{"title":"Corrigendum to \"Pharmacokinetic and tissue distribution study of pectolinarigenin in rats using UPLC-MS/MS\" [J. Chromatogr. B 1247 (2024) 124344].","authors":"Yingying Pan, Zihan Tan, Ping Liu, Aixia Yang, Lin-Lin Chen","doi":"10.1016/j.jchromb.2024.124366","DOIUrl":"10.1016/j.jchromb.2024.124366","url":null,"abstract":"","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":" ","pages":"124366"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581352","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 of ESR2-targeted anti-postmenopausal osteoporosis chemistry from Rehmanniae Radix Preparata based on affinity ultrafiltration with UPLC-QE-Orbitrap-MS.","authors":"Shuo Wang, Yawen Li, Nanxi Zhang, Peitong Wu, Xueqin Feng, Xiaochen Gao, Jiaming Shen, Wanjie Liu, Wei Feng, Jiaming Sun","doi":"10.1016/j.jchromb.2024.124419","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124419","url":null,"abstract":"<p><p>Rehmanniae Radix Preparata, a processed form of the traditional Chinese medicinal plant Rehmannia glutinosa Libosch, has long been valued for its medicinal properties and use as a food. It is notably effective in treating postmenopausal osteoporosis. This study utilized C18 to separate and purify different concentrations of its eluent streams. MC3T3-E1 cells were utilized to identify the optimal ESR2 activity fraction from various concentrations of Rehmanniae Radix Preparata, using osteoprotegerin (OPG) as an indicator. A single-target affinity ultrafiltration method was created, combining ESR2 affinity ultrafiltration with liquid chromatography-mass spectrometry (LC-MS). Molecular docking validated the interaction mechanism between small molecule ligands and ESR2 protein. These ligands were then tested in MC3T3-E1 cells to assess survival rate, OPG content, and alkaline phosphatase (ALP) activity, an osteogenic differentiation marker. The study showed that Radix Rehmanniae Praeparata effectively combats PMOP, and the combined method of single-target-affinity ultrafiltration-LC-MS with molecular docking offers a robust approach for identifying its anti-PMOP compounds.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124419"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845420","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 a quantification method for direct oral anticoagulants from capillary blood using volumetric absorptive microsampling and online SPE-LC-MS.","authors":"Patrick Opitz, Isabel Waltering, Georg Hempel","doi":"10.1016/j.jchromb.2024.124423","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124423","url":null,"abstract":"<p><p>The number of prescriptions for new direct oral anticoagulants (DOACs) apixaban, edoxaban, rivaroxaban and dabigatran has increased exponentially in recent years, increasingly replacing the old gold standard, vitamin-K-antagonists. Due to their wide therapeutic range, therapeutic drug monitoring (TDM) is not required, although it has been proven that this could significantly reduce side effects. In order to develop a cost-efficient and simple method for the simultaneous detection of the DOACs and phenprocoumon, a new technology for sample preparation from capillary blood in the ambulant sector named VAMS® was integrated and an LC-MS detector with on-line solid phase extraction (SPE) applying a Turboflow HTLC Cyclone<sup>TM</sup> 1.0x50 mm column was used. The mobile phase consisted of methanol with water (3/97 v/v) and 0.1 % ammonia solution with a flow rate of 2.5 mL/min. For the chromatographic separation, a Phenomenex LTD Kinetex 2.6 µm C18 100 Å, 100x3.0 mm column with a flow rate of 0.3 mL/min in gradient mode was utilized. The mobile phase consisted of acetonitrile, water and formic acid (A: 10:90:0.1 v/v and B: 95:05:0.1 v/v). The method was fully validated in the therapeutic range of the substances according to current guidelines. The LLOQ ranged from 3.5 µg/L for rivaroxaban to 88 µg/L for phenprocoumon and the intra-day and inter-day precision was less than 13 % and 12 %, while the accuracy was within a range of 85.7-113 % and 88.7-106 %, respectively. Samples could be stored in the Mitra® devices for at least seven days at room temperature except of dabigatran. Because the Mitras® were used, exactly 10 µL of blood could be drawn and no significant haematocrit effect was observed. A reliable, simple and cost-effective extraction and analysis LC-MS method could be developed and validated. This method is therefore applicable in ambulatory care.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124423"},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833561","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}
Şule Temiz, Songül Ulusoy, Halil İbrahim Ulusoy, Esra Durgun, Ümmügülsüm Polat, Gökhan Sarp
