JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2025
·
IF 2.8
Bohan Liang,Yanjie Li,Lingmei Xu,Li Wang,Quankun Zhuang,Shiqi Dong,Huirong Fan
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 (R 2 ) 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
研究领域:
药物分析
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临床药理学
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肿瘤学
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质谱分析
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药物代谢
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生物分析化学
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DOI
PubMed
高影响因子
JOURNAL OF MASS SPECTROMETRY
·
2026
·Vol. 61
·期 8
·e70088
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IF 2.1
Liping Yang,Bingling Gao,Tao Yang,Liping Tang,Ying Kan,Keqi Sun,Peng Xiao
Dehydroepiandrosterone sulfate (DHEAS), a crucial steroid hormone for adrenal function and pubertal development, is highly associated with related diseases. This study aims to develop and validate an isotope dilution liquid chromatography tandem mass spectrometry (ID-LC–MS/MS)-based candidate reference measurement procedure (cRMP) for quantifying serum DHEAS. Serum samples were prepared by protein precipitation with acetonitrile and separated on a reversed phase column. Assay validation was conducted under the guidance of standard documents, including C62-A, EP6-A, EP10-A3, and C50-P endorsed by the Clinical and Laboratory Standards Institute (CLSI). The cRMP was established and proven to be highly specific without significant matrix effect and able to accurately quantify DHEAS in human serum. The intra-assay and inter-assay imprecision ranged from < 0.1 to 1.0% and from 1.0 to 1.1%, respectively. Trueness was assessed by recovery rate from 99.6 to 101.2%. The limit of detection (LoD) was 0.270 nmol/L, and the lower limit of the measuring interval (LLMI) was 12.1 nmol/L. A linear correlation ranged from 7.60 to 41 858 nmol/L was observed with a correlation coefficient > 0.999. R 2 value of linear regression analysis between this method and clinical immunoassays was ≥ 0.990. The relative expanded uncertainty was 1.5%–2.5% over the concentration range of 12.1–33 043 nmol/L. This study developed an ID-LC–MS/MS-based cRMP, which provided high specificity, trueness, and precision for serum DHEAS quantification, contributing to the DHEAS measurement standardization and traceability.
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PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2026
·
IF 4.1
Guan Xinhui,Zhang Yuying,Ma Xiaoqiao,Wang Haiyan,Qiao Xiaoqiang,Gu Xiaofei
Comprehensive characterization of exosomal phospholipids is essential for understanding cancer-associated metabolic alterations and discovering potential biomarkers, but remains challenging due to their extensive structural diversity and the limited selectivity and coverage of conventional liquid chromatography-tandem mass spectrometry (LC-MS/MS) approaches. In this study, an ionic liquid-functionalized styrene-maleic anhydride copolymer brush stationary phase (Sil-BHHICl) was developed and integrated into an offline two-dimensional (2D) LC-MS/MS platform for comprehensive exosomal phospholipid profiling. The Sil-BHHICl stationary phase exhibited a hydrophilic interaction/reversed-phase mixed-mode retention mechanism and provided enhanced selectivity toward phospholipids, enabling efficient separation at both the phospholipid-class and molecular-species levels. The developed analytical platform enabled comprehensive profiling of plasma-derived exosomal phospholipids, resulting in the identification of 274 molecular species belonging to 10 phospholipid classes. Lipidomic analysis of plasma exosomes from breast cancer patients and healthy controls revealed distinct phospholipid alterations associated with breast cancer and identified five candidate biomarkers, among which LysoPC-O (16:0) exhibited the strongest discriminatory ability. Pathway enrichment analysis further indicated that the altered phospholipids were predominantly associated with glycerophospholipid metabolism, suggesting extensive lipid metabolic remodeling in breast cancer. Overall, this study establishes a mixed-mode chromatographic platform for high-coverage exosomal phospholipid profiling and demonstrates its potential for lipidomics-based biomarker discovery and investigation of disease-associated metabolic alterations. Graphical abstract
