TALANTA
·
2026
·
IF 6.7
Lei Ding,Ruochen Zhang,Wenchan Deng,Feifei Chen,Shuangshuang Liu,Jinsheng Lin,Cuirong Sun
Vericiguat (VER), a novel soluble guanylate cyclase agonist for heart failure, was subjected to comprehensive forced degradation studies to assess its stability and elucidate degradation pathways. The study was conducted in accordance with ICH guidelines, including alkaline, acidic, oxidative, photolytic, and thermal stress conditions. And tentatively structural identification of degradation impurities was carried out using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). The results indicated that VER was susceptible to degradation under alkaline (NaOH) and hydrogen peroxide (H 2 O 2 ) oxidative conditions, yielding nine degradation impurities (DIs 1-7, 9, 10). Among these, eight have not been previously reported, with the exception of DI-7. Moreover, under a newly introduced free-radical oxidation condition using benzoyl peroxide (BPO), two additional novel impurities (DI-8 and DI-11) were generated. And two major degradants (DI-3-2 and DI-5) were isolated and their structures were confirmed by 1Dimension/2Dimension-Nuclear Magnetic Resonance (1D/2D-NMR) analysis. Based on the structures of the degradation impurities, the degradation pathways were elucidated and the molecular stability was investigated. The results demonstrate that the primary degradation mechanisms involved pyrimidine ring cleavage, oxidation of the amino group, hydrolysis of ester and amide bonds, as well as intramolecular cyclization and rearrangement. This study successfully established a comprehensive impurity profile for VER and provided robust scientific data for formulating its quality standards, thereby supporting stability assessment and quality control during pharmaceutical development.
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JOURNAL OF MASS SPECTROMETRY
·
2026
·Vol. 61
·期 5
·e70059
·
IF 2.1
Yongjuan Jia,Xingli Liu,Yongmei Chen,Wei Li
Comprehensive profiling of sex steroid hormones (SSHs) is of great significance for elucidating the pathogenesis of SSHs-related diseases. However, it is challenging because of the low endogenous abundance and the presence of multiple analytes with similar structures and isomers. In this study, we developed a simple, rapid, and clinically transferable method for the profiling of 28 SSHs in human serum samples. After liquid–liquid extraction, the serum samples were directly detected by liquid chromatography–tandem mass spectrometry. Twenty-three isomers or structural analogues were separated on Kinetex F5 column within 14 min. Good linearities were achieved in the quantitative range for each analyte with the regression coefficients R 2 > 0.99088. The limits of quantitation of the method were in the range from 0.005 to 1 ng/mL. The recoveries were in the range of 90.4%–107.9% with the intraday and interday precisions within 14.35%. This method had been successfully applied for the determination of SSHs in human serum samples with simple operation and good accuracy and could provide a viable approach for clinical screening of SSHs.
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METHODS
·
2024
·
IF 4.2
Sisi Gong,Qingshui Wang,Jiewei Huang,Rongfu Huang,Shanshan Chen,Xiaojuan Cheng,Lei Liu,Xiaofang Dai,Yameng Zhong,Chunmei Fan,Zhijun Liao
Background Breast cancer (BC), the most common form of malignant cancer affecting women worldwide, was characterized by heterogeneous metabolic disorder and lack of effective biomarkers for diagnosis. The purpose of this study is to search for reliable metabolite biomarkers of BC as well as triple-negative breast cancer (TNBC) using serum metabolomics approach. Methods In this study, an untargeted metabolomics technique based on ultra-high performance liquid chromatography combined with mass spectrometry (UHPLC-MS) was utilized to investigate the differences in serum metabolic profile between the BC group (n = 53) and non-BC group (n = 57), as well as between TNBC patients (n = 23) and non-TNBC subjects (n = 30). The multivariate data analysis, determination of the fold change and the Mann-Whitney U test were used to screen out the differential metabolites. Additionally, machine learning methods including receiver operating curve analysis and logistic regression analysis were conducted to establish diagnostic biomarker panels. Results There were 36 metabolites found to be significantly different between BC and non-BC groups, and 12 metabolites discovered to be significantly different between TNBC and non-TNBC patients. Results also showed that four metabolites, including N-acetyl-D-tryptophan, 2-arachidonoylglycerol, pipecolic acid and oxoglutaric acid, were considered as vital biomarkers for the diagnosis of BC and non-BC with an area under the curve (AUC) of 0.995. Another two-metabolite panel of N-acetyl-D-tryptophan and 2-arachidonoylglycerol was discovered to discriminate TNBC from non-TNBC and produced an AUC of 0.965. Conclusion This study demonstrated that serum metabolomics can be used to identify BC specifically and identified promising serum metabolic markers for TNBC diagnosis.
