Journal of pharmaceutical and biomedical analysis最新文献_第2页

Glutathione peroxidase-like activity of natural and semisynthetic phenylpropanoids and cannabinoids: An analytical investigation by a GC-MS- and HPLC-DAD-based Iwaoka’s assay 天然和半合成苯丙素和大麻素的谷胱甘肽过氧化物酶样活性：基于GC-MS和hplc - dd的Iwaoka测定法的分析研究

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-27 DOI: 10.1016/j.jpba.2026.117381

Chiara Collevecchio, Serena Fiorito, Francesco Epifano, Salvatore Genovese

The present study explores the glutathione peroxidase (GPx)-like mimicking activity of selected natural phenylpropanoids, their oxyprenylated derivatives, and natural and semisynthetic cannabinoids using a revised version of Iwaoka’s assay based on the application of GC-MS and HPLC-DAD. Thus, naturally occurring phenylpropanoids, including ferulic acid, p-coumaric acid, and umbelliferone, together with their oxyprenylated derivatives, were synthesized and tested for catalytic effects on 1,4-dithiotrhreitol (DTT^red) oxidation. While ferulic acid and p-coumaric acid displayed an appreciable GPx-like activity, their oxyprenylated counterparts exhibited a reduction in catalytic efficiency, suggesting that the carboxylic acid and free phenolic hydroxyl groups play a key role in the observed activity. Coumarin derivatives showed minimal activity, likely due to their rigid ring system. Among cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) enhanced DTT oxidation, with CBG displaying a nearly comparable effect to the reference catalyst Ebselen®. Structure–activity relationship analysis of semisynthetic CBG ethers and esters revealed that substitution patterns strongly influence catalytic performance, with diethyl and di-n-propyl derivatives demonstrating the highest GPx-like behavior. Overall, this work identifies cinnamic acids, CBG, and some of their etherified analogues as promising GPx mimetics and provides mechanistic insight into the redox properties of phenylpropanoids and cannabinoids, which may support future antioxidant drug design.

本研究基于GC-MS和HPLC-DAD的应用，利用Iwaoka的检测方法的修订版，探讨了选择的天然苯丙素、其氧丙烯化衍生物以及天然和半合成大麻素的谷胱甘肽过氧化物酶（GPx）样模拟活性。因此，合成了天然存在的苯丙酸，包括阿威酸、对香豆酸和伞花酮，以及它们的氧丙烯基化衍生物，并测试了对1,4-二硫代三甲醇（DTTred）氧化的催化作用。阿魏酸和对香豆酸表现出明显的gpx样活性，而它们的氧戊基化对应物表现出催化效率的降低，这表明羧酸和游离酚羟基在观察到的活性中起关键作用。香豆素衍生物表现出最小的活性，可能是由于它们的刚性环系统。在大麻素中，大麻二酚（CBD）和大麻二酚（CBG）增强了DTT氧化，CBG表现出与参考催化剂Ebselen®几乎相当的效果。半合成CBG醚和酯的构效关系分析表明，取代模式强烈影响催化性能，二乙基和二正丙基衍生物表现出最高的gpx样行为。总的来说，这项工作确定了肉桂酸、CBG和它们的一些醚化类似物是有前途的GPx模拟物，并为苯丙素和大麻素的氧化还原特性提供了机制上的见解，这可能支持未来抗氧化药物的设计。

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引用次数: 0

The discovery of pharmacodynamic material basis and mechanism of Shuganning injection in treating damp-heat jaundice syndrome: Combining metabolomics and serum pharmacochemistry 舒肝宁注射液治疗湿热黄疸证的药效学、物质基础及作用机制的发现：代谢组学与血清药物化学的结合

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-26 DOI: 10.1016/j.jpba.2026.117380

Yanmei He , Xiao Lin , Wanwan Zhong , Xingyan Liu , Xiuyan Yang , Youlian Yao , Meimei Li , Jianyong Zhang

