Journal of Chromatography B最新文献

{"title":"Integration of UHPLC-MS and mass spectrometry imaging techniques revealed the protective mechanism of Gushudan in postmenopausal osteoporosis rats via branched-chain amino acid metabolism based on the ‘kidney-bone’ axis","authors":"Mengxin Ren,&nbsp;Yajing Wang,&nbsp;Yue Yuan,&nbsp;Hailing Du,&nbsp;Qinghua Liang,&nbsp;Feng Qin,&nbsp;Zhili Xiong","doi":"10.1016/j.jchromb.2025.124540","DOIUrl":"10.1016/j.jchromb.2025.124540","url":null,"abstract":"<div><div>According to the theory of traditional Chinese medicine, the kidney is regarded as governing the bones and dominating the storage of essence. Gushudan (GSD) is a traditional Chinese medicine prescription that has the effects of strengthening bone and nourishing the kidney. However, the mechanism of action of GSD in preventing postmenopausal osteoporosis (PMOP) rats based on the ‘kidney-bone’ axis remains to be further systematically investigated. In this study, an integrated kidney metabolomics method based on three MS detection modes of UHPLC-HRMS, UHPLC-MS/MS and AFADESI-MSI was developed to reveal the protective mechanism of GSD in PMOP rats. Firstly, the non-targeted metabolomics was investigated to comprehensively explore the metabolic changes in the kidneys of PMOP rats based on the UHPLC-Q-Orbitrap HRMS. Subsequently, UHPLC-MS/MS targeted metabolomics and Mass Spectrometry Imaging (MSI) techniques were combined to elucidate the preventive mechanism of GSD on PMOP through branched-chain amino acid (BCAA) metabolism. The results of the non-targeted metabolomics demonstrated that GSD significantly modulated the levels of 67 potential biomarkers, including leucine and valine, which are primarily involved in amino acid metabolism. Specifically, BCAA metabolism is notably enriched in amino acid metabolism. Compared to the control group, it was found that the levels of BCAAs were decreased and α-branched-chain keto acids (BCKAs) were increased in the model groups in the targeted metabolomics study. Moreover, MSI results showed that the changes in BCAAs content were mainly concentrated in the renal cortex. This finding confirmed the metabolic disorders of BCAA in the renal cortex of PMOP rats, and that GSD had a significant regulatory effect on this disorder. In conclusion, this study integrated three mass spectrometry techniques that validate and complement each other to revealed the anti-osteoporostic mechanism of GSD in PMOP rats and to elucidate the modern scientific connotation of the ‘kidney-bone’ axis based on the BCAA metabolism.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1256 ","pages":"Article 124540"},"PeriodicalIF":2.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512226","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":"Pharmacokinetics comparison of seven active components after oral administration of Zhizhu pill using raw and processed Rhizoma Atractylodis Macrocephalae","authors":"Liu Si-qi ,&nbsp;Zheng Wei ,&nbsp;Zang Bin-ru ,&nbsp;Wu Hao ,&nbsp;Zhang Ke ,&nbsp;Liu Xiang ,&nbsp;Yuan Chu ,&nbsp;Zhao Qi-miao ,&nbsp;Shan Guo-shun","doi":"10.1016/j.jchromb.2025.124521","DOIUrl":"10.1016/j.jchromb.2025.124521","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Zhizhu pills (ZZP) is a Traditional Chinese Medicine that has been extensively applied in the treatment of spleen deficiency and constipation for many years. As a commonly used prescription in Traditional Chinese medicine, there had been a controversy over whether to use raw Rhizoma Atractylodis Macrocephalae (RRAM) or Bran-Fired Rhizoma Atractylodis Macrocephalae (BRAM) in ZZP. In this study, a specific, sensitive, fast and accurate liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to analyze the main active components in ZZP. It was used to determine the compound of Atractylenolide I, Atractylenolide III, Synephrine, Nuciferine, Narirutin, Naringin and Hesperidin in rat various biological matrices (plasma, tissue, urine and feces). The liquiritin was used as the internal standard. All the biological samples were prepared using a