Journal of Chromatography B最新文献

{"title":"Scale-up of analytical IP-RP-HPLC methods for high-purity semi-preparative purification of oligonucleotides","authors":"Simonas Balčiūnas ,&nbsp;Matas Damonskis ,&nbsp;Vytautas Tamošiūnas ,&nbsp;Dennis Köhler ,&nbsp;Evaldas Naujalis ,&nbsp;Lukas Taujenis","doi":"10.1016/j.jchromb.2025.124670","DOIUrl":"10.1016/j.jchromb.2025.124670","url":null,"abstract":"<div><div>Oligonucleotides (ONs) have a wide variety of applications in molecular biology, diagnostics and biotechnology. Liquid chromatographic techniques are often used for their characterization and purification. The process of scaling up chromatographic methods for ON purification is theoretically well-understood, yet practical examples and detailed considerations are often lacking. This study addresses this gap by focusing on the scale-up of analytical ion-pair reversed-phase high performance liquid chromatography (IP-RP-HPLC) methods to the semi-preparative scale. Key properties such as linear velocity, load and gradient profiles were investigated, to ensure consistency between analytical and preparative formats. Using identical resin across different columns and a single HPLC system with two different configurations, we successfully achieved matching separation profiles between analytical and preparative scales. The scaled-up methods allowed effective purification of studied ON samples, yielding HPLC purities of 92.9 % and higher, with recoveries ranging from 94.1 % to 99.3 %. Our results demonstrate the importance of maintaining kinetic and dynamic equivalence during the scale-up process to allow efficient purification while maintaining separation achieved on the analytical scale. This study offers a comprehensive framework for scaling analytical IP-RP-HPLC methods and collecting high purity fractions, allowing further characterization of full-length products and impurities of interest.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1262 ","pages":"Article 124670"},"PeriodicalIF":2.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139262","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":"Comparison of liver bile acid profiles in chronic alcohol feeding and NIAAA binge-on-chronic alcohol feeding mouse models","authors":"Jing Feng ,&nbsp;Liqing He ,&nbsp;Xipeng Ma ,&nbsp;Xinmin Yin ,&nbsp;Eugene G. Mueller ,&nbsp;Zhanxiang Zhou ,&nbsp;Wenke Feng ,&nbsp;Craig J. McClain ,&nbsp;Xiang Zhang","doi":"10.1016/j.jchromb.2025.124650","DOIUrl":"10.1016/j.jchromb.2025.124650","url":null,"abstract":"<div><div>Alcohol-associated liver disease (ALD) is associated with disturbances in bile acid (BA) metabolism. Several mouse models have been established to mimic human ALD in the clinical setting for mechanistic investigations, and differences in BA metabolism between these models have not been systematically studied. We quantified BA alterations by liquid chromatography-mass spectrometry (LC-MS) in the livers of two widely used mouse models: the chronic Lieber-DeCarli ethanol diet (CLD) model and the National Institute on Alcohol Abuse and Alcoholism binge-on-chronic alcohol feeding (NIAAA) model, both of which aim to mimic the early stages of human ALD. Statistical analysis showed that total BA levels did not change significantly in either model. However, unconjugated BAs were elevated in both models, and glycol-conjugated BAs were significantly increased only in the NIAAA model. The deconjugation capacity of ursodeoxycholic acid (UDCA) and β-muricholic acid (β-MCA) was increased in the CLD model, whereas that of cholic acid (CA) and lithocholic acid (LCA) was increased in the NIAAA model. NIAAA mice showed increased FXR affinity, implying that the classical biosynthetic pathway of hepatic BAs was inhibited. In conclusion, although total BA levels remained unchanged in the early stages of ALD in both models, the BA composition was more altered in the NIAAA model than in the CLD model, suggesting that different ALD mouse models may exhibit divergent regulatory mechanisms for BA metabolism.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1262 ","pages":"Article 124650"},"PeriodicalIF":2.