{"title":"Synthesis and use of new magnetic adsorbent for sensitive, practical and simultaneous analysis Ibuprofen and Ketoprofen molecules in urine samples.","authors":"Şule Temiz, Songül Ulusoy, Halil İbrahim Ulusoy, Esra Durgun, Ümmügülsüm Polat, Gökhan Sarp","doi":"10.1016/j.jchromb.2024.124404","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124404","url":null,"abstract":"<p><p>A new sample preparation and determination method, including HPLC-DAD analysis after Magnetic Solid Phase Extraction (MSPE), was developed to monitor the trace amounts of two types of nonsteroidal anti-inflammatory drugs (NSAIDs), Ibuprofen (IBP) and Ketoprofen (KP). In the proposed method, IBP and KP analytes were extracted from newly synthesized magnetic-based sorbent in a pH 4.0 buffer medium and enriched by desorbing again with ethanol to a smaller volume before chromatographic determinations. The samples were filtered and transferred to HPLC vials before analysis. The experimental variables were optimized step by step such as adsorption time, desorption solvent, pH, etc. After preconcentration of IBP and KP molecules by MSPE, determination of target molecules was carried out by isocratic elution of 30 % Methyl alcohol, 40 % Trifluoro Acetic Acid (TFA) (0.1 %, v:v), 30 % Acetonitrile. By using optimized conditions, the detection limits of target molecules were calculated as 3.43 ng mL<sup>-1</sup> and 3.48 ng mL<sup>-1</sup> for IBP and KP, respectively. The triplicate measurements made with model solutions containing 100 ng mL<sup>-1</sup> of target molecules, RSD %values were found below 3.50 %. The developed method was successfully applied to synthetic urine and pooling urine samples. Finally, the practicality and suitability for green analytical chemistry of the proposed method was evaluated by using Blue Applicability Grade Index (BAGI) and Green Analytical Procedure Index (GAPI).</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124404"},"PeriodicalIF":2.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845435","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":"Effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban in vivo.","authors":"Zhi Wang, Zefang Yu, Lingzhi Fang, Jing An, Chaojun Xue, Xin Zhou, Xiao Li, Ying Li, Zhanjun Dong","doi":"10.1016/j.jchromb.2024.124425","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124425","url":null,"abstract":"<p><p>Furmonertinib, a third generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), is used for non-small cell lung cancer (NSCLC). Rivaroxaban and apixaban are direct oral anticoagulants (DOACs) used for venous thromboembolism (VTE), which is a frequent comorbid with NSCLC. They are substrates of CYP3A4, P-gp and BCRP, whereas furmonertinib is an inhibitor of P-gp and BCRP. This study aimed to disclose the extent of effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban. Rats were divided into four groups (n = 6) that received rivaroxaban (group 1), furmonertinib and rivaroxaban (group 2), apixaban (group 3), furmonertinib and apixaban (group 4). The concentrations of drugs were measured by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Furmonertinib increased the C<sub>max</sub> and AUC<sub>0-t</sub> of rivaroxaban by 1.66 and 2.07-fold, whereas decreased the CL<sub>z</sub>/F by 1.70-fold and V<sub>z</sub>/F 1.27-fold. Furthermore, furmonertinib caused similar changes in apixaban pharmacokinetics. The pharmacokinetic results suggest that it is essential to alert the effect of furmonertinib on the pharmacokinetics of rivaroxaban or apixaban in clinical practice.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124425"},"PeriodicalIF":2.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826959","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":"Quantification of gimeracil, tegafur, and 5-FU in human plasma via LC-MS/MS with a simplified pretreatment using flow-through extraction.","authors":"Motozumi Ando, Norio Watanabe, Riko Seike, Saori Gocho, Shoko Maeda, Masami Inagaki, Masami Kawahara","doi":"10.1016/j.jchromb.2024.124424","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124424","url":null,"abstract":"<p><p>Gimeracil, a component in S-1 (an oral anticancer agent comprising tegafur, a prodrug of 5-fluorouracil (5-FU), potassium oxonate, and gimeracil), inhibits metabolic enzymes, thereby impeding 5-FU degradation. Therefore, the blood level of gimeracil is closely associated with the disposition of 5-FU, and quantification of gimeracil can provide important information if a case shows an inappropriate 5-FU blood concentration. Nevertheless, methods for quantifying gimeracil in human plasma are rarely reported. Herein, we aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying gimeracil, in addition to tegafur and 5-FU, levels in human plasma using a clinically applicable simplified pretreatment process and faster elution time. Hence, an acetamide-functionalized monolith silica disk-packed spin column was used to extract gimeracil and internal standard (IS; nicotinamide), whereas diatomaceous earth-based solid phase for liquid-liquid extraction was used to extract tegafur, 5-FU, and IS (5-chlorouracil) from plasma. Each extract was analyzed within 4 min of elution via LC-MS/MS using a shared LC column and mobile phase. Accuracy and precision analyses indicated lower limits of quantification of 5, 10, and 2 ng/mL for gimeracil, tegafur, and 5-FU, respectively. The calibration curves showed good linearity between 5 and 500 ng/mL for gimeracil, 10 and 5000 ng/mL for tegafur, and 2 and 1000 ng/mL for 5-FU. We confirmed that the levels of all analytes in the plasma of patients with cancer undergoing S-1-inclusive therapy were within the calibration range for each analyte. Thus, this newly developed quantification method is likely to be useful for optimization of S-1 therapy.