simple protein precipitation with acetonitrile and methanol (1:1, &lt;em&gt;V&lt;/em&gt;/V). A waters UPLC HSS T3 (100 × 2.1 mm, 1.8 μm) column was used in this research. The mobile phase consisting of 0.1 % aqueous formic acid (A)-0.1 % formic acid in acetonitrile (B) was employed to separate seven components from endogenous interferences. The components were detected with a triple quadrupole mass spectrometer using positive and negative ion multiple reaction monitoring (MRM) mode. The newly developed method was successfully applied to investigate the pharmacokinetics, tissue distribution and excretion of seven components after intragastric administration ZZP which was composed with RRAM or BRAM in rats. The pharmacokinetic results indicated that seven active components can be quickly absorbed and had undergone the enterohepatic circulation. It could also indicate higher &lt;em&gt;C&lt;/em&gt;&lt;sub&gt;max&lt;/sub&gt; of Nuciferine, Narirutin, Naringin and Hesperidin in the plasma after intragastric administration ZZP compose of BRAM than RRAM. In tissue distribution, the seven active components in ZZP were mainly distributed in the stomach, large intestine and small intestine. It could indicate a lower &lt;em&gt;C&lt;/em&gt;&lt;sub&gt;max&lt;/sub&gt; of Atractylenolide I, Atractylenolide III in the stomach, large intestine and small intestine after intragastric administration ZZP compose of BRAM compared to RRAM. It could also indicate higher Cmax of Narirutin, Naringin, and Synephrine in the stomach, large intestine and small intestine after intragastric administration ZZP compose of BRAM than RRAM. The results of the excretion study showed that the total urinary excretion rate of the 7 active components at 48 h was lower after intragastric administration ZZP compose of BRAM than RRAM. Meanwhile, the total fecal excretion rate of the 7 active components was higher after intragastric administration ZZP compose of BRAM than RRAM. The pharmacokinetics, tissue distribution and excretion characteristics of seven active components in ZZP were first revealed. It also used to compare the difference of ZZP compose of BRAM than RRAM in the pha","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1256 ","pages":"Article 124521"},"PeriodicalIF":2.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487926","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":"Serum untargeted metabolomics combined with mouse models reveals potential mechanisms of ChengShu QingChu decoction for the treatment of vitiligo","authors":"Xiangran Liu ,&nbsp;Abudureyimu Alimujiang ,&nbsp;Wenjing Wei ,&nbsp;Dengqiu Xu ,&nbsp;Tuerxun Wufuer ,&nbsp;Julaiti Abuduwayiti ,&nbsp;Shixia Huo ,&nbsp;Zhijian Li","doi":"10.1016/j.jchromb.2025.124538","DOIUrl":"10.1016/j.jchromb.2025.124538","url":null,"abstract":"<div><div>To illustrate the potential immunological mechanisms of ChengShu QingChu Decoction (CSQC) in vitiligo treatment. An untargeted metabolomic approach was used to detect serum metabolites in 30 patients with progressive vitiligo. Annotation of the differential metabolites were performed using MetaboAnalyst 5.0 and the KEGG database. In addition, 58 Hub genes associated with metabolic pathways were obtained from the GSEA and KEGG databases, and functional enrichment for Hub genes. Finally, it was validated by a mouse model. 102 down-regulated and 86 up-regulated metabolites were detected in serum. The main metabolic pathways enriched for differential metabolites were sphingolipid metabolism and glycerophospholipid metabolism, and the signaling pathways included PI3K-Akt and JAK-STAT signaling pathways, and immune cells included CD56 bright natural killer cell and Central memry CD8 T cell. In the mouse model, a significant decrease in the number of CD8⁺T cells as well as a decrease in the mRNA expression of JAK1, JAK2, and STAT1 was observed in addition to a trend toward increased melanocytes after drug treatment. This study utilizes metabolomics and bioinformatics analyses, combined with in vivo experimental validation, to elucidate the potential mechanism of CSQC in the treatment of vitiligo.