研究领域:
肿瘤学
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代谢组学
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生物信息学
·
临床诊断
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Toxics
·
2025
·Vol. 13
·期 5
·352
·
IF 4.1
Yubing Yan,Bowen Liang,Jiawen Yang,Qing Deng,Xiaoying Liang,Hui Chen,Bibai Du,Lixi Zeng
Fluorescent brighteners (FBs) are a class of chemicals extensively used in industrial and consumer products. Their environmental occurrences and potential health risks have raised significant concerns. However, the lack of analytical methods for FBs in human samples has hindered the accurate assessment of internal exposure levels. Addressing this gap, this study developed and validated a novel method for the simultaneous determination of 13 FBs at trace levels in human plasma using solid-phase extraction combined with HPLC-MS/MS. The method employed EMR-Lipid SPE columns, which can selectively adsorb phospholipids for plasma sample pre-treatment. Detection was achieved through positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) modes. The results showed that all 13 FBs exhibited good linearity within their respective ranges, with correlation coefficients (R2) greater than 0.992. The method quantitation limits (MQLs) of the FBs ranged from 0.012 to 0.348 ng/mL, and the spiked recovery rates ranged from 61% to 98%. The method was successfully applied to analyze 10 adult plasma samples, detecting 10 FBs with total concentrations ranging from 0.221 to 0.684 ng/mL. This study provides a reliable analytical method for determining FBs in human plasma, providing a basis for further research on human internal exposure to FBs and associated health risk assessments.
研究领域:
分析化学
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环境健康学
·
毒理学
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JOURNAL OF LIPID RESEARCH
·
2020
·Vol. 61
·期 4
·580-586
·
IF 4.483
Teng-Fei Yuan (袁;腾;飞,Juan Le (乐;娟,Shao-Ting Wang (王;少;亭,Yan Li (李;艳
Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and lack the evaluation of accuracy. Here, we developed an LC/MS/MS method for the simultaneous quantification of 12 steroid hormones: testosterone, pregnenolone, progesterone, androstenedione, corticosterone, 11-deoxycortisol, cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, estriol, and estradiol. Steroids and spiked internal standards in 100 μl serum were extracted by protein precipitation and liquid-liquid extraction. The organic phase was dried by evaporation, and isonicotinoyl chloride was added for steroid derivatization, followed by evaporation under nitrogen and redissolution in 50% methanol. Chromatographic separation was performed on a reverse-phase PFP column, and analytes were detected on a triple quadrupole mass spectrometer with ESI. The lower limits of quantification ranged from 0.005 ng/ml for estradiol to 1 ng/ml for cortisol. Apparent recoveries of steroids at high, medium, and low concentrations in quality control samples were between 86.4% and 115.0%. There were limited biases (−10.7% to 10.5%) between the measured values and the authentic values, indicating that the method has excellent reliability. An analysis of the steroid metabolome in pregnant women highlighted the applicability of the method in clinical serum samples. We conclude that the LC/MS/MS method reported here enables steroid metabolome analysis with high accuracy and reduced serum consumption, indicating that it may be a useful tool in both clinical and scientific laboratory research.
