Scientific Reports
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2016
·Vol. 6
·期 1
·1-12
·
IF 5.228
Chen Ang,Zhou Xiaojing,Tang Shuowen,Liu Mingyao,Wang Xin
Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a natural naphthoquinone compound isolated from roots of Plumbago zeylanica L., has drawn a lot of attention for its plenty of pharmacological properties including antidiabetes and anti-cancer. The aim of this study was to investigate the effects of plumbagin on CYP1A2, CYP2B1/6, CYP2C9/11, CYP2D1/6, CYP2E1 and CYP3A2/4 activities in human and rat liver and evaluate the potential herb-drug interactions using the cocktail approach. All CYP substrates and their metabolites were analyzed using high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). Plumbagin presented non-time-dependent inhibition of CYP activities in both human and rat liver. In humans, plumbagin was not only a mixed inhibitor of CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, but also a non-competitive inhibitor of CYP1A2, with K i values no more than 2.16 μM. In rats, the mixed inhibition of CYP1A2 and CYP2D1, and competitive inhibition for CYP2B1, CYP2C11 and CYP2E1 with K i values less than 9.93 μM were observed. In general, the relatively low K i values of plumbagin in humans would have a high potential to cause the toxicity and drug interactions involving CYP enzymes.
研究领域:
药理学
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分析化学
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毒理学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
·
IF 3.4
Huanhuan Yang,Cong Liu,Chuanhong Zhu,Yan Zheng,Juan Li,Qianyun Zhu,Hao Wang,Xiangming Fang,Quan Liu,Man Liang,Zilong Liu
Determination of antipsychotics from biological samples is meaningful in the field of clinical and forensic medicine. Compared to blood, keratinized matrices such as hair and nails have attracted increasing attention in drug analysis for wider detection window. Nevertheless, the distribution and stability of antipsychotics in keratinized matrices are not clarified yet. Therefore, we developed a LC-MS/MS based method for simultaneous determination of 10 antipsychotics from blood, hair and nails, with high recovery (78.1–107.4%, 71.3–93.5% and 75.2–90.5%), low LOD (5–10 pg/mL, 5–10 pg/mg and 5 pg/mg) and high accuracy (96.0%−101.6%, 97.5%−102.5% and 97.6–101.7%). The method was applied to sets of blood, hair, and nail samples of 54 patients who received long-term therapy, and significant correlations between drug concentrations in blood and hair was found, while the correlation between nails and other matrices varied depending on the drug. Except for olanzapine , the concentrations of antipsychotics in segmental hair samples were consistent with drug exposure. Besides, the hair and nail samples of suspects in two forensic cases were analyzed and provided supporting evidence for the suspects’ psychiatric state. Our research offered a deeper understanding of keratinized matrix as stable and retrospective bio-samples for antipsychotics detection in forensic practice.
研究领域:
临床医学
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法医学
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DOI
PubMed
高影响因子
ANALYTICAL BIOCHEMISTRY
·
2024
·
IF 2.6
Lingfang Dong,Kun Li,Shan Gao,Wenyi Wang,Yinghua Feng,Jingying Zhang,Jie Yang,Weifeng Dong,Wei Zhang
we developed an effective protein precipitation method for determination of levamlodipine in human plasma using LC–MS/MS. Sample extraction was carried out by using liquid–liquid extraction in 96-well plate format. (S)-Amlodipine-d4 was used as internal standard (IS). The chromatographic separation was achieved using Philomen Chiral MX (2) column (3 μm, 2.1 × 100 mm). Mobile phase A was comprised of Acetonitrile (ACN), Mono ethanol amine (MEA) and Iso-Propyl alcohol (IPA) (1000:1:10, v/v/v), Mobile phase B was IPA-ACN (2:1, v/v). The flow rate was 0.4 mL/min. The total run time of each sample was 4.0 min with gradient elution. LC-MS/MS spectra were generated in positive ion mode, and multiple reaction monitoring (MRM) was used to detect the following transitions: m/z 409.20 → 238.15 for levamlodipine and 415.25 → 240.20 for (S)-Amlodipine-d4 (the IS). The method was linear from 50 to 10000 pg/mL（R 2 ＝0.9988489）,and the lower limit of quantification (LLOQ) was 50 pg/mL. This method was applied to a bioequivalence study of levamlodipine.