Shuganning injection (SGNI) is derived from Yinchenhao decoction and has the functions of promoting diuresis, reducing jaundice and protecting the liver. It is primarily utilized in the treatment of liver diseases, particularly damp-heat jaundice. However, the pharmacodynamic material basis and specific mechanisms remain unclear. Therefore, this study aims to elucidate the pharmacodynamic material basis and mechanism of SGNI in the treatment of damp-heat jaundice syndrome (DHJS). High-throughput metabolomics was employed to identify biomarkers associated with DHJS. The migratory prototype components and metabolites present in the blood of SGNI were characterized through serum pharmacochemistry. Correlation analysis was conducted to associate the biomarkers of DHJS with the migrating components in the blood of SGNI, clarifying the pharmacodynamic basis of SGNI in treating DHJS. Furthermore, metabolic pathway enrichment analysis was performed to explore the endogenous core metabolites and key metabolic pathways, providing insights into the mechanism of SGNI in treating DHJS from the metabolic perspective. Finally, a total of 25 metabolites were identified as biomarkers for DHJS, along with 24 prototype migratory components and 38 migratory metabolites of SGNI. It was established that the pharmacodynamic substance basis of SGNI in the treatment of DHJS comprises 15 components. These components primarily exert their effects through key metabolic pathways, including pentose and glucuronate interconversions, arachidonic acid metabolism, and primary bile acid biosynthesis. In conclusion, SGNI demonstrates a significant therapeutic effect on DHJS. It has preliminarily elucidated the pharmacodynamic substance basis and mechanism of action at the metabolic level, offering a scientific foundation for the clinical application and further development of SGNI.

舒肝宁注射液（SGNI）是由银陈好汤衍生而来，具有利尿、降黄疸、护肝的作用。它主要用于治疗肝脏疾病，特别是湿热黄疸。然而，其药效学、物质基础和具体机制尚不清楚。因此，本研究旨在阐明SGNI治疗湿热黄疸综合征（DHJS）的药效学、物质基础及作用机制。采用高通量代谢组学方法鉴定与DHJS相关的生物标志物。通过血清药物化学对SGNI在血液中的迁移原型成分和代谢物进行了表征。通过相关分析，将DHJS生物标志物与SGNI血液中迁移组分进行关联，明确SGNI治疗DHJS的药效学基础。通过代谢途径富集分析，探索内源性核心代谢物和关键代谢途径，从代谢角度深入了解SGNI治疗DHJS的机制。最后，共鉴定出25种代谢物作为DHJS的生物标志物，以及24种原型迁移组分和38种SGNI迁移代谢物。确定SGNI治疗DHJS的药效学物质基础由15个组分组成。这些成分主要通过关键的代谢途径发挥作用，包括戊糖和葡萄糖醛酸的相互转化、花生四烯酸代谢和初级胆汁酸的生物合成。综上所述，SGNI对DHJS有显著的治疗作用。初步阐明了代谢水平的药效学、物质基础和作用机制，为SGNI的临床应用和进一步开发提供了科学依据。

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引用次数: 0

Chemical profiling and multi-dimensional pharmacokinetic analysis of shengmaiyin oral liquid for cardiac dysfunction 生脉饮治疗心功能障碍的化学特征及多维药动学分析

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-26 DOI: 10.1016/j.jpba.2026.117378

Lifeng Zhao , Siyang Wu , Xin Yu , Zhishan Huang , Luyang Liu , Xuehao Cheng , Zheng Yuan , Yingfei Li

Shengmaiyin oral liquid (SMY), formulated with schisandra chinensis, red ginseng, and Ophiopogon japonicus, is widely used for treating cardiac dysfunction (CD). However, its functional chemical basis and pharmacological profiles remain insufficiently explored. This study employed advanced analytical strategies to characterize the bioactive components of SMY and investigate their in silico pharmacodynamics and in vivo pharmacokinetics, providing mechanistic insights into their roles in CD treatment. Using UPLC-Q-TOF-MS/MS, 132 compounds were identified in SMY, with 31 detected in the plasma of SMY-treated mice. Among these, 21 chemicals (12 lignans and 9 saponins) were identified as key bioactives against CD. Network pharmacology and molecular docking revealed their multi-target interactions and varied binding affinities with CD-related proteins. Pharmacokinetic (PK) analysis showed that 5 compounds had high plasma exposure and rapid elimination in CD model mice. All 21 chemicals exhibited significant tissue distribution following prolonged SMY administration. The globally pharmacokinetic seeking (GPS) box analysis revealed two distinct fast and slow PK patterns among the chemicals. Notably, a highly tissue-specific and time-dependent alteration of lignan and saponin clusters was observed in the hearts of CD mice within 8 h post-administration. This study highlights the GPS box as an innovative platform for multi-dimensional PK analysis. These findings advance the integration of traditional herb medicine with modern analytical methodologies, offering new perspectives for developing precision medicine approaches in ethnopharmacology.