研究领域:
临床医学
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分析化学
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Scientific Reports
·
2025
·Vol. 15
·期 1
·1-8
·
IF 3.9
Liu Hao,Cai Meng,Peng Yong,Miao Jing-kun,Yu Jin
While remifentanil, etomidate, and rocuronium are increasingly used for cesarean section due to their favorable hemodynamic stability and fetal safety profile, their pharmacokinetics and potential effects on neonates remain poorly understood. This study developed and validated a rapid, sensitive LC–MS/MS method for simultaneous quantification of the three anesthetics in microsamples of 10 μl serum, followed by a paired maternal and umbilical cord serum investigation. After protein precipitation with acetonitrile, analytes were separated within 4 min using positive electrospray ionization in MRM mode. Method validation demonstrated excellent linearity (R 2 > 0.99) for all compounds, with LLOQs of 0.15 ± 0.02 ng/mL (remifentanil), 16.87 ± 0.51 ng/mL (etomidate), and 106.73 ± 8.63 ng/mL (rocuronium). Precision (intra-/inter-day < 15%) and minimal carry-over (< 5%) met bioanalytical standards. Applied to 20 maternal-newborn pairs, the method quantified differential drug distribution: maternal arterial concentrations (remifentanil 4.75 ± 0.19 ng/mL; etomidate 412.71 ± 35.29 ng/mL; rocuronium 7.08 ± 0.48 μg/mL) exceeded umbilical vein levels (2.43 ± 0.13 ng/mL; 302.15 ± 29.03 ng/mL; 0.86 ± 0.16 μg/mL), which were higher than umbilical artery concentrations (1.33 ± 0.15 ng/mL; 166.24 ± 21.53 ng/mL; 0.44 ± 0.77 μg/mL). Calculated placental transfer rates significantly differed among anesthetics (remifentanil 0.52 ± 0.02; etomidate 0.75 ± 0.04; rocuronium 0.13 ± 0.02; all P < 0.001), reflecting distinct pharmacokinetic behaviors. The validated method enables reliable microvolume analysis for perinatal pharmacokinetic studies, particularly valuable when sample availability is limited. Its rapid throughput and sensitivity make it suitable for clinical research applications investigating maternal–fetal drug transfer dynamics.
研究领域:
分析化学
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药代动力学
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麻醉学
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妇产科学
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新生儿学
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临床研究
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ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Shiwen Zhou,He Tang,Lu Gao,Wangyu Li,Jiancong Liao,Xihe Yang,Yuanjiang Pan,Hongru Feng
Background Oligonucleotide-based drugs have gained significant attention as a promising class of therapeutics due to their precise ability to regulate gene expression. However, the presence of impurities in these drugs can compromise their safety, efficacy, and stability. Therefore, the identification and detailed analysis of these impurities are crucial. Traditional methods may struggle to detect subtle impurities, such as oxidation and hydrolysis products, which necessitate the development of more advanced and reliable analytical techniques for oligonucleotide therapeutics. Results In this study, we introduce a novel analytical method that combines heart-cutting two-dimensional liquid chromatography (2D-LC) with tandem mass spectrometry (MS/MS) to effectively separate, analyze, and identify impurities in oligonucleotide-based drugs. The first dimension utilizes anion exchange chromatography (AEX) to separate oligonucleotides based on their negative charge, while the second dimension employs reverse ion-pair chromatography (RIPC) for further purification and compatibility with mass spectrometry. This 2D-LC-MS/MS approach provides a sensitive and accurate means of identifying and quantifying impurities, including oxidation and hydrolysis products. The method was applied to two RNA interference (RNAi) drugs, Givosiran and Patisiran, where 3 and 20 impurities were identified, respectively. Additionally, sequencing analysis using data-dependent acquisition (DDA-MS/MS) enabled the determination of the molecular weight and structural characteristics of these impurities, offering a comprehensive and detailed view of the impurity profiles. Significance This novel heart-cutting 2D-LC-MS/MS method offers a significant advancement in the analysis of impurities in oligonucleotide-based therapeutics. It provides high sensitivity, enabling the identification of subtle impurities that are often challenging to detect. By applying this technique to RNAi drugs, we demonstrate its potential to enhance the safety, efficacy, and stability of oligonucleotide-based therapies, making it a valuable tool for the pharmaceutical industry.