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124739","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":"Chemical identification and metabolic profiling of Tongmai granules using UHPLC-QTOF-MS-based molecular networking and modified mass defect filtering techniques","authors":"Yong-Juan Zhao ,&nbsp;Wen-Yue Zhou ,&nbsp;Lu Zhang ,&nbsp;Jia-Xiu Guo ,&nbsp;Lu-Lu Fan ,&nbsp;Yu-Ting Zhu ,&nbsp;Ying-Li ,&nbsp;Bing-Chun Yan ,&nbsp;Han-Qing Pang","doi":"10.1016/j.jchromb.2025.124669","DOIUrl":"10.1016/j.jchromb.2025.124669","url":null,"abstract":"<div><div>Ischemic stroke (IS) is a major cause of death and disability worldwide, and its complicated biological processes make developing effective treatments challenging. Tongmai granules, the famous Chinese herbal formula, was good at treating IS. However, the active compounds and their underlying mechanisms are still not well understood. To elucidate the active compounds of Tongmai granules against IS, the chemical compounds of Tongmai granules were characterized using ultra-high performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS). Using molecular networking (MN) method, a total of 89 compounds were quickly identified. Afterwards, the metabolites profiling of Tongmai granules in the middle cerebral artery occlusion/reperfusion (MCAO/R) rats' plasma and brain were conducted using UHPLC-HRMS and mass defect filtering (MDF) strategy. And 80 metabolites (25 prototypes and 55 metabolites) were characterized in plasma and brain samples. Network pharmacology and molecular docking have identified 8 active components for treating IS, including daidzein, tanshinone IIA, puerarin, cryptotanshinone, tanshinone IIb, butylidenephthalide, senkyunolide A and salvianolic acid A. These components may exert their effects through regulating TP53, SRC, and STAT3. The study provides a comprehensive characterization of Tongmai granules and insights into their therapeutic mechanisms.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1262 ","pages":"Article 124669"},"PeriodicalIF":2.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144139165","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":"Quality control in GC–MS analysis of amino acids in human urine and plasma: Possible implications for targeted and untargeted metabolomics","authors":"Alexander Bollenbach,&nbsp;Bibiana Beckmann,&nbsp;Dimitrios Tsikas","doi":"10.1016/j.jchromb.2025.124661","DOIUrl":"10.1016/j.jchromb.2025.124661","url":null,"abstract":"<div><div>In metabolomics, LC-MS(/MS) is currently used about two times more frequently than GC–MS(/MS) since about 2005, perhaps the year of appearance of metabolomics as an individual analytical approach in the life sciences. LC-MS(/MS) and GC–MS(/MS) share many common challenges in targeted and untargeted metabolomics, the Janus face of metabolomics. Especially the importance of the key issue of quality assurance (QA) and quality control (QC) has been recognized and is increasingly addressed by individual researchers and consortia. In previous work, our group has proposed a QC system for the quantitative GC–MS analysis of amino acids in human plasma samples. In the present study, we investigated the utility of such a QC approach for the quantitative (targeted) GC–MS analysis of amino acids in human urine samples by using previously validated methods. Endogenous (unlabeled) amino acids were analyzed in 10-μL aliquots of study urine samples and in QC urine samples as methyl ester pentafluoropropionyl derivatives (d₀Me-PFP) using a mixture of in-situ prepared trideuteromethyl esters for use as internal standards, which were then converted into their PFP derivatives (i.e., d₃Me-PFP). GC–MS analysis of 38 study urine samples and 8 QC urine samples was performed in the negative-ion chemical ionization (NICI) mode by selected-ion monitoring (SIM) of characteristic ions of d₀Me-PFP and d₃Me-PFP within a single run by using an oven temperature program. For direct comparison, analysis of 35 study plasma samples and 8 QC plasma samples of the same clinical study was performed. Closely comparable experimental and instrumental conditions were used in the analyses, and the same staff was involved in the entirely analytical process. Chromatographic H/D isotope effects and peak area values were determined and examined with respect to qualitative and quantitative GC and MS parameters including accuracy and precision. Study and QC plasma behaved similarly. On a molar basis, the amino acid derivatives have different peak area values. Yet, this does not affect the accuracy of the GC–MS method. Our study suggests that untargeted GC–MS metabolomics studies on amino acids in biological samples are inappropriate for quantitative GC–MS analysis. Targeted metabolomics, i.e., use of isotopologs are indispensable for reliable quantitative GC–MS analysis of amino acids in biological samples. It is reasonable to assume that our findings will also apply to other classes of analytes and types of biological samples.