生脉饮口服液（SMY）是由五味子、红参、麦冬配制而成，广泛用于治疗心功能障碍（CD）。然而，其功能化学基础和药理学特征仍未得到充分探讨。本研究采用先进的分析策略来表征SMY的生物活性成分，并研究其计算机药效学和体内药代动力学，为其在CD治疗中的作用提供机制见解。通过UPLC-Q-TOF-MS/MS，在SMY治疗小鼠血浆中鉴定出132种化合物，其中31种化合物在SMY治疗小鼠血浆中检测到。其中，21种化学物质（12种木脂素和9种皂苷）被鉴定为抗CD的关键生物活性物质。网络药理学和分子对接揭示了它们与CD相关蛋白的多靶点相互作用和不同的结合亲和力。药代动力学（PK）分析表明，5种化合物在CD模型小鼠体内具有高血浆暴露和快速消除的特点。所有21种化学物质在长期服用SMY后均表现出显著的组织分布。全球药代动力学寻找（GPS）盒分析显示，两种不同的化学物质的快速和缓慢的PK模式。值得注意的是，在给药后8 h内，在CD小鼠的心脏中观察到木脂素和皂苷簇的高度组织特异性和时间依赖性改变。本研究突出了GPS盒子作为多维PK分析的创新平台。这些发现促进了传统草药与现代分析方法的结合，为发展民族药理学的精准医学方法提供了新的视角。

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引用次数: 0

Elucidating the therapeutic mechanisms of Erzhi Pills against adenine-induced chronic kidney disease: A multi-omics study 二栀丸治疗腺嘌呤性慢性肾病机制的多组学研究

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-22 DOI: 10.1016/j.jpba.2026.117374

Zepeng Zhang , Yujie Dai , Dandan Xu , Lei Zhang , Xirong Lu , Tongtong Zhu

Erzhi Pill (EZP), a classic traditional Chinese medicine formula, shows promise in ameliorating chronic kidney disease (CKD), yet its comprehensive mechanisms remain elusive. This study aimed to systematically decipher the therapeutic effects and underlying molecular mechanisms of EZP against CKD by employing an integrated multi-omics approach combined with experimental validation. In an adenine-induced CKD rat model, EZP significantly alleviated renal dysfunction, pathological injury, oxidative stress, and inflammation. Integrated analysis of serum metabolomics, renal lipidomics, and renal transcriptomics revealed that the renoprotective effects of EZP were primarily associated with the modulation of arachidonic acid metabolism, PPAR signaling pathway, and sphingolipid signaling pathway. Experimental validation demonstrated that EZP exerted anti-inflammatory effects by bidirectionally regulating the arachidonic acid metabolic network—downregulating pro-inflammatory enzymes (COX-2, LOX) while upregulating the anti-inflammatory enzyme CYP2J2. Furthermore, EZP mitigated oxidative stress and lipotoxicity by activating the PPARα/CPT1A pathway and upregulating HO-1 expression. Finally, EZP suppressed renal fibrosis by inhibiting the SPHK1/S1PR1 signaling axis and reversing epithelial-mesenchymal transition (EMT). Collectively, our findings illustrate that EZP ameliorates CKD progression through multi-target mechanisms involving coordinated anti-inflammatory, antioxidant, and anti-fibrotic activities. This study not only provides a scientific basis for the clinical application of EZP but also showcases the power of integrated omics strategies in elucidating the complex mechanisms of traditional medicines.

二栀丸（EZP）是一种经典的中药方剂，对慢性肾脏疾病（CKD）有改善作用，但其综合机制尚不清楚。本研究旨在采用综合多组学方法结合实验验证，系统解读EZP对CKD的治疗作用和潜在的分子机制。在腺嘌呤诱导的CKD大鼠模型中，EZP显著减轻肾功能障碍、病理损伤、氧化应激和炎症。血清代谢组学、肾脏脂质组学和肾脏转录组学综合分析显示，EZP的肾保护作用主要与花生四烯酸代谢、PPAR信号通路和鞘脂信号通路的调节有关。实验证实，EZP通过双向调节花生四烯酸代谢网络，下调促炎酶（COX-2、LOX），上调抗炎酶CYP2J2，发挥抗炎作用。此外，EZP通过激活PPARα/CPT1A通路和上调HO-1表达来减轻氧化应激和脂肪毒性。最后，EZP通过抑制SPHK1/S1PR1信号轴和逆转上皮-间质转化（EMT）来抑制肾纤维化。总的来说，我们的研究结果表明，EZP通过多靶点机制改善CKD的进展，包括协调的抗炎、抗氧化和抗纤维化活性。本研究不仅为EZP的临床应用提供了科学依据，而且展示了整合组学策略在阐明传统药物复杂机制方面的强大作用。

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引用次数: 0

Enantioselective high-performance liquid chromatography-tandem mass spectrometry method for bioanalysis and chemical and stereochemical stability study of N-ethylpentedrone 对映选择性高效液相色谱-串联质谱法研究n -乙基戊酮的生物分析及化学和立体化学稳定性