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1256 ","pages":"Article 124538"},"PeriodicalIF":2.8,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549706","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":"Finger-prick blood sampling using volumetric absorptive microsampling (VAMS) method for monitoring the main (poly)phenolic metabolites in human blood after barley biscuit intake","authors":"María-Engracia Cortijo-Alfonso ,&nbsp;Silvia Yuste ,&nbsp;Carme Piñol-Felis ,&nbsp;María-Paz Romero ,&nbsp;Alba Macià ,&nbsp;Laura Rubió-Piqué","doi":"10.1016/j.jchromb.2025.124527","DOIUrl":"10.1016/j.jchromb.2025.124527","url":null,"abstract":"<div><div>A novel method based on volumetric absorptive micro-sampling (VAMS) combined with UPLC-MS/MS was developed and validated to determine the principal (poly)phenolic metabolites in human blood following the consumption of 140 g of purple whole-grain barley (WGB) biscuits. Finger-prick blood samples were collected from 11 healthy volunteers at multiple time points up to 48 h post-ingestion. To extract (poly)phenolic metabolites efficiently, various extraction parameters were optimized. Then, the method was successfully applied and five colonic (poly)phenolic metabolites from the main (poly)phenolic families from barley were detected: benzene-1,2-diol-<em>O</em>-sulphate, 3-(4′-hydroxy-3′-methoxy)propanoic acid and its sulphated form, 5′-(3′,4′-dihydroxyphenyl)-γ-valerolactone-<em>O</em>-sulphate, and methyl luteolin-<em>O</em>-glucuronide. Maximum absorption occurred at 12 h for most metabolites, while luteolin-<em>O</em>-glucuronide showed two distinct peaks at 2 and 6 h, indicating its dual-phase absorption. Comparison with venous plasma samples collected during the 0–6 h period showed no significant differences (<em>p</em> &gt; 0.05), validating the statistical reliability of VAMS as an alternative to venipuncture. Thus, VAMS emerges as a less invasive and statistically robust means for analyzing the pharmacokinetic profile of (poly)phenols, particularly those arising from colonic metabolism.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1256 ","pages":"Article 124527"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487927","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 analysis of 203 drugs of abuse and metabolites in urine samples using liquid chromatography–tandem mass spectrometry","authors":"Sangeun Lee ,&nbsp;Jihyun Lee ,&nbsp;Dain Jang ,&nbsp;Hee-jung Cho ,&nbsp;Seonmi Choi ,&nbsp;Eunbin Ryu ,&nbsp;Wonhee Koo ,&nbsp;Jaewoo Song ,&nbsp;Jea-sung Pyo ,&nbsp;Na Young Lim ,&nbsp;Chan Hyeok Kwon ,&nbsp;Kikyung Jung ,&nbsp;Jin Young Kim ,&nbsp;Sungill Suh ,&nbsp;Youngmin Hong ,&nbsp;Eunyoung Han","doi":"10.1016/j.jchromb.2025.124524","DOIUrl":"10.1016/j.jchromb.2025.124524","url":null,"abstract":"<div><div>The issue of drug abuse is increasingly becoming a significant concern worldwide. However, the simultaneous detection of a wide spectrum of drug of abuse (DOA), especially in biofluids, is challenging due to their diverse and varied physicochemical properties and matrix effects. Herein, we have developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous detection of 203 DOAs, including amphetamines, opiates, cathinones, phencyclidines, synthetic cannabinoids, cocaine, and metabolites, in 100 μL of urine. A mass analysis was performed using multiple reaction monitoring mode with an electrospray ionization source. The run time of the developed method was 16 min. Two sample preparation methods were compared for urine samples: enzymatic hydrolysis followed by either dilution or QuEChERS. Both methods demonstrated good linearity and low matrix effects; however, the dilution method showed superior accuracy and precision. Method validation was conducted to assess the efficacy of the developed method. The LC-MS/MS method with the dilution method demonstrated good linearity with the coefficients of determination (R²) above 0.99 for 200 compounds. The limit of quantification (LOQ) ranged from 0.1 to 20.0 ng/mL. The inter-day precision was below 20 % for all 203 compounds, with a bias of ±20 % for 198 compounds. This method was successfully applied to 40 real urine samples. The developed method allows the simultaneous separation and detection of a variety of DOAs with diverse physicochemical properties in a small amount of urine. Furthermore, the technique could be adapted to fit the practical requirements of forensic investigations, thereby enhancing its effectiveness and reliability.