra into chemical structures. Oxidation, reduction, hydroxylation, glucuronidation and sulfation were proposed as the primary biotransformation routes, and thereof, hydroxylation accounted for more metabolite generation. Through applying mass fragmentation rules and the metabolic knowledge, 107 metabolites, in total, were identified as GAE-derived components in rat. The obtained results provided important information towards the therapeutical forms of GAE <em>in vivo</em>, and moreover, offered guidelines for metabolite characterization of, but not limited to, triterpenoids.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116764"},"PeriodicalIF":3.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479835","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 integrated analysis strategy for characterization of chromones and coumarins from Saposhnikovia divaricata (Turcz.) Schischk. by UHPLC-QTOF-MS","authors":"Zhi-Jiang Chen ,&nbsp;Wei Guan ,&nbsp;Yan-Ying Li ,&nbsp;Yu-Qing Wang ,&nbsp;Peng Jiang ,&nbsp;Yan Sun ,&nbsp;Zhi-Chao Hao ,&nbsp;Qing-Shan Chen ,&nbsp;Li-Li Zhang ,&nbsp;Shu Liu ,&nbsp;Hai-Xue Kuang ,&nbsp;Si-Tong Liu ,&nbsp;Yao-Xin Sui ,&nbsp;Bing-You Yang ,&nbsp;Yan Liu","doi":"10.1016/j.jpba.2025.116758","DOIUrl":"10.1016/j.jpba.2025.116758","url":null,"abstract":"<div><div>This study aimed to employ a comprehensive data screening strategy to identify the chromones and coumarins present in <em>Saposhnikovia divaricata</em> (SD). Initially, the five-point mass defect filter (MDF) method was utilized to screen the respective three subclasses of chromones and coumarins for MS¹. In comparison to the traditional MDF method, the number of interference peaks was reduced from 3462 to 1053, representing a decrease of 69.58 %. Then, diagnostic fragment ion filtering (DFIF) was used to screen product ions selected by MDF method, which was based on the fragmentation rules of each subclass to screen whether it met the conditions. Finally, we characterized 94 compounds from SD, including 40 chromones and 54 coumarins, among them, 82 chromones and coumarins were identified by combining the above two methods, 12 coumarins were identified by combining MDF and references, they were classified into other coumarins. Twenty one compounds were identified for the first time from SD, and 3 chromones and 7 coumarins were unknown compounds. Through untargeted metabolomics analysis of SD samples from 12 different regions, significant differences were found in SD samples from different areas, and 20 differential metabolites were distinguished, including 13 chromones and 7 coumarins. This study established for the first time a comprehensive strategy combining MDF, DFIF, and untargeted metabolomics to evaluate SD quality. The results indicated that this method is an efficient, accurate, and promising approach for classifying and exploring compounds in complex natural product systems, providing a basis for evaluating the quality of SD from different sources.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"259 ","pages":"Article 116758"},"PeriodicalIF":3.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465113","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 validation and pilot clinical application of a UPLC-MS/MS method for determining intracellular mycophenolic acid and metabolites in kidney transplant recipients","authors":"Xiaomei Chen ,&nbsp;Xinhua Dai ,&nbsp;Huan Xu ,&nbsp;Chunxia Chen ,&nbsp;Xueqaio Wang ,&nbsp;Yuangao Zou ,&nbsp;Hanjing Liu ,&nbsp;Yunying Shi ,&nbsp;Yi Li ,&nbsp;Yangjuan Bai","doi":"10.1016/j.jpba.2025.116748","DOIUrl":"10.1016/j.jpba.2025.116748","url":null,"abstract":"<div><div>There is no consensus on the strategy for therapeutic drug monitoring of the immunosuppressive drug mycophenolic acid (MPA) in organ transplant recipients. The present study proposes the utilization of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for determining the concentrations of MPA and its metabolites: 7-O-mycophenolic acid glucuronide (MPAG) and acyl mycophenolic acid glucoside (AcMPAG) in peripheral blood mononuclear cells (PBMCs). We aimed to assess the potential application of monitoring