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高影响因子
CLINICA CHIMICA ACTA
·
2026
·
IF 4.1
Xin-Yu Wu,Xiao-Kang Fu,Ao Li,Wei Zhang,Han-Peng Jiang,Na An,Quan-Fei Zhu,Shao-Ting Wang,Yu-Qi Feng
Background Therapeutic drug monitoring (TDM) of tacrolimus requires accurate, high-throughput methods, but conventional liquid chromatography–tandem mass spectrometry (LC-MS/MS) is limited by lengthy run times and complex sample preparation. Methods We developed a chromatography-free assay for quantification of tacrolimus in whole blood by integrating cold-induced phase separation with acoustic ejection mass spectrometry (AEMS). This workflow only requires less than 10 μL of whole blood, eliminates centrifugation, and enables direct nanoliter-scale injection into the mass spectrometer. The AEMS assay performance was validated in accordance with CLSI C62-A and ICH M10 guidelines using 62 patient samples and matrix-matched calibrators, demonstrating its suitability for high-throughput therapeutic drug monitoring. Results The AEMS assay exhibited excellent linearity (0.5–50 μg/L; R 2 = 0.9987), with a lower limit of quantification of 0.5 μg/L, which was well below clinically relevant trough concentrations. Accuracy (93.3%–100.1%) and precision (intra-day RSD: 3.7%–11.3%; inter-day RSD: 2.3%–12.4%) met regulatory acceptance criteria. Results showed strong concordance with routine LC-MS/MS (Spearman ρ = 0.972; Passing–Bablok slope = 1.100 [95% CI: 1.026–1.177]). The total analysis cycle time was less than 3 s per sample, enabling a throughput exceeding 1000 samples per hour theoretically. Conclusion This study establishes the first chromatography-free mass spectrometry platform validated for clinical TDM of TAC. By integrating ultra-high throughput capability, minimal sample consumption, and robust analytical performance, the AEMS workflow offers a transformative analytical solution for high-demand clinical environments, including transplant centers and pediatric monitoring settings.
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高影响因子
JOURNAL OF CHROMATOGRAPHIC SCIENCE
·
2025
·Vol. 63
·期 10
·
IF 1.3
Zheng Jun-tao,Kong Jia-he,Yang Ting,Wang Xue-ding,Guan Shao-xing,Guan Yan-ping,Huang Min,Gao Xiang,Chao Kang,Zhu Xia
Deoxythioguanosine (dTG), incorporated into DNA as DNA-TG, is considered a more relevant thiopurine metabolite than erythrocyte thioguanine nucleotides, as erythrocytes are not the drug target. We established a simple and sensitive liquid chromatography–tandem mass spectrometry method to detect dTG in human blood nucleated cell DNA and validated its clinical applicability in Chinese patients with inflammatory bowel disease to improve individualized thiopurine treatment. dTG was released from 1 μg DNA in a single hydrolysis step, separated by the X-Terra RP18 column and quantified by tandem mass spectrometry with 2′- Deoxyguanosine-13C,15N2 as the internal standard. The calibration curve covered eight concentration levels (0.125–25 ng/mL) with the correlation coefficients r2 ≥ 0.99. The intra- and inter-assay variability was achieved less than 9.9%. This method was employed in a study where a total of 125 inflammatory bowel disease patients with a median DNA-TG level of 279.7 fmol/μg DNA (interquartile range 183.5 ~ 410.6 fmol/μg DNA). Nucleoside diphosphate-linked moiety X-type motif 15 variant carriers (*2, *3, *5, *6) showed significantly higher DNA-TG/dose and DNA-TG/erythrocyte thioguanine nucleotides ratios than wild-type patients (P = 0.0023, P = 0.0001). In summary, this method was simple and stable to detect dTG in DNA, which may act as a promising biomarker predicting the toxicity and efficacy in patients treated with thiopurine.