研究领域:
药物分析
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临床药理学
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2017
·
IF 4.95
Ze-Yuan Wang,Yi Li,Wen-Qi Chang,Jia-Yi Zheng,Ping Li,Li-Fang Liu,Gui-Zhong Xin
Superoxide anion (O 2 .- ), as the first generated reactive oxygen species (ROS), has been considered to be highly deleterious to cell functions. The measurement of intracellular O 2 .- level is of great importance to uncover its roles in a variety of oxidative damage diseases. Hydroethidium (HE) fluorescence-based method is dominating intracellular O 2 .- assay by monitoring the unique product 2-OH-E + of HE/O 2 .- reaction. However, the avoid-less cross-interference of red fluorescence limited its ability to provide trustworthy information on intracellular O 2 .- formation. By the detection of 2-OH-E + , we herein developed and validated an improved LC/MS-based method for the measurement of intracellular O 2 .- . Firstly, we demonstrated the proportionality of HE/O 2 .- reaction. Secondly, ungerimine was used as internal standard to eliminate daily basis and matrix effect in the LC/MS-based detection of 2-OH-E + . Afterward, the total protein concentration was utilized for cell number normalization. Accordingly, an equation was further proposed to calculate the relative abundance (RA) of intracellular O 2 .- . Finally, the developed method has been successfully utilized to evaluate the inhibitory effects of natural compounds on O 2 .- generation, the result of which was validated by the HE-based fluorescent measurement. Compared with the fluorescent measurement, the LC/MS-based intracellular O 2 .- assay method is more sensitive, selective and accurate.
研究领域:
分析化学
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生物化学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Minlu Cheng,Xianjing Li,Ya Li,Yiya Wang,Wenjia Li,Shuai Wang,Chang Shu,Qinxin Song,Li Ding
Recently, the approval of Trop-2 targeted antibody drug conjugate (ADC) has changed the dilemma of patients with advanced triple-negative breast cancer who rely on chemotherapeutics to improve their survival. FDA018, an ADC consisting of an anti-Trop-2 antibody conjugated with a topoisomerase inhibitor SN-38 via an acid-cleavable linker, is currently being investigated in clinical trials. Based on the urgent demand to evaluate the clinical pharmacokinetics of FDA018, ligand binding assays (LBAs) for the determination of SN-38-conjugated antibody and total antibody and LC-MS/MS methods for the determination of the free SN-38, its metabolite SN-38G and total SN-38 were developed. The comparability and DAR sensitivity evaluation of the ELISA strategies for SN-38-conjugated antibody and total antibody were emphasized. The sensitivity of the LC-MS/MS method for the simultaneous determination of SN-38 and SN-38G reached 0.500 ng/mL and 0.250 ng/mL, respectively. An effective solution has been proposed for the optical instability of the cleavable linker of FDA018 during the pretreatment process of biological samples. The established bioanalytical methods were comprehensively validated and the results satisfied the acceptable criteria of ICH M10. The validated bioanalytical methods have been applied to the single-dose pharmacokinetic study of FDA018 in patients with Trop-2-positive malignant tumors successfully, and the pharmacokinetic profiles of FDA018 and its constituent components were investigated.
研究领域:
肿瘤学
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药物分析
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临床药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2021
·
IF 3.935
Ruirui Chang,Si-Tao Xu,Hao-Wen Jin,Yong-Jie Zhao,Tian-Yu Hu,Guangji Wang,Jiankun Wang,Le Zhen
ZL-01 is a novel dual-prodrug which shows promise to be an antiviral candidate for hepatitis C virus . Here we have established a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of ZL-01 and its four metabolites (M1, M7, M8, and M9) in rat plasma with special consideration of ex vivo ZL-01, M1, and M7 stability. Several factors affecting the stability were investigated. EDTA and citric acid solution (1 M) were added to plasma to maintain the stability of analytes. The protein-precipitation method was selected with acetonitrile containing sofosbuvir as internal standard (IS). Adequate separation of ZL-01 and its metabolites was achieved on XSelect HSS T3 (3.5 µm, 4.6 × 150 mm) column by a gradient-elution with a mobile phase consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.5 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 599.2→418.5 for ZL-01, m/z 529.7→398.2 for M1, m/z 330.5→182.0 for M7, m/z 260.3→112.1 for M8, m/z 261.3→113.2 for M9 and m/z 530.4→243.4 for IS. The calibration curves exhibited good linearity (r＞0.997) for all components. The lower limit of quantitation (LLOQ) was in the range of 1–2 ng/mL. The intra-day and inter-day precisions (RSD) at three different levels were both less than 10.2% and the accuracies (RE) ranged from −3.7–7.6%. The matrix effect and extraction recovery of them ranged from 84% to 110.3% and 88.3–106.3%. This LC-MS/MS method for the simultaneous quantitation of ZL-01 and its metabolites was developed successfully and applied in the pharmacokinetic studies of these in rats. Pharmacokinetic results indicated ZL-01 would be metabolized rapidly and M8 might be the main metabolites after oral absorption.