MPA and its metabolite concentrations in PBMCs in the infection after transplantation in Chinese kidney transplant recipients (KTRs). The UPLC-MS/MS method we developed demonstrated good linearity in the quantitative ranges of 0.05–50.00 ng/mL for MPA, 0.50–50.00 ng/mL for MPAG, and 0.10–20.00 ng/mL for AcMPAG. AcMPAG in PBMCs was unstable, degrading significantly after 48 h of storage at −80°C or after 3 freeze-thaw cycles. MPA and MPAG concentrations in KTRs' PBMCs exhibited high inter-individual variability, and the MPA concentration in PBMCs was poorly correlated with that in plasma (rs = 0.206, p = 0.117). Compared with the stable group, the infected group had significantly higher MPA concentration in PBMCs at 2 and 4 h post-dosing and in plasma at 4 h post-dosing (p &lt; 0.05). The receiver operating characteristic (ROC) analysis for post-transplantation infection revealed that PBMCs MPA-C4 and PBMCs-MPA-C2 possessed much better diagnostic efficiency than Plasma-MPA-C4. This method is easy-to-use and reliable, making it a promising clinical quantitative tool for MPA, MPAG, and AcMPAG in PBMCs. PBMC-MPA monitoring may be a potential biomarker for infection monitoring for KTRs.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"259 ","pages":"Article 116748"},"PeriodicalIF":3.1,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of stability-indicating UHPLC-UV-MS tandem methods for lenalidomide assay, related substances, and genotoxic impurity monitoring","authors":"Çağan Ağtaş ,&nbsp;Esen Bellur Atici","doi":"10.1016/j.jpba.2025.116757","DOIUrl":"10.1016/j.jpba.2025.116757","url":null,"abstract":"<div><div>Lenalidomide, a potent immunomodulatory drug, is widely used in the treatment of myelodysplastic syndrome. To investigate its degradation behavior under stress and stability testing conditions, we developed and validated a novel stability-indicating ultra-performance liquid chromatography (UHPLC)-UV-MS tandem method with high specificity, precision, accuracy, and robustness. An Acquity UPLC Phenyl column (100 × 2.1 mm, 1.7 µm) was used for impurity profiling and quantification of lenalidomide at a detection wavelength of 254 nm, with an injection volume of 1.0 µL and controlled sample and column temperatures of 15 °C and 30 °C, respectively. The diluent consisted of 0.1 % formic acid and acetonitrile (90:10, v/v), while the mobile phases were 0.1 % formic acid (Mobile Phase A) and acetonitrile (Mobile Phase B). A 20-minute gradient elution at a flow rate of 0.2 mL/min was used for impurity analysis, whereas a 7-minute gradient at 0.3 mL/min was applied for assay determination. The method demonstrated good linearity for all analytes, ensuring reliable quantification. Stress and photostability studies revealed that lenalidomide was stable under high temperatures (105 °C for 10 days) and daylight/UV exposure but exhibited significant degradation under hydrolytic and oxidative conditions. Hydrolysis led to the formation of major degradation products A, B, and E, whereas oxidative stress conditions generated impurities C (–NH₂ → –NO₂) and I (–NH₂ → –NH–OH). Methanol, commonly used in lenalidomide synthesis and analytical methods, was found to play a critical role in impurity formation. Methanolysis products J and K were identified as constitutional isomers arising from the ring-opening of the glutarimide moiety, which was confirmed by UHPLC-Q-TOF-MS and NMR analyses. The UHPLC-UV-MS method also reliably monitored the potentially genotoxic impurity G, classified as a Class 2 impurity according to ICH M7 guidelines, ensuring its levels remained below the Toxicological Threshold Concern (TTC, 1.5 µg/day, 60 ppm) for patient safety as per health authority requirements. This comprehensive analytical approach not only ensures the stability and safety of lenalidomide but also provides critical insights into its degradation pathways. The findings contribute to improved impurity control strategies, manufacturing process optimization, and regulatory compliance, benefiting the broader class of glutarimide-containing drug substances such as pomalidomide and thalidomide.