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1256 ","pages":"Article 124524"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549624","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":"Improved analysis HPLC-ESI/triple method for mapping the methotrexate by mass spectrometry","authors":"Haihong Jia ,&nbsp;Ruihong Li ,&nbsp;Yahui Li ,&nbsp;Fen Lu ,&nbsp;Lan Ma ,&nbsp;Xiujuan Xu","doi":"10.1016/j.jchromb.2025.124529","DOIUrl":"10.1016/j.jchromb.2025.124529","url":null,"abstract":"<div><div>Methotrexate is a commonly utilized agent in pediatric oncology therapy. However, significant interindividual variability in its clearance can lead to delayed clearance and resultant severe toxicity. This underscores the urgent need for efficient and sensitive analytical methods to ensure patient safety. In this study, we aimed to establish a high-performance liquid chromatography-tandem mass spectrometry (HPLC-ESI/triple) method for the quantitative determination of methotrexate concentrations in plasma. This method is intended to facilitate therapeutic drug monitoring in pediatric patients, thereby allowing for a better understanding of the pharmacokinetics of methotrexate in vivo. The results indicate that the established HPLC-ESI/triple method can accurately and sensitively quantify methotrexate using only 10 μL of plasma. The recovery rates for all analytes exceeded 90 %, and matrix effects were minimal. Furthermore, our optimized method revealed that patient age significantly influences methotrexate blood concentration. Specifically, under identical dosage and administration intervals, an increase in patient age correlates with a decrease in measured blood concentration. Additionally, our findings suggest that measuring methotrexate concentrations within 24 h post-administration enhances the effectiveness of monitoring, thereby promoting rational drug use and ensuring optimal therapeutic dosing.</div><div>In summary, we have conducted a comprehensive study establishing a robust method for determining methotrexate concentrations in patient plasma. The optimized HPLC-ESI/triple method is poised for widespread application in clinical practice to monitor methotrexate therapy in pediatric patients.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1255 ","pages":"Article 124529"},"PeriodicalIF":2.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471330","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":"Evaluation of binding interaction between compounds targeting peroxisome proliferator-activated receptor γ in Nelumbinis folium using receptor chromatography and molecular dynamic simulation","authors":"Qingqing Yao ,&nbsp;Jiatai Yin ,&nbsp;Xiuli Ji ,&nbsp;Xue Li ,&nbsp;Yifan Gao ,&nbsp;Dan Lu ,&nbsp;Ying Chen ,&nbsp;Qian Li ,&nbsp;Dalong Zhi","doi":"10.1016/j.jchromb.2025.124528","DOIUrl":"10.1016/j.jchromb.2025.124528","url":null,"abstract":"<div><div>Despite considerable efforts invested in clinical trials aimed at treating obesity and enhancing the metabolic profiles of <em>Nelumbinis Folium</em>, the precise phytochemicals involved and their mechanisms of action remain unclear due to the absence of an efficient screening technique. Herein, <em>Nelumbinis Folium</em> serves as the focal point to elucidate the bioactive compounds that specifically bind to peroxisome proliferator-activated receptor γ using immobilized receptor chromatography. Following identification through liquid chromatography-mass spectrometry, the compounds were further evaluated using chromatographic techniques and molecular dynamics simulations. The results