JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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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
·
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 PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
·
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
·
植物代谢组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Dong Xiang,Tinghui Zhao,Jue Wang,Yang Cao,Qiuxia Yu,Lu Liu,Hengyi Yu,Xiping Li,Ninghong Li,Yang Yi,Xuepeng Gong
A sensitive and robust LC-MS/MS method has been developed and validated for olverembatinib quantification in human plasma and cerebrospinal fluid (CSF). The method involved liquid-liquid extraction with methyl tertiary butyl ether for plasma pretreatment and precipitation enrichment with methanol for CSF pretreatment. Separation was achieved on the C18 column with gradient elutions of 10 mM ammonium formate in water and methanol-acetonitrile (50:50,v/v). Analyte detection was conducted by electrospray ionization (ESI) in a positive ion mode using multiple reaction monitoring (MRM). The m/z transitions were 533.4→433.2 for olverembatinib and m/z 502.4→394.2 for the internal standard (IS, Imatinib-d8). Calibration curves ranged from 0.500 to 50.0 ng/mL for plasma and from 0.0100 to 1.00 ng/mL for CSF. The intra- and inter-day precision and accuracy were < 15% for both plasma and CSF with four different quality control concentrations. The relative matrix effect was < 10% in plasma and artificial CSF. This method was successfully utilized for the measurement of olverembatinib concentrations in plasma and CSF from chronic myeloid leukemia patients.
研究领域:
药理学
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分析化学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2013
·
IF 2.947
Jiapeng Leng,Qing Guan,Tuanqi Sun,Yi Wu,Yanjing Cao,Yinlong Guo
Free fatty acids (FFAs) analysis of human tissue is challenging due to the low abundance of tissue lipids and interference from the complex matrix. Based on our previously reported on 2,4-dimethoxy-6-piperazin-1-yl pyrimidine (DMPP) derivatization toward carboxy group, we have further applied DMPP derivatization method in the assay of tissue FFAs in patients with thyroid carcinoma after method optimization including sample pretreatment, and derivatization condition. d 6 -DMPP labeled mixture of FFAs standard was used as the internal standard (IS). The d 0 -DMPP labeled samples (spiked with IS) were subsequently used for lipids profiling by selective reaction monitoring (SRM) detection. The DMPP derivatization combined with SRM not only allowed trace analysis of FFAs in complex matrix due to the extremely high sensitivity, but also minimized the errors in quantitation because of the very similar property between d 0 -DMPP derivatized samples and d 6 -DMPP derivatized IS. Eighteen kinds of FFAs were detected successfully with the increased level in carcinoma tissue compared with the normal tissue, which may be the results of abnormality in the metabolism of fatty acid synthases and lipids. Application of the DMPP based FFAs derivatization is expected to provide a promising tool for the investigation of lipids in vivo , especially for the research of lipid metabolism.
研究领域:
分析化学
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肿瘤学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Jie Chen,Pei Zhang,Siyuan Qin,Bei Tan,Siqi Li,Shaoran Tang,Chuyao Liao,Ying Zhang,Zunjian Zhang,Fengguo Xu
The metabolome and lipidome are critical components in illustrating biological processes and pathological mechanisms. Generally, two or more independent methods are required to analyze the two compound panels due to their distinct chemical properties and polarity differences. Here, a novel strategy integrating stepwise solid-phase extraction (SPE) and dansyl chemical derivatization was proposed for all-in-one injection LC-MS/MS analysis of serum metabolome and lipidome. In this workflow, a stepwise elution procedure was firstly optimized to separate the metabolome and lipidome fractions using an Ostro plate. Dansyl chemical derivatization was then applied to label amine/phenol, carboxyl, and carbonyl-containing sub-metabolomes. Our results demonstrated that the dansyl labeling could significantly improve chromatographic separation, enhance the MS response, and overcome the matrix effect of co-eluting lipids . Ultimately, an all-in-one injection LC-MS/MS method measuring 256 lipids (covering 20 subclasses) and 212 metabolites (including amino acids , bile acids , fatty acids , acylcarnitines, indole derivatives, ketones and aldehydes, nucleic acid metabolism, polyamines , etc.) was established. This method was applied to investigate the metabolic changes in cisplatin-induced nephrotoxicity in rats and the results were compared with previous untargeted metabolomics . The presented strategy could predominantly improve the analytical coverage and throughput and can be of great use in discovering reliable potential biomarkers in various applications.