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124424"},"PeriodicalIF":2.8,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845406","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":"Interaction of lysozyme with solid supports cryogels containing imidazole functional group.","authors":"Radwan Ahmed Tarish Abdullah, Koray Şarkaya","doi":"10.1016/j.jchromb.2024.124405","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124405","url":null,"abstract":"<p><p>This paper details the preparation of acrylamide-based supermacroporous cryogels and their application in removing lysozyme from aqueous solutions. N-Vinyl imidazole was copolymerized with acrylamide as a comonomer to impart pseudo-specificity to the cryogels, forming poly(AAm-VIM) cryogel. Characterization studies to assess the physical and chemical properties of the synthesized cryogels involved swelling tests, Fourier Transform Infrared Spectroscopy (FTIR), elemental analysis, Field Emission Scanning Electron Microscopy (FESEM), and Thermogravimetric Analysis (TGA-DTA). To ascertain the optimal conditions for the adsorption process, pH 9.0 (TRIS buffer) was selected for lysozyme adsorption, using the parametres such as initial concentration screening, ionic strength, temperature, and column flow rate. The Langmuir and Freundlich isotherm models were analyzed to assess the adsorption parameters mathematically. The regression coefficient results indicated that lysozyme adsorption aligned more closely with the Langmuir isotherm model. The adsorption process is considered to be thermodynamically physical and spontaneous. SDS-PAGE analysis assessed the purity of lysozyme isolated from an aqueous solution using a poly(AAm-VIM) cryogel column. The inertness and regeneration capacity of poly(AAm-VIM) cryogel affinity columns were assessed using reusability studies conducted during the adsorption-desorption cycle.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124405"},"PeriodicalIF":2.8,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811499","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":"Study on the protective mechanism of Xuemaitong Capsule against acute myocardial ischemia rat based on network pharmacology and metabolomics.","authors":"Jialu Zou, Shizhong Zhang, Xiaohong Zhang, Lijuan Xiong, Xuan Chen, Yanmei He, Cancan Duan, Jianyong Zhang","doi":"10.1016/j.jchromb.2024.124373","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124373","url":null,"abstract":"<p><strong>Background: </strong>Xuemaitong Capsule (XMT) is a widely recognized traditional Miao medicine extensively utilized in Chinese clinical settings. Previous studies have demonstrated XMT protective effects against acute myocardial ischemia (AMI). However, the mechanism by which XMT provides protection to AMI rats is yet to be fully understood.</p><p><strong>Aim of the study: </strong>The purpose of this study was to investigate the protective mechanism of XMT on AMI rats through network pharmacology, traditional pharmacodynamics and metabolomics.</p><p><strong>Material and methods: </strong>The components and potential targets of XMT were identified through the application of traditional Chinese medicine system pharmacology and traditional Chinese medicine molecular mechanism bioinformatics analysis tools. We constructed herb-composition-target networks and analyzed protein-protein interaction (PPI) networks. The potential mechanism was explored by pathway enrichment analysis. Subsequently, the AMI model was constructed by ligation of the anterior descending branch of the left coronary artery, and XMT protective effects on AMI rats were evaluated by analyzing the myocardial enzyme profiles, electrocardiograms(ECG), Triphenyltetrazolium chloride(TTC) staining, and Hematoxylin-Eosin (HE) staining in AMI rats. Metabolomics based on UHPLC-Q-Exactive Orbitrap MS was used to observe the protective effect of XMT on the serum metabolic profile of AMI, and multivariate statistical analysis further revealed the differential patterns of metabolites after XMT treatment. Finally, integrated pathway analysis was carried out to reveal the biological metabolic mechanism.</p><p><strong>Results: </strong>A total of 392 active components of XMT acted with 624 targets for treating AMI. Pathway enrichment analysis revealed that XMT could treat AMI through TNF, MAPK and PI3K-Akt signaling pathways. Further, XMT could effectively prevent ST-segment elevation in the ECG, reduce the size of myocardial infarction, decrease cardiac weight index and cardiac enzyme levels, and mitigate histological damage in the hearts of AMI rats. In addition, XMT callback 117 metabolites and four metabolic pathways, including taurine and hypotaurine metabolism, phenylalanine metabolism, pyrimidine metabolism and retinol metabolism. Through integrating network pharmacology and metabolomics, we explored the biological mechanism by which XMT treats AMI. It was speculated that the mechanism of XMT is to regulate TNF signaling, PI3K-Akt pathway and MAPK signaling pathway, and participate in cell apoptosis, oxidative stress, immune and inflammatory reaction and other biological processes.