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116757"},"PeriodicalIF":3.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445630","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 label-free electrochemical biosensor for rapid quantification of antimicrobial peptides in teleost fish mucus","authors":"Sonia Fekih-Zaghbib ,&nbsp;Sayda Dhaouadi ,&nbsp;Hiba Mejri ,&nbsp;Marwa Meftah ,&nbsp;Houyem Abderrazek ,&nbsp;Khaled Miled ,&nbsp;Zakaria Benlasfar ,&nbsp;Nadia Cherif ,&nbsp;Saloua Sadok ,&nbsp;Andrea Santulli ,&nbsp;Noureddine Raouafi ,&nbsp;Balkiss Bouhaouala-Zahar","doi":"10.1016/j.jpba.2025.116749","DOIUrl":"10.1016/j.jpba.2025.116749","url":null,"abstract":"<div><div>We used a thiol-faradaic electrochemical differential pulse voltammetry and impedance spectroscopy on a gold-modified screen-printed carbon electrode to quantify Chrysophsins antimicrobial peptides in the fish mucus without prior extraction. We have developed a specific anti-Chrysophsins polyclonal antibody and used ferrocene as a transducing system. The platform has a sensitivity of 30.5 nA.mL.ng⁻¹ (11.28 nA.nM⁻¹) in a linear range of 0.1–1 µg.mL⁻¹ and a limit of detection of 0.227 ng.mL⁻¹ (84.15 pM). Selectivity, accuracy, repeatability and stability were validated to meet the guidelines of ligand binding assays. Mean Chrysophsins levels in mucus pools from healthy and thermally unstressed <em>Argyrosomus regius</em>, <em>Dicentrarchus labrax</em> and <em>Sparus aurata</em> fish were 8.763 µM (± 0.007), 7.296 µM (± 0.023) and 8.296 (± 0.044) respectively, within the range of mass spectrometry gill values and below the minimum inhibitory concentration (MIC) of Chrysophsins for fish pathogens. The multi-infected <em>D. labrax</em> pool shows a significant decrease in concentration compared to the healthy and thermally stressed pools (p &lt; 0.0262) with 2.8 µM (± 0.024). The thermally stressed <em>A. regius</em> pool is not significantly different from the other pools with 8.763 µM (± 0.007). This electrochemical platform is a flexible tool for real-time targeting of peptide biomarkers in the real matrix and is suitable for mucosal fluids for early fish welfare monitoring.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116749"},"PeriodicalIF":3.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453905","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 revealed that quercetin improved spleen metabolism disorders and regulated the brain-spleen axis in perimenopausal depression model rats","authors":"Ranqi Yao,&nbsp;Wenqi Cui,&nbsp;Weidi Wang,&nbsp;Chenlu Feng,&nbsp;Ying Chen,&nbsp;Xiujuan Zhao","doi":"10.1016/j.jpba.2025.116744","DOIUrl":"10.1016/j.jpba.2025.116744","url":null,"abstract":"<div><div>Perimenopausal depression is a subtype of depression that seriously harms women's health. The pathogenesis of perimenopausal depression remains unclear, which limits its prevention and therapy. Quercetin is a flavonoid with antidepressant and estrogen-like effects. This study aimed to explore the effects of quercetin on spleen metabolism in rats with perimenopausal depression and its potential mechanism. Untargeted metabolomics was employed to obtain splenic metabolite profiles, and 21 differential metabolites were identified. Pathway analysis revealed that glycerophospholipid metabolism, retinol metabolism, steroid hormone biosynthesis, and linoleic acid metabolism were disturbed. Notably, Spearman’s rank correlation analysis revealed that differential metabolites were significantly correlated with behavioral test results (p &lt; 0.01). After treatment with quercetin, the intensities of the above differential metabolites were restored (p &lt; 0.01), indicating that quercetin can improve the spleen metabolic disorder induced by the perimenopausal depression model. Further study showed that quercetin can increase the expression of PPAR-α in the hippocampus and spleen, reduce the expression of NF-κB and the levels of TNF-α and IL-6 in the spleen, and restore the expression of CREB and BDNF in the hippocampus (p &lt; 0.05 or p &lt; 0.01). Our study is the first to explore the effect of quercetin on spleen metabolism disorders in perimenopausal depression model rats using untargeted metabolomics. Quercetin can improve spleen metabolism disorders through multiple pathways, which may be related to the restoration of hippocampal neuroplasticity and reduction of spleen inflammation by regulating the brain-spleen axis. Our study provides a potential strategy for preventing and treating perimenopausal depression.