研究领域:
分析化学
·
生物化学
·
医学
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DOI
PubMed
高影响因子
TALANTA
·
2021
·
IF 6.057
Mengyuan Qu,Shanshan Ma,Yanjie Huang,Hang Yuan,Shusheng Zhang,Gangfeng Ouyang,Yufen Zhao
Investigation into monosaccharides is critical for studies of oligosaccharides structure and function in biological processes. However, monosaccharides quantification is still challenge due to their isomeric structure and high hydrophilic properties . Besides, it was difficult to obtain isotopic internal standards (IS) of each monosaccharide in complex matrixes. Herein, we developed a novel strategy for the qualification and quantification of monosaccharides in urine using two structure analogs 1-(4-methylphenyl)-3-methyl-5-pyrazolone (MPMP) and1-phenyl-3-methyl-5-pyrazolone (PMP) as non-isotopically paired labeling (NIPL) reagents by liquid chromatograph-tandem mass spectrometry (LC-MS/MS). The derivatized monosaccharides by NIPL method not only had sufficient retention time differences on reversed-phase column, but also exhibited predominant product ion pairs ( m/z 189 & m/z 175) in the multiple reaction monitoring (MRM) mode. In this method, PMP labeled standards were adopted as one-to-one internal standards (ISs). 12 urinary monosaccharides were successfully determined and the linear ranges expanded five orders of magnitude with limit of quantification (LOQ) varied from 0.09 ng mL −1 to 0.36 ng mL −1 as well as the accuracy higher than 98.15% and the relative standard derivation (RSD) lower than 7.92%. With assistance of multivariate analysis, the targeted monosaccharide biomarkers were firstly obtained for the diagnosis of bladder cancer. By the inexpensive NIPL reagents—MPMP/PMP, the developed strategy possessed the specific advantages of low cost, simple operation, high sensitivity and high accuracy for the qualification and quantitation of monosaccharides. As expected, this method will provide an alternative application potential for targeted metabolomics analysis.
研究领域:
分析化学
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代谢组学
·
医学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6067
·
IF 1.7
Jiale Liu,Rongfei Yuan,Qi Wang,Hai Qiao,Yuling Yang,Siyu Yang,Hua Zhang,Chang Chen
High-intensity focused ultrasound (HIFU) is a noninvasive soft tissue ablation technique, which utilizes ultrasound energy to induce thermal coagulation necrosis in targeted tissues. Whether this high energy causes side effects in vivo, such as the formation of peptide bonds, has not been fully investigated. Glycylglycine is the simplest dipeptide and hence is often used as a model compound for peptide studies. In this study, we developed and validated a sensitive quantification method based on ion-exchange solid-phase extraction, liquid chromatography, and tandem mass spectrometry (SPE-LC-MS/MS) for the analysis of glycylglycine without derivatization, and then used it to evaluate whether HIFU promoted peptide bond formation in aqueous solution (without enzymes) and plasma (with enzymes). The results showed that strong cation exchange SPE significantly reduced the matrix effect and improved the sensitivity of the LC-MS/MS method. No formation of glycylglycine in the aqueous solution or plasma was observed following HIFU irradiation.
研究领域:
生物化学
·
医学工程
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Lei Ye,Xuezhen Yang,Zhenzhu Huang,Bo Zhang,Qing Tian,Yu Huang,Wei Tan,Mingjun Feng,Xiaolin Li,Hongbin Xu
Driven by the need for sustainable agriculture, using Lycium barbarum (goji) sawdust as a substrate for mushroom cultivation increases productivity while reducing environmental impact. This study evaluates the effects of different proportions of goji sawdust on the growth, yield, and metabolic profiles of pink A. cornea . Six substrate formulations were tested, with 16 % goji sawdust supporting optimal yield and quality. LC-MS/MS-based metabolomics identified 1335 metabolites, mainly organic acids and derivatives, lipids and lipid-like molecules, organoheterocyclic compounds, and benzenoids. Biomarker analysis revealed twenty to thirty-five metabolites associated with substrate variations. KEGG enrichment highlighted key metabolic pathways, including ABC transporters, amino acid biosynthesis, D-amino acid metabolism, and aminoacyl-tRNA biosynthesis, contributing to substrate adaptation. While this study offers insights into the metabolic responses of pink A. cornea to goji sawdust, future research should incorporate absolute biomarkers quantification to further validate these results and optimize substrate compositions.
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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）