研究领域:
药物分析
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分析化学
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生物治疗学
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质谱分析
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色谱分析
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药物研发
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生物药剂学
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2019
·
IF 2.813
Jian Ren,Chang-Liang Hu,Zheng-Ping Zhang,Rong Chen,Shi-Bao Yang,Zhen-Yu Miao,Lu-Ning Sun,Yong-Qing Wang
(+)-Borneol, a bicyclic monoterpene , has been shown to possess valuable biological properties and potential as a pharmaceutical agent due to anti-inflammatory, anti-oxidant and GABA receptor-enhancing functions; it also enhances the permeability of the blood brain barrier to improve the efficacy of CNS drugs. In this study, we have developed a simple, selective, and rapid liquid chromatography-tandem mass spectrometry method for the assay of (+)-borneol in rat plasma. Verapamil was used as an internal standard. Plasma samples were deproteinized using methanol. The analyte was detected by a mass spectrometer with positive atmospheric pressure chemical ionization by multiple reaction monitoring mode for transitions at m / z [M + H] + 137.2 → 81.0 for (+)-borneol and 455.2 → 165.1 for verapamil. The method has been fully validated to ensure good selectivity, a satisfactory lower limit of quantification at 10.0 ng/mL, acceptable intra- and inter-day accuracy, and high precision. The method was used for the pharmacokinetic evaluation of (+)-borneol in Sprague-Dawley rats after intravenous, oral, and sublingual administration. The results indicate that oral bioavailability of (+)-borneol was extremely low but sublingual administration yielded rapid absorption and favorable bioavailability of (+)-borneol.
研究领域:
药理学
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分析化学
·
药物代谢
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Analytical Methods
·
2015
·Vol. 7
·期 12
·4919-4926
·
IF 1.821
Jun-Qing Zhang,Yong Wang,Hai-Long Li,Qi Wen,Hang Yin,Nian-Kai Zeng,Wei-Yong Lai,Na Wei,Shou-Qian Cheng,Sheng-Li Kang,Feng Chen,You-Bin Li
The rhizomes of Alpinia officinarum Hance (Zingiberaceae family) have been used as antiemetics, stomachics and analgesics in Asia for centuries. Unfortunately, the aerial parts were thrown away as waste whilst harvesting the rhizomes of A. officinarum. Recently, scientists reported that the ethanol extract of the aerial parts displayed anti-proliferation activity through mitochondrial pathway-induced cell apoptosis. However, the chemical composition of this extract remained largely unknown. We have identified sixteen chemicals including twelve flavonoids and four diarylheptanoids from the methanol extract of A. officinarum leaves using liquid chromatography/tandem mass spectrometry (LC-MS/MS). In order to better explore the potential value of the aerial parts, we need to know what the main constituents occurring in the aerial parts are and how the content of these chemicals is influenced by growing period. In the present study, a LC-MS/MS method was developed and validated for determination of seventeen compounds occurring both in the aerial parts and rhizomes sampled at different growing periods. The validation indices evaluated were satisfactory and the method was successfully employed to analyze the above-mentioned plant samples. Notably, we found that the content of these compounds, except for quercetin, was higher in rhizomes than in aerial parts. The six major constituents both in the aerial parts and rhizomes were galangin, kaempferide, hexahydrocurcumin, pinocembrin, chrysin and isorhamnetin. Moreover, the trends of change in content along with the sample period for most of the monitored phytochemicals were almost similar between the aerial parts and rhizomes. Our study should be of value in arousing everyone's interest to make the best use of the aerial parts of A. officinarum in the future.