</p><p><strong>Conclusion: </strong>XMT plays a protective role in AMI rats by regulating multiple metabolic biomarkers, multiple targets and pathways. Therefore, XMT may provide a potential strategy for the treatment of AMI.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124373"},"PeriodicalIF":2.8,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790813","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":"Intestinal microbiota-mediated serum pharmacochemistry reveals hepatoprotective metabolites of Platycodonis Radix against APAP-induced liver injury.","authors":"Yuan-Han Zhong, Xi-Wa Wu, Xin-Yu Zhang, Shou-Wen Zhang, Yan Feng, Xue-Mei Zhang, Bing-Bing Xu, Guo-Yue Zhong, Hui-Liang Huang, Jun-Wei He, Jin-Xiang Zeng, Jian Liang","doi":"10.1016/j.jchromb.2024.124395","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124395","url":null,"abstract":"<p><p>The urgent need for new medications that regulate CYP2E1, CASP3, Nrf2, HO-1, TLR2, TLR4, STAT3, and NF-κB activities is paramount for the treatment of drug-induced liver injury (DILI), particularly from acetaminophen (APAP). Previous studies have suggested that platycosides of Platycodonis Radix exhibits hepatoprotective properties against APAP-induced liver injury (AILI), and their serum metabolites may be the effective agents. As the identify the serum metabolites of platycosides is a huge challenge, the mechanism whether platycosides exert effects through the serum metabolites regulating those targets still remain unclear. In this study, we propose a novel method termed intestinal microbiota-mediated serum pharmacochemistry (IMSP) to identify the serum metabolite profile of platycosides, using deglycosylated platycosides as template molecules. Our results identified a total of 44 prototype platycosides in the total platycosides fraction of Platycodonis Radix (PF). In rat serum, we identified 12 prototype platycosides and 45 metabolites derived from the 44 platycosides. Furthermore, our findings indicate that all 44 platycosides can enter the serum in the form of metabolites. The presence of these metabolites in serum is closely related to their oral bioavailability and the content of the prototypes. The in vivo animal experiments showed that the PF possessed significant anti-AILI effects and CYP2E1, CASP3, Nrf2, HO-1, TLR2, TLR4, STAT3, and NF-κB p65 regulation activities. And the in vitro cell experiments and molecular docking analyses further demonstrated that the hepatoprotective effects were mainly ascribed to the serum metabolites, which regulating targets of CYP2E1, CASP3, Nrf2, HO-1, TLR2, TLR4, STAT3, and NF-κB p65. Additionally, the activities of these metabolites are closely associated with their structures. In summary, the IMSP method significantly enhances the ability to identify platycoside metabolites in serum, reveals that all platycosides may contribute to anti-AILI activity through their metabolites, PF and some of these metabolites are promising candidate compounds for developing new medications with anti-AILI effects for the first time.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124395"},"PeriodicalIF":2.8,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790811","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}
Zeyu Wang, Pingming Tang, Caixia Dou, Jiale Shen, Ni Peng, Yao Li, Ju Wang, Xiaoyan Chen
{"title":"Quantification of crisugabalin (HSK16149) in biological matrix by LC-MS/MS method: An application to rat pharmacokinetic and tissue distribution studies.","authors":"Zeyu Wang, Pingming Tang, Caixia Dou, Jiale Shen, Ni Peng, Yao Li, Ju Wang, Xiaoyan Chen","doi":"10.1016/j.jchromb.2024.124396","DOIUrl":"https://doi.org/10.1016/j.jchromb.2024.124396","url":null,"abstract":"<p><p>Crisugabalin (HSK16149), a novel VGCC α2δ ligand, has been approved for the treatment of adult diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN). In this study, an LC-MS/MS method was developed for the determination of crisugabalin in rat plasma and tissues homogenate. Samples were extracted by protein precipitation and separated on a Hypersil GOLD aQ column with methanol and 2 mM ammonium acetate in water containing 0.1 % formic acid as mobile phase. Crisugabalin and its internal standard HSK7891 were ionized by electrospray ionization source and detected by multiple reaction monitoring with transitions of m/z 210.9 → 134.4 and m/z 246.0 → 129.3. Over the range of 0.0100-10.0 μg/mL, the selectivity, linearity, precision and accuracy, matrix effect, stability, recovery and dilution integrity of crisugabalin were validated in rat plasma. Validation was also performed in rat liver homogenate at concentrations ranging from 0.0200-20.0 μg/g. The method was then successfully applied to determine the pharmacokinetics and tissue distribution of crisugabalin. In rats, orally administered crisugabalin was completely and rapidly absorbed with a peak time of about 0.57 h, and was mainly distributed to kidney, bladder and liver tissues. Crisugabalin exhibited linear pharmacokinetics over the oral dose range of 3-30 mg/kg.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124396"},"PeriodicalIF":2.8,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790812","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}