{"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":"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":"2025-01-15","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":"Optimization of liquid chromatography and mass spectrometry parameters based on LC-QQQ: A case study on lysinoalanine.","authors":"Shaoke Zhou, Yimiao Xia, Lihua Hao, Yuanjun Gao, Caifang Zhang","doi":"10.1016/j.jchromb.2024.124427","DOIUrl":"10.1016/j.jchromb.2024.124427","url":null,"abstract":"<p><p>Lysinoalanine (LAL), commonly formed in high-protein foods, raises concerns due to its nephrotoxicity and potential reduction in nutritional properties, making its accurate detection crucial for food safety. Liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ) plays a pivotal role in the quantification of compounds, and its accuracy and sensitivity are significantly influenced by specific liquid chromatography (LC) and mass spectrometry (MS) parameters. However, the procedure and considerations for LC and MS parameters optimization have often not been discussed in depth in existing literature. Therefore, this study used LAL as a model compound to systematically optimize the key LC and MS parameters using LC-QQQ. The optimized MS parameters were as follows: parent ion m/z-234.2, capillary voltage-3.5 kV, cone voltage-30 V, desolvation temperature-500 °C, daughter ion m/z-84.2, and collision voltage-20 V. The optimized LC parameters were as follows: buffer-0.1 % formic acid (v/v), column, Polaris 3 Amide-C18 (150 × 3 mm, 3 μm). Under these optimized conditions, the limit of detection (LOD) for LAL was detected as 13 ng/mL in multiple reaction monitoring mode, which is considerably lower than the 125 ng/mL detected by LC-QQQ and marginally lower than the 15.23 ng/mL detected by LC-quadrupole Exactive Orbitrap MS reported in previous studies. Additionally, this study elucidates the critical factors to be considered when selecting LC and MS parameters, providing valuable insights into the detection of other compounds using LC-QQQ.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124427"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870650","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":"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":"2025-01-15","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":"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":"2025-01-15","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}
{"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":"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":"2025-01-15","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}
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":"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":"2025-01-15","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":"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":"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":"2025-01-15","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":"Exploring the potential anti-COPD ingredients and mechanisms of the Qingfei decoction based on UHPLC-HRMS, network pharmacology and transcriptomic analysis.","authors":"Tong Zhang, Zhuoqian Guo, Tao Ma, Shanlan Li, Ziqi Dai, Yujin Luo, Feng Gao, Qi Zeng, Jihui Lu, Junshuai Wang, Yongli Liu, Bing Xu, Haimin Lei","doi":"10.1016/j.jchromb.2024.124420","DOIUrl":"10.1016/j.jchromb.2024.124420","url":null,"abstract":"<p><p>Qingfei Decoction (QFD) is recognized as one of the 100 classic prescriptions by the National Administration of Traditional Chinese Medicine of China and is widely used for the treatment of pulmonary diseases. Chronic obstructive pulmonary disease (COPD) is a common respiratory condition primarily characterized by airway obstruction. It's necessary to examine the therapeutic effect of QFD in the treatment of COPD and elucidate its potential effective components, targets, and pathways. This study utilized UHPLC coupled with HRMS to identify the chemical constituents of QFD, resulting in the qualitative analysis of 68 compounds. Network pharmacology predicted 30 gene targets, including IL6, AKT1, and EGFR, and revealed 45 compounds, including ruscogenin, schisandrin A, and esculetin that may contribute to its therapeutic effects on COPD. Subsequently, an elastase-induced COPD mouse model was employed to evaluate the efficacy of QFD. The effects of QFD were assessed through hematoxylin and eosin (H&E) staining, periodic acid-Schiff (PAS) staining, and real-time quantitative polymerase chain reaction (RT-qPCR) on lung tissues. Transcriptomic analysis indicating QFD treatment of COPD primarily acted on the IL-17 signaling pathway, which was consistent with the network pharmacology results. Furthermore, RT-qPCR, immunofluorescence, and western blot demonstrated reduced mRNA and protein expression levels of TRAF3IP2, TRAF6, IL17, and TNFα. These findings confirmed that QFD effectively reduced inflammation, likely by down-regulating the IL-17 signaling pathway, thereby treating COPD.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124420"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862789","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}