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116744"},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429704","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":"Validation of a quantitation method for conjugated quercetin in human plasma","authors":"Yui Sudaka ,&nbsp;Takafumi Mitsui ,&nbsp;Hiroaki Kida ,&nbsp;Mst. Julia Sultana ,&nbsp;Miyu Nishikawa ,&nbsp;Shinichi Ikushiro ,&nbsp;Naoto Yamaguchi","doi":"10.1016/j.jpba.2025.116738","DOIUrl":"10.1016/j.jpba.2025.116738","url":null,"abstract":"<div><div>Since the type of glycoside affects the pharmacokinetic profile of the aglycon after oral ingestion of quercetin glycosides, clinical studies on the pharmacokinetics of quercetin glycosides are required. However, a suitable method to determine the concentrations of quercetin phase II metabolites in human plasma and urine is lacking. Therefore, we developed and validated an LC-MS method for the quantitation of conjugated quercetin using relevant reference standards, including hetero-conjugates with glucuronic acid and sulfonic acid (QC-GA/S). Quercetin hetero-conjugates extracted from rat serum were used for the method development, and reference standards were biosynthesized for the quantitation. The use of a solid-phase extraction (SPE) column in a 96 well format enabled high-throughput analysis of up to 96 tests in a day, without compromising recovery and sensitivity. The SPE column with a weak anion exchange group contributed to the high recovery of QC-GA/S. The method was then validated, and its usefulness was confirmed using clinical samples. QC-GA/S was the predominant phase II quercetin metabolite after the ingestion of quercetin glucoside or quercetin supplements. Moreover, the two peaks of QC-GA/S found in human plasma and urine were isomers of QC-7GA/4’S, which has been reported as the predominant peak in rat plasma. If QC-GA/S in plasma is responsible for a physiological activity of quercetin, it is important to determine the concentration of each QC-GA/S isomer.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116738"},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420600","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":"Development and optimization of a high-throughput LC-MS/MS method for the simultaneous determination of Exatecan and its Cathepsin B-sensitive prodrug, and ARV-825 in rat plasma: Application to pharmacokinetic study","authors":"Xiaolan Xu,&nbsp;Yangyang Liu,&nbsp;Qing Yan,&nbsp;Chenxia Bai,&nbsp;Xiaohua Ran,&nbsp;Jing Li,&nbsp;Jiaming Zhang,&nbsp;Qikun Jiang,&nbsp;Tianhong Zhang","doi":"10.1016/j.jpba.2025.116746","DOIUrl":"10.1016/j.jpba.2025.116746","url":null,"abstract":"<div><div>For most cancers, the combination of chemotherapy drugs is a promising approach. The combination of DNA damage agent Exatecan and proteolysis targeting chimera (PROTAC) agent ARV-825, which is a selective bromodomain-containing protein 4 degrader, can further improve efficacy through the DNA damage-repair mechanism. The Cathepsin B-sensitive prodrug with high albumin affinity of Exatecan (C14-VC-PAB-Exa) was introduced and co-encapsulated with ARV-825 into the nano-drug delivery system for improving the physicochemical properties of the two drugs. To promote the translation of Exatecan and the PROTAC into the clinics, it is important to develop a reliable and high-throughput bioanalytical method for the simultaneous determination of Exatecan, C14-VC-PAB-Exa, and ARV-825 that can evaluate the pharmacokinetic behaviors of the analytes. In this study, an HPLC-MS/MS method after preparation by one-step protein precipitation was developed and fully validated. The analytes were eluted completely on a ZORBAX SB-C18 column by gradient elution. Multiple reaction monitoring mode with positive electrospray ionization was applied