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高影响因子
MICROCHEMICAL JOURNAL
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2025
·
IF 5.1
Lingcan Kong,Haixin Chen,Qiaoyan Liu
Excessive intake bioamines is harmful to human health, and thus the development of simple, rapid and efficient detection method of bioamines in food is urgent. Herein, an unprecedented method based on a commercial molecular sieve has been developed for the determination of four bioamines (cadaverine, tyramine, histamine and tryptamine) in fruit wines by dispersive solid phase microextraction (D-μSPE) coupled to liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS). The extraction process of ultra-stable Y-type molecular sieve (USY) on bioamines belongs to physisorption, and the adsorption pattern is found in good accord with the Langmuir isotherm model. Theoretical and experimental analyses are further used to explore their binding energies, binding constants, and the maximum adsorption capacity. It is found that the adsorption is driven mainly by hydrogen bonds between USY and bioamines and water molecules. Moreover, the extraction efficiency is dependent on the binding constants and the maximum adsorption capacity of USY. The optimization of adsorption-desorption process involves the USY amount, extraction time, desorption solvent, desorption time, desorption number and cyclic usage number of USY. Under the optimum conditions, the limits of detection and quantification were found in the range of 0.2–2.5 μg L −1 and 0.6–8 μg L −1 with intra-day and inter-day precision and recoveries in a fruit wine in the range of 1.3 %–7.9 % and 91 %–104 %, respectively. Owing to the efficient enrichment and edulcoration functions of USY, the method shows negligible matrix effect and is simple, rapid, and has the potential to apply in routine work.
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高影响因子
CLINICAL BIOCHEMISTRY
·
2025
·
IF 2.1
Chunyan Zhang,Nan Bai,Yanling Yang,Yuxuan Cheng,Xiyu He,Meng Wang,Honghui Zhou,Yaping Tian
Objectives Metabolic disorders in newborns can cause significant morbidity and mortality if not diagnosed and managed early. In this study, we developed and validated a reliable LC-MS/MS method to simultaneously quantify methylmalonic acid, methylcitric acid, malonic acid, ethylmalonic acid, and total homocysteine associated with metabolic disorders. Design and methods According to Clinical Laboratory Standards Institute (CLSI) guidelines, various analytical performances (i.e., precision, linearity, accuracy and reference intervals) were rigorously evaluated. Meanwhile, sample preparation, chromatographic separation and mass spectrometric detection and incorporating stable isotope-labeled internal standards were optimized. Furthermore, calibrators and quality controls were developed to ensure standardization and traceability. Results The coefficient of variations for precision were less than 10.0 %. Meanwhile, the results showed high accuracy (recoveries: 94.57 %–109.60 %) and robust linearity (R 2 > 0.9935) over clinically relevant ranges. The limits of detection and limits of quantification for all analytes were established, enabling sensitive detection of pathological elevations. Reference intervals for pediatric populations (ages 0–1 month and 2 months to 18 years) were determined, providing essential baselines for clinical interpretation. Conclusions The newly developed method demonstrated good analytical performance and offers a standardized, high-throughput solution for clinical laboratories to improve early diagnosis and personalized management of metabolic diseases.
研究领域:
临床化学
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代谢组学
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新生儿筛查
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质谱分析
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生物医学检验
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PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2024
·
IF 2.8
Ninghong Li,Lu Liu,Dong Liu,Hengyi Yu,Guangjie Yang,Lihui Qiu,Yufei Chen,Dong Xiang,Xuepeng Gong
Tyrosine kinase inhibitors (TKIs) and triazole antifungals are the first-line drugs for treating chronic myeloid leukemia (CML) and fungal infections, respectively, but both suffer from large exposure differences and narrow therapeutic windows. Moreover, these two types of drugs are commonly used together in CML patients with fungal infections. Multiple studies and guidelines have suggested the importance of therapeutic drug monitoring (TDM) of TKIs and triazoles. Currently, methods for the simultaneous determination of both types of drugs are limited. We developed a simple, rapid, and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of three commonly used TKIs (imatinib, dasatinib, and nilotinib) and three commonly used triazoles (voriconazole, itraconazole, and posaconazole) in human plasma. The analytes were eluted on a Welch XB-C 18 analytical column (50 × 2.1 mm, 5 µm) at 0.7 mL/min, using a gradient elution of 10 mM ammonium formate (A) and methanol–acetonitrile-isopropanol (80:10:10, v / v / v ) containing 0.2 % formic acid (B) with a total analysis time of 3.5 min. The calibration curves were linear over the range from 20 to 4000 ng/mL for imatinib and nilotinib, from 2 to 400 ng/mL for dasatinib, and from 50 to 10,000 ng/mL for voriconazole, itraconazole, and posaconazole. Selectivity, accuracy, precision, recovery, matrix effect, and stability all met the validation requirements. The method was successfully used for TDM in CML patients who co-treated with both TKIs and triazoles. Drug-drug interaction analysis between TKIs and triazoles showed that a significant positive correlation was observed between imatinib and voriconazole, as well as dasatinib and voriconazole. Therefore, this method can be well applied in clinical TDM for patients receiving TKIs, triazoles, or both simultaneously.