unveiled catechin and hypericin as the receptor-binding compounds present in <em>Nelumbinis Folium</em>, with hypericin exhibiting a stronger affinity and a faster dissociation rate constant compared to catechin. Molecular dynamics studies highlighted the crucial role of cysteine located at position of 285 in the receptor ligand binding domain during the initial ligand capture phase. Subsequently, Van Der Waals forces and electrostatic interactions facilitated the binding process. The calculated standard binding free energies were − 61.75 ± 2.61 kcal/mol for hypericin and − 43.19 ± 0.63 kcal/mol for catechin. Collectively, these findings provide valuable insights into receptor-drug interactions and confirm the effectiveness of immobilized receptor chromatography in screening potential lead compounds from complex systems.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1255 ","pages":"Article 124528"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463660","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":"Tissue distribution, excretion characteristics and metabolic profiling studies of oxypeucedanin in rats using liquid chromatography tandem mass spectrometry","authors":"Huixiao Duo ,&nbsp;Liyun Wang ,&nbsp;Pei Lu ,&nbsp;Xiaodan Zhang ,&nbsp;Mingcong Zheng ,&nbsp;Hanying Song ,&nbsp;Juan Zhou ,&nbsp;Wenzhuo Lei ,&nbsp;Shushu Ding ,&nbsp;Jie Jia Li ,&nbsp;Junxu Li ,&nbsp;Qing Zhu","doi":"10.1016/j.jchromb.2025.124525","DOIUrl":"10.1016/j.jchromb.2025.124525","url":null,"abstract":"<div><div>Oxypeucedanin (OPD) is a linear furanocoumarin extracted from Chinese herbs, which has been reported to exhibit various pharmacological effects such as analgesia, antitussive, anticancer and anti-inflammatory activities. In this paper, the tissue distribution, excretion and metabolism characteristics of OPD in rat was conducted in order to better understand this compound and for potential development of OPD as a medicine. We first used the established HPLC/MS/MS method to examine the plasma protein binding rate and the tissue distribution of OPD in rats after oral administration. The excretion characteristics of OPD in urine, feces and bile, as well as its metabolic profiles in plasma, urine and bile were also investigated. The results demonstrated that after OPD administration, extensive metabolism occurred in rats, involving first-pass effect and enterohepatic circulation, with significant sex differences observed in the metabolic process. The study identified eight metabolites in rats, indicating that OPD metabolism primarily occurs through oxidation, reduction, and glucuronidation. In summary, this study systematically examined the basic process of OPD in vivo, providing a robust foundation for accurately predicting the behavior, efficacy and safety of OPD in humans.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1255 ","pages":"Article 124525"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474198","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 comprehensive evaluation of a bioanalytical technique for Encorafenib and Cetuximab combination Cancer therapy by LC-MS/MS and their pharmacokinetics in plasma","authors":"Anoop Bodapati ,&nbsp;Bangaraiah Pagala ,&nbsp;Sudha Divya Madhuri Kallam","doi":"10.1016/j.jchromb.2025.124530","DOIUrl":"10.1016/j.jchromb.2025.124530","url":null,"abstract":"<div><div>The FDA authorized Encorafenib on April 8, 2020, taken along with cetuximab to treat patients (adults) with advanced metastatic colo-rectal cancers, who have a mutation of BRAF-V600E and have previously undergone therapy. No documented techniques for the simultaneous quantitation of Encorafenib and Cetuximab using LC-MS/MS was available, so a reliable, fast, and unique method was developed and validated. Method development involved optimizing chromatographic and mass spectrometric conditions to achieve high sensitivity and specificity. The method was validated per FDA guidelines, evaluating parameters such as linearity, precision, accuracy, recovery, and stability under various conditions. Mass ion pairs were