COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
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2024
·
IF 1.6
Yuanxia Yang,Miaoting Yang,Lijuan Wang,Liufang He,Tao Shi
Background: The establishment and validation of methods for testing biological samples are crucial steps in pharmacokinetic studies. Currently, several methodological reports have been published on the detection of rapamycin plasma concentrations. Objective: The objective of this study was to explore an effective method for detecting rapamycin in rat whole blood biological samples. Method: In this study, we designed a rapid, sensitive, and specific liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) methodology for detecting rapamycin in rat whole blood biological samples. We comprehensively validated the specificity, linear range, lower limit of quantification (LLOQ), precision, accuracy, recovery, and stability of this method. Results: The findings of this study confirmed the successful implementation of LC-MS/MS for the detection of rapamycin, demonstrating its sensitivity, specificity, and reliability in quantitative analysis. This method ensures the accuracy and reliability of subsequent study data through our validated LC-MS/MS approach. Conclusion: The results demonstrated the successful implementation of an LC-MS/MS method for sensitive, specific, and reliable quantitative analysis of rapamycin in rat whole blood samples. This method ensures the accuracy and reliability of subsequent study data. Significance: The importance of this study lies in the successful establishment of a rapid, sensitive, and specific LC-MS/MS method for detecting rapamycin concentration in rat whole blood, ensuring the accuracy and reliability of subsequent research data. This provides a crucial tool and foundation for further understanding the metabolism and pharmacological effects of rapamycin in vivo, aiding in the advancement of drug research and clinical applications in related fields.
研究领域:
药代动力学
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药物分析
·
生物样本检测
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DOI
PubMed
高影响因子
Bioanalysis
·
2025
·
IF 1.8
Xu Yan,Shuang Wang,Ying Li,Li Cui,Zhitu Zhu,Haiwen Liu,Lu Wang,Yanru Zhu,Furong Zhao,Ping Yang
Aims Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) are indispensable for human health. Notably, imbalanced levels of maternal PUFAs during pregnancy can exert lasting impacts on the developing fetus. There is an urgent need for a robust and rapid method that can simultaneously quantify multiple n-3 and n-6 PUFAs in plasma and adapt to large-scale clinical screening.Methods Sample preparative process consisted of non-derivatized alkali hydrolyzing and liquid–liquid extraction followed by reconstituting after being blown dry with nitrogen, and the total chromatographic run time was only 5.6 min.Results The LC-MS/MS method was validated according to current national and international guidelines. Acceptable reproducibility and accuracy were shown based on the intra-day precision was 1.79%–7.02%, the inter-day precision was 0.01%–5.63%, and the accuracy was 87.42%–102.78%. The correlation coefficients of linearity were >0.9930. All measured plasma individual PUFAs levels in pregnant women significantly increased, apart from eicosapentaenoic acid (EPA, C20:5n3) and n-6/n-3 PUFA ratio levels decreased were observed. The analysis performance is satisfactory and suitable for clinical routine detection.Conclusion This method could be a valuable tool for 10 kinds of n-3 and n-6 PUFAs nutritional assessment, supplementary guidance, and intervention during pregnancy.
研究领域:
临床医学
·
营养学
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DOI
PubMed
高影响因子
Bioanalysis
·
2022
·Vol. 14
·期 7
·
IF 2.695
Xueyuan Zhang,Yuhuan Ji,Jinzhi Liu,Ji Liu,Chunlei Li,Laixin Wang,Min Meng,Limei Zhao
Background: Because of the delicate nature of liposomes, bioanalysis of free and liposomal-encapsulated drugs is among the most challenging assays to perform. Current regulatory guidance for bioanalysis is not sufficient to address the complexity of this particular formulation. Method & results: Three individual LC–MS/MS methods to quantify free amphotericin B (10–3000 ng/ml) and encapsulated amphotericin B (100–50,000 ng/ml) in pretreated human plasma and total amphotericin B (100–50,000 ng/ml) in human plasma were fully validated and applied to a bioequivalence study. The acceptance criteria and experimental design of additional validation tests using cross quality control were carefully deliberated a priori and included in the sample analysis as well. Discussion: Additional validation tests are necessary to demonstrate that the measured concentration of the intended component is accurate and free of interference from other coexisting components in the sample. These practices can be used as guidance for future liposomal drug method validation.