研究领域:
临床药理学
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分析化学
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血液病学
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感染病学
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PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Xianjing Li,Minlu Cheng,Yiya Wang,Chang Shu,Bingjie Zou,Qinxin Song,Li Ding
Recently, peptide-drug conjugate (PDC) has become the most promising conjugated drug for tumor therapy after antibody-drug conjugate due to stronger tumor penetration capacity and lower immunogenicity . CBP-1018 was a PDC with dual-ligand conjugated to MMAE via a cleavable linker (MC-Val-Cit-PABC) that can be lysed by cathepsins B. In this study, two specific LC-MS/MS methods were developed and validated for the determination of CBP-1018 and its metabolite MMAE in human plasma. To prevent the cleavable MC-Val-Cit-PABC linker from degradation, a protease inhibitor (cOmplete solution) was added to the pre-cooled vacuum tubes and the separated plasma samples. The assays involved the pretreatment of CBP-1018 by protein precipitation with H 2 O-ACN (1:9, v / v ) and the extraction of MMAE by liquid-liquid extraction with ethyl acetate under alkaline condition to eliminate the interference of CBP-1018 on MMAE. The two analytes showed good linearities over the calibration ranges (R 2 ≥ 9980). Both accuracy and precision met the acceptance criteria. The validated methods were successfully applied to the phase I dose-escalation study of CBP-1018 injection in Chinese patients with solid tumors to evaluate the pharmacokinetic properties of CBP-1018 and MMAE. The results showed that CBP-1018 was eliminated immediately after injection and MMAE reached the maximum exposure at approximately 2 h after infusion. The maximum concentration of MMAE did not exceed 20.0 ng/mL, suggesting that the off-target toxicity of CBP-1018 injection was controllable.
研究领域:
药理学
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肿瘤学
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分析化学
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PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2017
·Vol. 32
·期 4
·e4156
·
IF 1.613
Qing Tong,Jia Song,Guangjie Yang,Li Fan,Wei Xiong,Jianguo Fang
Reliable methods for the determination of tryptophan and its metabolites are vital to the monitoring of biochemical states during the initiation and progression of cardiovascular disease. In the present study, a single-run liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of tryptophan (Trp) and its metabolites, including kynurenine (Kyn), kynurenic acid (KA), xanthurenic acid (XA) and 5-hydroxytryptamine (5-HT), in human plasma. The plasma samples were prepared using a protein precipitation approach, and the chromatographic separation was performed by gradient elution on a C 18 column within a total analysis time of 3.5 min. The calibration ranges were 40–20,000 ng/mL for Trp, 4–2000 ng/mL for Kyn, 0.2–100 ng/mL for KA, 0.4–200 ng/mL for XA and 1–500 ng/mL for 5-HT, and the precision and accuracy were acceptable. The evaluation of recovery and internal standard-normalized matrix effect proved that the sample preparation approach was effective and the matrix effect could be negligible. The newly developed method was successfully applied to the analysis of plasma samples from healthy individuals and myocardial infarction patients. The findings suggested that the plasma concentrations of Trp, Kyn, 5-HT as well as the concentration ratios of Kyn/Trp and Trp/5-HT might serve as biomarkers for the monitoring of acute myocardial infarction.