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1262 ","pages":"Article 124661"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116091","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":"Improvement of an ultra-high liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of eleven amino-polycyclic aromatic hydrocarbons in human urine","authors":"Haibin Li ,&nbsp;Shiwei Cui ,&nbsp;Xiaoying Zhou ,&nbsp;Qian Zhou ,&nbsp;Yanhao Zhang ,&nbsp;Shusheng Zhang ,&nbsp;Xue Tao ,&nbsp;Xin Sun","doi":"10.1016/j.jchromb.2025.124649","DOIUrl":"10.1016/j.jchromb.2025.124649","url":null,"abstract":"<div><div>Urinary amino-polycyclic aromatic hydrocarbons (amino-PAHs) are metabolites of nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) and serve as biomarkers for assessing occupational exposure to nitro-PAHs, particularly in populations exposed to diesel exhaust. Current methods for detecting urinary amino-PAHs mainly rely on liquid-liquid extraction, which has limitations in covering a wide range of nitro-PAHs and often struggles to resolve interference from isomeric compounds. This study aimed to develop a reliable UPLC-MS/MS method incorporating solid-phase extraction (SPE) pretreatment for detecting 11 amino-PAHs in urine samples from workers exposed to nitro-PAHs. Briefly, urine samples were enzymatically hydrolyzed, purified using SPE extraction, and analyzed with an optimized UPLC-MS/MS method. Effective separation of the 11 amino-PAHs was achieved using reversed-phase HSS PFP columns with a gradient elution of 0.1 % formic acid in water and acetonitrile. Improved MS/MS conditions were established to achieve sufficient sensitivity using positive ion electrospray ionization (ESI), with limits of quantification (LOQs) ranging from 0.009 to 0.378 μg L⁻¹. The method was optimized for linearity, accuracy, precision, and matrix effects, utilizing two isotopically labeled internal standards (1-Aminonaphthalene-d7 and 1-Aminopyrene-d9). This method enabled precise and accurate quantification of the 11 amino-PAHs, with a coefficient of variation (CV) of less than 11 % and recovery rates between 82.0 % and 106.9 %. The improved method provides a unique analytical approach that can be used for biomonitoring workers exposed to diesel exhaust.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1262 ","pages":"Article 124649"},"PeriodicalIF":2.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124740","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":"Preparation and utilization of an immunoadsorption column for aflatoxin B1 composed of nanobodies and pre-crosslinked agarose microspheres","authors":"Xiao Ding ,&nbsp;Shuo Wang ,&nbsp;Wei Wang ,&nbsp;Jingjing Sun ,&nbsp;Chengcheng Jiang ,&nbsp;Jianhua Hao","doi":"10.1016/j.jchromb.2025.124656","DOIUrl":"10.1016/j.jchromb.2025.124656","url":null,"abstract":"<div><div>Recent studies on immunoaffinity chromatography (IAC) columns for aflatoxin B₁ (AFB₁) have not provided a comprehensive preparation procedure or explored their capacity, reusability, and stability. In this study, we outline a preparation process for an AFB₁ immune affinity column filler (AFB₁-IAC) for extracting AFB₁ from food sources like rice, peanuts, and soybeans. Using commercially available IAC is often limited due to high costs, low capacity, slow flow rates, and poor reusability. To overcome these issues, we developed succinic anhydride (SA)-modified agarose pre-crosslinked microspheres (SA-A) activated with 1,1′‑carbonyldiimidazole (CDI). The activated microspheres were coupled with the anti-AFB₁ nanobody Nb02, creating an immunoaffinity packing called CDI-SA-A-Nb02 (D1-IAC). After verification, the results indicated that the column capacity of D1-IAC was about 4.67 times that of several commercial IAC brands. Additionally, the maximum flow rate at a pressure of 0.04 MPa was 25 % greater than specific commercial IAC, and the recovery rate remained