to quantify the analytes. The validated method on selectivity, linearity (<em>r</em> ≥ 0.995), precision and accuracy (&lt; 15 %), extraction recovery (&gt; 88.0 %), matrix effect (&lt; 9.1 %), carry-over, and stability were within the predefined acceptance criteria. The method was successfully applied to the pharmacokinetic study of Exatecan, C14-VC-PAB-Exa, and ARV-825 in rats for the first time. The proposed robust and economical method will be an alternative bioanalytical procedure for Exatecan and ARV-825 in the future. What is more, the present work could provide a reference for the clinical combination of the two drugs.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116746"},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420116","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":"Separation, characterization and cytotoxicity of unknown forced degradation impurity of selpercatinib using Prep-LC, HRMS and NMR","authors":"Qin Wang ,&nbsp;Wenyi Wu ,&nbsp;Rongwei Sun ,&nbsp;Liangliang Cai","doi":"10.1016/j.jpba.2025.116747","DOIUrl":"10.1016/j.jpba.2025.116747","url":null,"abstract":"<div><div>Selpercatinib (LOXO-292) is a newly marketed oral selective receptor tyrosine kinase inhibitor targeting rearranged during transfection (RET), demonstrating precise therapeutic effects against RET-positive non-small cell lung cancer and thyroid cancer. In this study, an unknown acid forced degradation impurity of selpercatinib, designated sel-1, was isolated and purified using semi-preparative liquid chromatography (semi-Prep-LC). The purified sel-1 showed a chromatographic purity of 99.1 % as determined by high-performance liquid chromatography (HPLC). It appeared as a white amorphous powder, with a maximum absorption peak at 235 nm and a chemical formula of C₂₈H₂₉N₇O₃. Its molecular structure was elucidated using high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR). sel-1 was identified as 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-oxo-1,6-dihydropyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-<em>a</em>]pyridine-3-carbonitrile. In vitro MTT assays revealed that sel-1 exhibited significant antitumor activity, particularly against HepaRG and MKN-1 cell lines, with stronger inhibition than selpercatinib. The study contributes to enhancing the quality control standards for selpercatinib and suggests that sel-1 holds potential for further drug development.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116747"},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of related substances in DTX-AI via LC–QTOF–HRMS","authors":"Peng-wei Hu ,&nbsp;Wen-yu Zou ,&nbsp;Zhao-guang Li ,&nbsp;Hai-dao Li ,&nbsp;Jun Liu ,&nbsp;Min Song ,&nbsp;Yu-ting Lu ,&nbsp;Tai-jun Hang","doi":"10.1016/j.jpba.2025.116739","DOIUrl":"10.1016/j.jpba.2025.116739","url":null,"abstract":"<div><div>10-<em>O</em>-4-Ketonephenyl carbamate docetaxel (DTX-AI) is a synthetic taxane compound that exerts antitumor effects by inhibiting microtubule depolymerization and promoting microtubule dimer synthesis. Owing to the poor water solubility of DTX-AI, the liposomal formulation for injection was developed and prepared. <em>In vitro</em> experiments showed that DTX-AI and its liposomal formulation outperformed DTX in terms of antitumor efficacy at much lower concentrations, with correspondingly lower toxicity. The quality and stability as well as liposomal formulation of DTX-AI directly impact its therapeutic efficacy and safety. This study utilized LC–QTOF–HRMS to isolate and identify the process and stress testing degradation related substances (RSs) in DTX-AI. A total of 23 RSs were detected and identified in the Active pharmaceutical ingredient (API) via positive ESI–HRMS, and their structures and degradation pathways were elucidated and summarized. These findings provide valuable insights into the optimal production processes, formulations, storage conditions, and quality control for DTX-AI.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"258 ","pages":"Article 116739"},"PeriodicalIF":3.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420115","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}