研究领域:
临床化学
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心血管疾病
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分析化学
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DOI
高影响因子
Analytical Methods
·
2017
·Vol. 9
·期 36
·5281-5292
·
IF 1.9
Sheng-Dong Pan,Mei-Jun Ye,Guo-Sheng Gao,Qian He,Li Wang,Xiao-Hong Chen,Qiao-Li Qiu,Mi-Cong Jin
In this paper, a monodisperse, well-defined core–shell magnetic molecularly-imprinted polymer (MD-CS-MMIP) was controllably synthesized via modified precipitation polymerization and used as a magnetic solid-phase extraction adsorbent for the simultaneous determination of six trace mycotoxins in rice samples. The as-prepared MD-CS-MMIP was fully characterized by SEM, TEM, XRD, and TG-DTG. This study is particularly concerned with the influence of the amount of oleic acid used for MD-CS-MMIP synthesis on the material morphology, components, and adsorption efficiency. The results reveal that the modification of oleic acid on the Fe3O4 surface could improve the monodispersion of core–shell MD-CS-MMIP. Moreover, MD-CS-MMIP was used as a magnetic solid-phase extraction adsorbent for the determination of six mycotoxin residues in rice samples, and the adsorption and desorption conditions of MD-CS-MMIP toward mycotoxins were optimized to obtain the highest adsorption capacity, selectivity, and desorption efficiency. Under optimal conditions, the limits of quantitation (LOQs) of the developed method toward the six mycotoxins range from 0.003 μg kg−1 to 0.01 μg kg−1. The developed method was successfully used for the determination of mycotoxins in rice samples, with recoveries in the range of 86.3 to 103.1%.
研究领域:
食品安全
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分析化学
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PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Wanqian Peng,Zhiqiang Li,Dingji Cai,Xiaocui Yi,Ji Yue (Jeff) Zhang,Guoyue Zhong,Hui Ouyang,Yulin Feng,Shilin Yang
Background Pinnatifolone A is a typical sesquiterpenoid and the primary active ingredient of Syringa oblata Lindl., has potent anti-inflammatory activity. However, Pinnatifolone A pharmacokinetic and metabolites analysis investigations in male and female rats, as well as its in vitro stability in male and female rat liver microsomes , have not been evaluated and compared. Purpose To investigate preclinical pharmacokinetic and metabolite in both genders, confirm gender differences, and provide usable information for the development of clinical applications. Methods A quick, precise, and sensitive LC-MS/MS method was created and effectively used to determine the pharmacokinetics of oral (140 mg/kg) and intravenous (6.3 mg/kg) Pinnatifolone A in male and female rats, in vitro Pinnatifolone A elimination studies in male and female rat liver microsomes. Following that, a UHPLC-Q-TOF-MS/MS technique was established to identify the metabolic profiles of Pinnatifolone A obtained from rat plasma and excreta. Results In the current study, we established for the first time an LC-MS/MS method for the quantitation of Pinnatifolone A with acceptable linearity and selectivity, recovery and matrix effect, accuracy and precision. The absolute oral bioavailability of Pinnatifolone A was approximately 30.36% in female rats, the clearance (CL) was 20.99±3.33 l/h/kg in female rats and 472.37±437.31 l/h/kg in male rats. This difference in rat genders may pertain to the sex-specific expression of hepatic enzymes as demonstrated in the metabolic stability evaluation in the present research; the male rats exhibited higher CL int(mic) (158.83±9.57 μl/min/mg protein) than female rats (76.47±7.90 μl/min/mg protein) liver microsomes, indicating higher Pinnatifolone A clearance in male rats. Twenty-four metabolites were detected and identified in female and male rats; N-acetylcysteine conjugation metabolite was the most abundant metabolites in both rat feces and urine. Furthermore, male and female rats had significantly different levels of the N-acetylcysteine conjugation metabolite. Hydrogenation metabolite was particular to female rats both in rat fecal and urine. Glucuronide conjugation metabolite was the predominant metabolite in rat plasma, and its amount in female rats was double that of male rats. Conclusions The present research is the first to report the preclinical pharmacokinetics and metabolites of Pinnatifolone A in male and female rats, confirming the gender-based differences. The findings provide a comprehensive overview for further understanding of the pharmacokinetic and metabolic characteristics of Pinnatifolone A and serve as a guide for its future development and utilization.
研究领域:
药理学
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分析化学
·
生物化学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）