above 80 % after being reused five times. This method is considered effective for extracting and detecting AFB₁ in food products. The preparation process for D1-IAC shows great consistency, and the column's performance is better than that of available immunoaffinity columns. This study explores using an IAC to extract and purify AFB₁, which is then quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1262 ","pages":"Article 124656"},"PeriodicalIF":2.8,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124738","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":"High-throughput screening of 311 new psychoactive substances and metabolites in wastewater by direct injection UPLC-MS/MS","authors":"Yue Xiao ,&nbsp;Shuai Yuan ,&nbsp;Ruxin Luo ,&nbsp;Ruiqin Zhu ,&nbsp;Qiongying Zheng ,&nbsp;Bin Di ,&nbsp;Ping Xiang","doi":"10.1016/j.jchromb.2025.124659","DOIUrl":"10.1016/j.jchromb.2025.124659","url":null,"abstract":"<div><div>The rapid global spread of new psychoactive substances (NPS) in recent years has become an issue in many countries. One emerging technology that can provide early warnings and assessments of drug situations is the monitoring of NPS in wastewater. In this study, we developed and optimized a high-throughput qualitative screening method based on direct injection that enabled the simultaneous detection of 311 NPS and metabolites (87 synthetic cannabinoids, 43 synthetic cathinones, 71 phenylethylamines, 10 tryptamines, 40 phencyclidines, 9 benzodiazepines, 38 fentanyls, and 13 piperazines) in wastewater. The run time for drug detection was only 16 min, and the method was validated to perform well in terms of selectivity, limit of detection (LOD), recovery, and matrix effect. Overall, 95.8 % of the targets had an LOD ≤10 ng/L and the recoveries ranged from 71.01 % to 119.88 %. The method was validated on 976 real samples from a city in China, and 32 substances were detected, with the highest detection rate for ketamine. This study provides a simple and direct analytical method for wastewater monitoring, which will aid in combating drug-related crime and maintaining social stability as new NPS continue to enter global markets.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1262 ","pages":"Article 124659"},"PeriodicalIF":2.8,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124889","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":"High-performance thin-layer chromatography combined with effect-directed assays revealed bioactivity profiles of Salvia aegyptiaca, S. verbenaca, and S. officinalis","authors":"Amira Reguigui ,&nbsp;Márton Baglyas ,&nbsp;Anna Cselőtey ,&nbsp;Mehrez Romdhane ,&nbsp;Ágnes M. Móricz","doi":"10.1016/j.jchromb.2025.124653","DOIUrl":"10.1016/j.jchromb.2025.124653","url":null,"abstract":"<div><div>The effect-directed profiling of aqueous ethanol extracts of Tunisian <em>Salvia aegyptiaca</em> and <em>Salvia verbenaca</em> aerial parts and Tunisian and Hungarian <em>Salvia officinalis</em> leaves was achieved by high-performance thin-layer chromatography (HPTLC) coupled with radical scavenging (using DPPH• free radical) and enzyme inhibitory (acetylcholinesterase, AChE) bioactivity assays. The mixture of toluene – ethyl acetate – methanol – formic acid, 11:2:6:1 (<em>V/V</em>) was used as a mobile phase for the separation of bioactive zones. The characterization of the compounds present in the active zones was performed by derivatization with aluminum chloride or natural product-polyethylene glycol (NP-PEG) reagent, and HPTLC–heated electrospray ionization-high resolution tandem mass spectrometry (HPTLC–HESI-HRMS/MS). Compounds in the nine antioxidant zones could be characterized by derivatization as phenolic compounds and tentatively identified by MS as caffeic acid derivatives, or flavonoid glycosides or glucuronides. Rosmarinic acid and luteolin 7-<em>O</em>-glucuronide were detected in <em>S. aegyptiaca</em> and <em>S. officinalis</em> extracts, while apigenin 7-<em>O</em>-glucuronide and luteolin 7-<em>O</em>-glucoside were identified in <em>S. aegyptiaca</em> and <em>S. verbenaca</em>. The co-presence of an unknown caffeic acid derivative, hispidulin 7-<em>O</em>-glucuronide and luteolin 7-<em>O</em>-glucoside was proved within a single zone of <em>S. officinalis</em> extract. Additionally, an unknown rosmarinic acid derivative and an unknown luteolin derivative were detected in <em>S. officinalis</em> and <em>S. verbenaca</em>, respectively. These compounds exhibited weak AChE inhibitory activity, with luteolin 7-<em>O</em>-glucuronide demonstrating the strongest effect.