Katie A Walker, Justin N Vignola, Trinity K Rudd, C Linn Cadieux, Robert C diTargiani
{"title":"Development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the quantification of oximes in KIKO mouse plasma.","authors":"Katie A Walker, Justin N Vignola, Trinity K Rudd, C Linn Cadieux, Robert C diTargiani","doi":"10.1016/j.jchromb.2024.124426","DOIUrl":"10.1016/j.jchromb.2024.124426","url":null,"abstract":"<p><p>Chemical warfare nerve agents (CWNAs) are potent and irreversible inhibitors of acetylcholinesterase (AChE). Oxime reactivators are an important part of the standard treatment for CWNA exposure as they can reactivate inhibited AChE. Evaluating the oxime candidates of interest in biological samples requires analytical detection methods and oxime reactivators as a class of compounds have historically been notoriously difficult to isolate, detect and analyze in an analytical laboratory, and there are currently no sensitive or robust analytical detection methods in the literature. The goal of this study was to develop reliable and robust novel extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods to detect and quantitate 2-PAM, HI-6, HLö-7, and MMB-4 in a human AChE knock-in, mouse carboxylesterase knock-out (KIKO) mouse in vivo model. This study identified an LC column that achieved retention for all four oxime compounds which is a major advancement over past oxime methods. A unique extraction and chromatographic method was developed for each oxime. The developed methods were sensitive down to 0.5 ng/mL for 2-PAM, 50 ng/mL for HI-6, and 15 ng/mL for both HLö-7 and MMB-4. These methods were validated to meet the Food and Drug Administration (FDA) bioanalytical method validation requirements under Good Laboratory Practice (GLP) conditions. The 4 methods were validated for performance by assessing linearity, sensitivity, precision, accuracy, selectivity, specificity, carryover, extraction recovery, dilution analysis, and stability.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124426"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870613","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}
Xiaoyang Liu, Bo Li, Shu Li, Xiaoxue Wang, Xudong Kong, Yue Chen, Qian Zhang, Jun Duan, Wenqian Chen, Pengmei Li
{"title":"Simultaneous determination of three β-Lactam/β-lactamase inhibitor combinations in critically ill patients by UPLC-MS/MS.","authors":"Xiaoyang Liu, Bo Li, Shu Li, Xiaoxue Wang, Xudong Kong, Yue Chen, Qian Zhang, Jun Duan, Wenqian Chen, Pengmei Li","doi":"10.1016/j.jchromb.2024.124431","DOIUrl":"10.1016/j.jchromb.2024.124431","url":null,"abstract":"<p><p>β-Lactam/β-lactamase inhibitors (BL/BLIs) are widely used in critically ill patients. Recent research has shown the importance of therapeutic drug monitoring (TDM) of BLs, but few studies have highlighted the importance of detecting BLIs in critically ill patients. In our laboratory, we have developed and validated a simple and robust method for the determination of ceftazidime, cefoperazone, piperacillin, avibactam, sulbactam and tazobactam in human plasma by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Sample preparation was by protein precipitation of 100 µL of sample, followed by chromatographic separation on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm) and mass spectrometric detection using a SHIMADZU 8050CL in multiple reaction monitoring (MRM) mode. The method was fully validated for selectivity, carry-over, linearity, lower limit of quantification, matrix effect, extraction recovery, stability and dilution integrity. The results of the TDM could provide feedback to clinicians and allow timely adjustment of dosing regimens in critically ill patients. The method is suitable for routine TDM and has been successfully applied to the clinical determination of 81 plasma concentrations in 44 patients.</p>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1251 ","pages":"124431"},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890995","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}