研究领域:
药理学
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分析化学
·
临床医学
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产品关联
DOI
PubMed
高影响因子
CHROMATOGRAPHIA
·
2022
·Vol. 85
·期 3
·221-231
·
IF 2.213
Sun Zhiping,He Lingli,Yang Qingqing,Zhang Haizhi,Xu Weiren,Qin Xinguang,Liu Gang,Hu Zhongze,Zhang Luyong,Liu Changxiao
The influence of genetic polymorphism of metabolic enzymes on drug–drug interactions (DDI) should be thoroughly investigated owing to its remarkable effect on therapeutic treatments that are futile. Here, different from earlier articles focused on various CYP subfamilies and their isoforms, the effect of genetic polymorphs of a particular isoform, CYP2C9, was comprehensively studied. Using diclofenac as probe substrate, the influence of three CYP2C9 variants (CYP2C9*1, *2 and *3) on DDI was conducted from the measurement of inhibitory ability of six drugs towards three variants. A modified LC–MS/MS method according to former report was constructed for the determination of 4ʹ-hydroxydiclofenac in CYP2C9 enzyme incubation system and validated for accuracy, precision, linearity range within the acceptance criteria for regulatory guidelines. After selecting appropriate incubation time and enzyme concentration, the kinetic parameters of three CYP2C9 variants towards diclofenac were examined and half inhibitory concentrations (IC 50 ) of six drugs towards three CYP2C9 variants were determined. IC 50 of paroxetine and losartan towards CYP2C9*2 were almost threefold higher and 2.5-fold lower than that towards CYP2C9*1, respectively. IC 50 of glibenclamide towards CYP2C9*3 was twofold more than that towards CYP2C9*1. Our results could offer effective guidelines for co-administration of these six drugs with various CYP2C9 substrates in individuals carrying variant CYP2C9 alleles, also broaden the application area of LC–MS/MS.
研究领域:
药理学
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临床医学
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分子生物学
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产品关联
DOI
高影响因子
Current Pharmaceutical Analysis
·
2022
·Vol. 18
·期 10
·919-929
·
IF 0.743
Gao Pan,Zou Qiao-gen
Background: Perampanel (PER) is a third-generation antiepileptic drug (AED). Several methods have been developed for the quantification of perampanel in plasma. The pharmacokinetic characteristics of perampanel in healthy Chinese ubjects have not been comprehensively reported.
Objective: A simple, fast and sensitive LC-MS/MS method was established and validated for the quantification of perampanel in human plasma and its application to a bioequivalence study. Methods: Chromatographic separation was accomplished on a ZORBAX Eclipse XDB-Phenyl column (4.6 mm
× 75 mm, 3.5 μm) using a binary gradient with mobile phase (A) (water containing 5 mmol/L ammonium acetate and 0.1% formic acid and (B) acetonitrile-water (95:5, v/v) at a flow rate of 0.9 mL/min and sample preparation was by one-step protein precipitation via acetonitrile. Results:
The total run time in this study was 4.5 min and the retention time of perampanel and perampanel-d5 (internal standard) were 2.30 min and 2.32 min, respectively. The method was developed and validated over the concentration range of 2.00-500 ng/mL for perampanel, with a correlation coefficient
greater than 0.9992. The inter-day precision was 3.1%-3.8% and accuracy was 98.9%-103.5%. The intra-day precision was 2.4%-6.8% and the accuracy was 97.6%- 104.9%. The extraction recovery ranged from 99.23%-103.84% and the matrix effect was not significant. Perampanel was proved to be stable
in solution and human plasma under different tested conditions. The validated method was successfully applied to a randomized, open-label, 2- period, crossover bioequivalence study in healthy Chinese subjects, and the results indicated that bioequivalence was achieved for 2 formulations of
the 4-mg perampanel tablet under both fasting and fed conditions, and both treatments were safe and well-tolerated by all study subjects. Conclusion: The validated method was successfully applied to a bioequivalence study of perampanel in human plasma and has achieved satisfactory results.
研究领域:
药理学
·
分析化学
·
临床医学
✓ 已验证
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2013
·
IF 2.947
Guangzhao He,Huixin Qi,Meiyu Wang,Jingjing Yang,Fengjiao Wen,Weipeng Wang,Chunhua Qiao,Hongjian Zhang
Schistosomiasis is an infectious disease that has been recognized as a severe health burden for some regions of the world. While praziquantel is the drug of choice, there is an unmet medical need for novel therapies with greater efficacy and resistant profile. DW-3-15 is a novel and promising prodrug possessing both adult and juvenile schistosomes killing capability. Its proposed hydrolytic products, artesunate (ARS), dihydroartemisinin (DHA) and 10-hydroxypraziquantel (10-OHPZQ), are all active in preventing schistosomal infection in relevant disease models. To support pharmacokinetic and PK-PD studies of DW-3-15, a simple, specific and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of the three active components in rat plasma. Using a short C 18 column (2.1 mm × 50 mm, 5 μm) with linear gradient, a baseline resolution of the three analytes and corresponding internal standards was achieved with a total run time of 6 min. Mass detection was carried out by electrospray ionization in positive MRM mode with ion transitions of m / z 402.2 → m / z 267.3 for ARS, m / z 302.2 → m / z 163.1 for DHA, and m / z 329.2 → m / z 219.4 for 10-OHPZQ. The method was linear over concentration ranges of 1.0–500 ng/mL for ARS, 5.0–2500 ng/mL for DHA, and 1.0–500 ng/mL for 10-OHPZQ. The accuracy was within ±10.0% for ARS, ±6.4% for DHA, and ±13.0% for 10-OHPZQ. The within-run and between-run precision of all three analytes at four concentrations tested were less than 15%, except at the LLOQ for DHA which was between 15 and 20%. The method was successfully applied to pharmacokinetic evaluation of DW-3-15 in rats following intravenous administration.
研究领域:
药理学
·
分析化学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
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