研究领域:
药物化学
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分析化学
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病毒学
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DOI
高影响因子
Bioanalysis
·
2019
·Vol. 12
·期 1
·
IF 2.321
Libin Wang,Shouchang Gai,Xiaorui Zhang,Xiaohui Xu,Nan Gou,Xingchen Wang,Nan Zhou,Tian Feng
Aim: A sensitive and reliable LC–MS/MS method has been established and validated to the quantitation of rivaroxaban (RIV) and TAK-438 in rat plasma using carbamazepine as internal standard. Results: The procedure of method validation was conducted according to the guidelines of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and TAK-438 for the first time. When RIV and TAK-438 co-administration to rats, main pharmacokinetic parameters of TAK-438 like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increase. The main pharmacokinetic parameters of RIV have no statistically significant difference (p > 0.05) when co-administered except for t1/2 (p < 0.01). Conclusion: The results indicated that drug–drug interactions occurred between RIV and TAK-438 when co-administered to rats.
研究领域:
药理学
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分析化学
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DOI
PubMed
高影响因子
Analytical Methods
·
2024
·Vol. 16
·期 23
·3720-3731
·
IF 2.7
Rongrong Cao,Songlin Xu,Zhirui Yu,Liang Xu,Zhiqiang Ge,Qianyu Huo,Guoqing Zhu,Bin Qiao
In recent years, there has been a growing interest in the thriving monoclonal antibody (mAb) industry due to the wide utilization of mAbs in clinical therapies. Robust and accurate bioanalytical methods are required to enable fast quantification of mAbs in biological matrices, especially in the context of pharmacokinetics (PKs)/pharmacodynamics (PDs) and therapeutic drug monitoring (TDM) studies. In this investigation, we presented a novel immuno-magnetic capture coupled with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method designed for the quantification of immunoglobulin G-kappa-based mAbs in biological fluids. The immunoaffinity absorbent for mAb drug purification was meticulously crafted by immobilizing protein L onto monosize, magnetic poly(glycidyl methacrylate) (m-pGMA) beads, synthesized through dispersion polymerization. The microspheres were acquired with an average size of 1.6 μm, and the optimal binding of mAbs from the aqueous mAb solution was determined to be 45.82 mg g−1. The quantification of mAbs in 10 μL serum samples was achieved through affinity purification using m-pGMA@protein L beads (employing rituximab as an internal standard (IS)), on-bead reduction, and rapid tryptic digestion. Remarkably, the entire process, taking less than 2.5 hours, held significant potential for simplifying pretreatment procedures and minimizing analytical time. Furthermore, the developed method underwent validation in accordance with the European Medicines Agency (EMA) guidelines. The assay demonstrated commendable linearity within the 2–400 μg mL−1 range for both daratumumab and pembrolizumab. Intra- and inter-assay coefficients of variation fell within the range of 0.7% to 13.4%, meeting established acceptance criteria. Other validation parameters also conformed to regulatory standards. Ultimately, the efficacy of the method was substantiated in a pharmacokinetic study following a single-dose intravenous administration to mice, underscoring its applicability and reliability in real-world scenarios.
研究领域:
生物化学
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药物分析
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临床医学
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产品关联
DOI
PubMed
高影响因子
Chemistry Central Journal
·
2014
·Vol. 8
·期 1
·1-10
·
IF 1.663
Chen Feng,Li Hai-Long,Tan Yin-Feng,Guan Wei-Wei,Li Yong-Hui,Zhang Jun-Qing
Background Yakuchinone A has a plethora of beneficial biological effects. However, the pharmacokinetic (PK) data of yakuchinone A still remain unknown so far. Furthermore, the quantification of yakuchinone A in biological samples has not been reported in the literature. Therefore, in the present study we aimed to develop a new method for the fast, efficient and accurate assessment of yakuchinone A concentration in plasma, as a means for facilitating the PK evaluation of yakuchinone A.Results A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of yakuchinone A in rat plasma. Mass spectrometric and chromatographic conditions were optimized. Plasma samples were pretreated by protein precipitation with methanol. LC separation was performed on a Phenomenex Luna C18 column with gradient elution using a mobile phase consisting of methanol–water containing 0.5 mM formic acid (HCOOH) at a flow rate of 0.28 mL/min. ESI-MS spectra were acquired in positive ion multiple reaction monitoring mode (MRM). The precursor-to-product ion pairs used for MRM of yakuchinone A and yakuchinone B were m/z 313.1 → 137.0 and 311.2 → 117.1, respectively. Low concentration of HCOOH reduced the ion suppression caused by matrix components and clearly improved the analytical sensitivity. Yakuchinone A showed good linearity over a wide concentration range (r > 0.99). The accuracy, precision, stability and linearity were found to be within the acceptable criteria. This new method was successfully applied to analyze the rat plasma concentration of parent yakuchinone A after a single oral administration of SuoQuan capsules. Low systemic exposure to parent yakuchinone A was observed.Conclusion The proposed method is sensitive and reliable. It is hoped that this new method will prove useful for the future PK studies.