研究领域:
药用植物学
·
分析化学
·
植物科学
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FOOD CHEMISTRY
·
2026
·
IF 10.4
Mohan Li,Chenhao Jiang,Dian Zhou,Kewei Chen,Muying Du,Zsolt Zalán,Sameh Awad,Jianquan Kan
A multi-technique framework dissects AFB1 matrix interference in PPC. • Demonstration of a strong solvent-dependent matrix interference in AFB1 extraction. • Non-targeted metabolomics revealed solvent-specific co-extract profiles. • Acetonitrile/water (80:20) achieved >90% recovery with minimal interference. • Distinct AFB1 interaction modes underlie stage-dependent solvent efficacy. Pressed peanut cake (PPC) is a valuable plant-based protein source, but its complex matrix might lead to underestimation of aflatoxin B1 (AFB1). This study established a multi-technique diagnostic framework integrating UV–Vis, FTIR, LC–MS/MS, and SEM to systematically dissect matrix interference in different extraction solvents, ultimately correlating with AFB1 detection. It was found that, due to lipid interference, the use of nonpolar solvents during extraction not only significantly amplified detection errors but also severely compromised extraction efficiency, resulting in an analytical error exceeding 85%. Systematic profiling revealed that conventional methanol/water extraction introduced dual errors, attributable to either inefficient toxin extraction or excessive pigment co-extraction, leading to an AFB1 underestimation up to 50%. Acetonitrile/water was identified as the optimal extraction solvent, minimizing interferents and achieving consistent AFB1 recoveries >90%. This work not only provides a practically applicable detection protocol but also offers a clear mechanistic explanation for the observed errors. Download: Download high-res image (219KB) Download: Download full-size image
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Drug Design Development and Therapy
·
2026
·
IF 6.1
Huanchen Li,Hongkun Wu,Shouhong Gao,Lili Cui,Jingjie Xu,Jianguo Sun,Zhijun Liu,Zhipeng Wang,Xia Tao
Objective Atorvastatin is frequently used in combination with almonertinib in lung cancer patients who present with comorbid dyslipidemia. Both drugs are metabolized by CYP3A4, potentially leading to drug-drug interactions (DDIs) that increase the risk of adverse reactions. This study aimed to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying almonertinib and atorvastatin and evaluate the DDIs between these two drugs in rats.Methods An LC-MS/MS method was developed to determine almonertinib and atorvastatin in rat plasma and was fully validated in accordance with the ICH M10 bioanalytical method validation guideline and Chinese Pharmacopoeia 2020 Edition. Rats were divided into 5 groups (n=7 per group), and received the following treatments: almonertinib alone, atorvastatin alone, almonertinib combined with atorvastatin, vehicle control, or almonertinib after a long-term regimen of atorvastatin. The plasma samples were collected from each rat and analyzed using this method. The pharmacokinetic parameters were calculated and the DDIs were evaluated.Results An LC-MS/MS method was established and validated according to the requirements. Animal studies revealed that co-administration of almonertinib with atorvastatin significantly increased Cmax, AUC0-t, and AUC0-∞ (all p < 0.05), prolonged t1/2 (p < 0.05) and decreased CLz/F, Vz/F (both p < 0.05) of both drugs. Following a 7-day administration of atorvastatin, the DDIs between the two drugs generally weakened, but still differed significantly from those observed with single-drug administration.Conclusion The study successfully established an LC-MS/MS method for simultaneous determination of almonertinib and atorvastatin and assessed the DDIs of these two drugs in rat. Animal experiment demonstrated significant DDIs between two drugs no matter single dose or multiple doses were administered, which obviously increased the drug exposure and inhibited elimination. Close attention should be paid to the combination regimens of these two drugs in clinical practice.
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Analytical Methods
·
2021
·Vol. 13
·期 29
·3242-3248
·
IF 2.896
Pengpeng Zhang,Shuai Liu,Shuang Yang,Yuanhong Wang,Tingfu Jiang,Mingming Yu,Zhihua Lv
A simple and sensitive method for the simultaneous determination of chito-oligosaccharides (COSs) with degrees of polymerization (DPs) from 2 to 7 was developed and used for COS quantification in rat plasma. Samples were separated on a Waters XBridge Amide column (3.5 μm, 2.1 × 150 mm) by isometric elution with 10 mM aqueous ammonium acetate (pH = 9) in acetonitrile and 10 mM aqueous ammonium acetate (pH = 9) (v/v, 50 : 50) employing multiple reaction monitoring (MRM) detection. Analytes and internal standards (IS) were extracted from rat plasma by protein precipitation with acetonitrile. The assay was linear over a concentration range of 20–10 000 ng mL−1 for COS2–7. The intra-day and inter-day precision of the investigated components exhibited an RSD within 15%, and the accuracy (RE%) ranged from −7.3% to 7.6%. The extraction recoveries of the six constituents were determined to be between 82.5% and 94.3%. No significant matrix effects for COS2–7 were observed in rat plasma. COS in plasma remained stable for 24 h at room temperature (short-term), after freeze–thaw cycles, and 30 days in a −40 °C freezer. In comparison to reported COS quantitation methods, this method is simple, sensitive and cost-effective and could be used for the simultaneous quantitation of COS2–7. This method meets the Food and Drug Administration guidelines and had been successfully applied to the analysis of pharmacokinetic samples collected from rats.
研究领域:
分析化学
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药代动力学
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生物医学
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高影响因子
危险品化学品经营许可证（带存储）