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1261 ","pages":"Article 124653"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090218","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":"Screening and identification of AChE inhibitors from walnut kernel by a combination of bio-affinity ultrafiltration, AChE-functionalized magnetic nanoparticles and UPLC-Q-exactive orbitrap MS","authors":"Yong Ding ,&nbsp;Yu-tong Song ,&nbsp;Ze-xu Yang ,&nbsp;Xia-jing Xu ,&nbsp;Qing-zhu Zhang ,&nbsp;Dong-mei Wang ,&nbsp;Ying-ni Pan ,&nbsp;Kun Ren ,&nbsp;Shu-meng Ren ,&nbsp;Xiao-qiu Liu","doi":"10.1016/j.jchromb.2025.124657","DOIUrl":"10.1016/j.jchromb.2025.124657","url":null,"abstract":"<div><div>Acetylcholinesterase (AChE) is widely concerned as a hotspot target for the treatment of Alzheimer's disease (AD). This study aimed to screen AChE inhibitors from walnut kernel (WK) through the techniques combined of bio-affinity ultrafiltration, AChE-functionalized magnetic nanoparticles and UPLC-Q-Exactive Orbitrap MS. The results showed that WK extract improved acetylcholine level and reduced AChE level in the hippocampus and cortex of AD mice with kidney yang deficiency. AChE inhibition experiment showed WK extract has the best activity with IC₅₀ values at 1.310 mg/mL. Bio-affinity ultrafiltration combined with UPLC-Q-Exactive Orbitrap MS screened out 3 active compounds, including ellagic acid 4-<em>O</em>-xyloside, ellagic acid (EA) and glansreginin A. In order to avoid false positive results, AChE-functionalized magnetic nanoparticles combined with HPLC was used to ligand fish again, and EA was fished. And the IC₅₀ value of EA on AChE was 1.486 mg/mL. Molecular docking showed EA had the calculated binding energies at −8.468 kJ/moL with AChE, and could interact with the amino acid residues of ASP 74, TYR 133 and GLU 202 via hydrogen bonds and had the pi-pi bonds with TRP 86. The developed ligand fishing method is simple and efficient for screening potential AChE inhibitors from medicinal plant.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1261 ","pages":"Article 124657"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144098874","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 an LC-MS/MS method for simultaneous determination of XZP-3287(bireociclib) and its metabolites in human plasma, and its clinical pharmacokinetics application","authors":"Bohan Liang ,&nbsp;Yanjie Li ,&nbsp;Lingmei Xu ,&nbsp;Li Wang ,&nbsp;Quankun Zhuang ,&nbsp;Shiqi Dong ,&nbsp;Huirong Fan","doi":"10.1016/j.jchromb.2025.124658","DOIUrl":"10.1016/j.jchromb.2025.124658","url":null,"abstract":"<div><div>XZP-3287(bireociclib) is a novel and selective inhibitor of the cell cyclin-dependent kinases 4/6 (CDK4/6), which is primarily employed for the treatment of breast cancer in clinical trials. In this study, a novel and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of XZP-3287 and its metabolites XZP-5286, XZP-3584 and XZP-5736 in human plasma in accordance with international conference on harmonization of technical requirements for registration of Pharmaceuticals for Human use (ICH) guideline R3 (M10) guideline. The multiple reaction monitoring mode (MRM) of mass spectrometer was used and all compounds were monitored in electrospray ionization (ESI+) mode. The correlation coefficients (R²) of all calibration curves for linear regression were greater than 0.99. The intra- and inter-day precision of XZP-3287 and its metabolites XZP-5286, XZP-3584 and XZP-5736 were determined to be 5.2 %–5.5 %, 14.9 %–10.1 %, 6.9 %–13.8 % and 7.3 %–5.6 %, and their accuracy were determined to be 5.2 %–6.0 % 6.9 %–4.4 %, 11.1 %–5.0 % and 7.4 %–5.6 %, respectively. In conclusion, a method for the simultaneous detection of the pharmacokinetic profiles of XZP-3287 and its metabolites in human plasma had been successfully developed. The results demonstrated the efficacy, sensitivity, and reliability of this method</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1261 ","pages":"Article 124658"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090217","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}