研究领域:
药理学
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分析化学
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生物医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2013
·
IF 2.591
Jing Chen,Juan Zhang,Wenpeng Zhang,Zilin Chen
Sarcosine, a potential biomarker of prostate cancer, has drawn great attention in recent years. However, controversial research keeps arising about its role as a biomarker that might come from the two isomers (α-alanine and β-alanine) of sarcosine due to their same molecular weight and similar properties, which could interfere with the accurate detection of sarcosine. In this study, a simple and sensitive method was developed for the detection of sarcosine and the two isomers by LC with ion-trap MS through a novel derivatization reagent N , N ′-dicyclohexylcarbodiimide. N , N ′-Dicyclohexylcarbodiimide is usually considered as a condensation reagent, however, it was directly used as a derivatization reagent through a rearrangement side reaction in this study. The proposed method not only improved the chromatographic retention behavior of sarcosine and its two isomers, which was a benefit to their separation, but also dramatically enhanced the detection sensitivity of sarcosine, which was more favorable for real sample analysis. The factors affecting the productivity of the derivatization reaction, such as reaction time and amount of derivatization reagent, were systematically optimized. The method shows good linearity ( R 2 > 0.99), sensitivity with LODs of sarcosine as low as 1 ng/mL, and repeatability with the RSD < 6.07%. The developed method was applied to the analysis of urine.
研究领域:
分析化学
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医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
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2024
·
IF 1.3
Lingjiao Wang,Mengqiang Zhao,Jiao Li,Hongtao Xu,Yang Song,Yuanyuan Zhao,Jing Yu,Chunhua Zhou
Background Therapeutic drug monitoring for antidepressants (ADs) is vital due to the potentially serious consequences and disputes related to medical events. Therefore, we created a quick and convenient analysis way for separation and quantification of ADs. Methods To ensure quantitative stability, we divided the 16 ADs or their metabolites into 4 pools (AD1-AD4), considering the hospital frequency that the clinician prescribed, the physicochemical properties of medicines, and the calibration range of selected ADs. After precipitation with methanol, the analytes were eluted for at least 3.5 min on a BEH C 18 analytical column by different gradient elution methods. Results: The LLOQ and LOD were 1.25–10 ng/mL and 0.42–5 ng/mL, respectively. High precision (<12 %) and accuracy (87.07–111.47 %) were demonstrated by quality control samples both within and between days. All the compounds were stable at room temperature and within −80 °C. Conclusion The method is of wide clinical and laboratory interest due to simpler sample cleanup, shorter chromatographic run times, and wider calibration range compared to other methods.
研究领域:
临床医学
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分析化学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2025
·
IF 3.1
Ningxin Li,Man Zheng,Xinqin Kong,Yang Zhou,Xinrui Yang,Qingqing He,Jing Zhou,Zijia Zhang,Jinjun Hou,Wanying Wu
Gastrodiae Rhizoma (Tianma, GR), the dried tuber of Gastrodia elata Bl., is a valuable herb for medicinal and dietary applications. Current markets feature three key cultivars: G. elata f. glauca (WTM), G. elata f. elata (HTM), and their hybrid (WHTM), with significant price variations yet lacking defined chemical authentication markers. Here, we implemented a pseudotargeted LC-MS/MS metabolomics strategy employing 534 optimized MRM transitions. This strategy was coupled with multivariate analysis – unsupervised principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) – of 40 authenticated batches, to decipher cultivar-specific chemical fingerprints. The approach identified 88 statistically validated markers, with 14 pivotal discriminators—primarily 4-Hydroxybenzyl alcohol derivatives—exhibiting distinct cultivar distribution patterns. This chemical blueprint serves as a tool for authentication in quality control and supports regulatory standard establishment for GR products.
研究领域:
中药学
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分析化学
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植物代谢组学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）