tracked using multiple reaction monitoring (MRM) in positive polarity mode and the precursor to daughter ion transition <em>m</em>/<em>z</em> values for Encorafenib, Cetuximab(peptide), and Tofacitinib (internal reference) are 540.15 → 369.85, 643.34 → 653.31, and 313.17 → 221.05, respectively. The calibration curves demonstrated excellent linearity over 3.75–150 ng/mL ranges for Encorafenib and 0.25–10 ng/mL for Cetuximab. The MS² system offers a significant advantage with its ability to specifically target ions of interest. The technique was effectively employed to quantitate the levels of analytes, key pharmacokinetic parameters were assessed in rats following single-dose administration. Encorafenib exhibited a Cmax of 72.543 ng/mL, Tmax of 2 h, and T1/2 of 20 h, whereas Cetuximab showed a Cmax of 4.982 ng/mL, Tmax of 1 h, and T1/2 of 10 h. Stability studies confirmed the analytes' robustness under various conditions. These findings highlight the method's utility for accurate monitoring of pharmacokinetic parameters, essential for therapeutic drug monitoring in biological samples. It tracks drug levels drugs from administration to several hours post-dose at set intervals, enabling the evaluation of metabolism, excretion, and protein binding, which aid in the creation of treatment plans. It also facilitates routine monitoring of selected medications in clinical trials.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1255 ","pages":"Article 124530"},"PeriodicalIF":2.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471331","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":"Imatinib and norimatinib therapeutic monitoring using dried blood spots: Analytical and clinical validation, and performance comparison of volumetric collection devices","authors":"Marco Orleni ,&nbsp;Sara Gagno ,&nbsp;Eleonora Cecchin ,&nbsp;Marcella Montico ,&nbsp;Angela Buonadonna ,&nbsp;Arianna Fumagalli ,&nbsp;Michela Guardascione ,&nbsp;Fabio Puglisi ,&nbsp;Giuseppe Toffoli ,&nbsp;Bianca Posocco ,&nbsp;Erika Cecchin","doi":"10.1016/j.jchromb.2025.124526","DOIUrl":"10.1016/j.jchromb.2025.124526","url":null,"abstract":"<div><div>Therapeutic drug monitoring during imatinib treatment is recommended to optimize patient clinical outcomes. This study aimed to develop a novel LC-MS/MS method to quantitate imatinib and its active metabolite <em>N</em>-desmethyl-imatinib, in volumetric dried blood spots (DBS) using the HemaXis DB10 and Capitainer B devices. Chromatographic separation was achieved using an XTerra MS C18 column and detection occurred with a SCIEX 4000QTrap tandem mass spectrometer using electrospray positive-mode ionization. Analytical validation was successfully performed adhering to the latest guidelines. The assay was linear over the range 240–6000 ng/mL for imatinib and 48–1200 ng/mL for its metabolite, accurate (89 %–113 %) and precise (≤17 % imprecision) across a hematocrit range of 22–55 % for both devices. Recovery ranged from 84 % to 92 %, with no influence of matrix components. Stability was confirmed after at least 43 days in desiccator conditions (20 °C, ≤35 % humidity), and in conditions that mimed home-sampling. Clinical validation, conducted on 52 paired DBS and plasma samples from 28 patients, revealed that the DBS-to-plasma ratio can be used to convert DBS measurements into plasma concentrations. Bland-Altman and Passing-Bablok analyses indicated strong agreement between the estimated and actual plasma concentrations for both imatinib and its metabolite across both devices. The conversion method was further tested on an additional set of 25 to 31 samples, with 80 to 97 % of the samples falling within ±20 % difference. This study proved that DBS collected using either HemaXis DB10 or Capitainer B devices can be reliably implemented as an alternative to plasma for therapeutic drug monitoring during imatinib therapy.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1255 ","pages":"Article 124526"},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463682","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}