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-22 DOI: 10.1016/j.jpba.2026.117375

Saba Jorbenadze , Tamar Khatiashvili , Giorgia Sprega , Aluda Tchelidze , Vazha Tkemaladze , Gizo Dolidze , Simona Pichini , Magi Farré , Esther Papaseit , Melani Nuñez-Montero , Giuseppe Basile , Tivadar Farkas , Francesco Paolo Busardo , Bezhan Chankvetadze

The first high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed for enantioselective analysis of psychoactive compound N-ethylpentedrone. The method also enabled a detection of phase-1 metabolites of N-ethylpentedrone. Enantiomers some of the phase-1 metabolites were also separated. Application of this method to urine and oral fluid samples from the controlled naturalistic clinical study indicated to no enantioselective metabolism and elimination of N-ethylpentedrone. With the developed method a certain chemical and stereochemical instability of N-ethylpentedrone was also shown. Therefore, the observation about non-enantioselective pharmacokinetics of N-ethylpentedrone can be apparent and caused by post-collection racemization of this compound in the studied biological matrices.

建立了高效液相色谱-串联质谱（HPLC-MS/MS）对精神活性化合物n -乙基戊二酮的对映选择性分析方法。该方法还可以检测n -乙基戊二酮的1期代谢物。对映体的一些1相代谢物也分离。将该方法应用于对照自然临床研究的尿液和口服液样本，表明n -乙基戊二酮无对映选择性代谢和消除。该方法还显示了n -乙基戊二酮具有一定的化学和立体不稳定性。因此，观察到n-乙基戊二酮的非对映选择性药代动力学可以是明显的，这是由于该化合物在所研究的生物基质中收集后的外消旋引起的。

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引用次数: 0

The mechanism of acetyl-L-carnitine on colorectal cancer and its metabolomic study 乙酰左旋肉碱对结直肠癌的作用机制及其代谢组学研究

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-21 DOI: 10.1016/j.jpba.2026.117363

Jiayu Ning , Cuixin Cai , Xingxing Fan, Cuihua Liao, Mei Shen

Colorectal cancer (CRC) is a prevalent malignancy worldwide, with increasing incidence and mortality rates. Acetyl-L-carnitine (ALC), a natural form of L-carnitine, possesses anti-inflammatory, free radical-scavenging, and mitochondrial membrane-stabilizing properties. However, its precise mechanism of action in CRC remains unclear. To articulate the mechanism of action of ALC in CRC, we investigated its biological activity in HCT116 cells and a nude mouse xenograft model. The effects of ALC on HCT116 cells using CCK-8, colony formation, migration, invasion, and cell cycle assays. And detected oxidative stress-related indexes including reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD). The inhibitory effect of ALC on colorectal tumor growth was further validated in a nude mouse xenograft model, and untargeted metabolomic analysis was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry. The results showed that ALC can inhibit the proliferation and migration of HCT116 cells, induce cell cycle arrest and apoptosis, and affect the changes of oxidative stress indexes, and exacerbating cellular oxidative stress damage. In vivo experiments demonstrated that ALC effectively suppressed colorectal tumor growth in a dose-dependent manner. Plasma metabolomic analysis identified 10 differential metabolites between the ALC group and the control group, including meisoindigo, indole-3-acetaldehyde, etc., and 4 tumor differential metabolites, including L-proline, 3,4,5-Trimethoxytoluene, etc. Pathway enrichment analysis revealed that ALC altered 6 metabolic pathways in plasma, including tryptophan metabolism and glycine, serine, and threonine metabolism, and 5 pathways in tumor tissue, including arginine and proline metabolism and the sphingolipid signaling pathway. These findings provide novel theoretical evidence for the antitumor mechanisms of ALC in CRC.

结直肠癌（CRC）是世界范围内普遍存在的恶性肿瘤，其发病率和死亡率不断上升。乙酰左旋肉碱（ALC）是左旋肉碱的一种天然形式，具有抗炎、清除自由基和稳定线粒体膜的特性。然而，其在CRC中的确切作用机制尚不清楚。为了阐明ALC在结直肠癌中的作用机制，我们研究了其在HCT116细胞和裸鼠异种移植模型中的生物活性。利用CCK-8、集落形成、迁移、侵袭和细胞周期试验研究ALC对HCT116细胞的影响。检测氧化应激相关指标，包括活性氧（ROS）、谷胱甘肽（GSH）、丙二醛（MDA）、超氧化物歧化酶（SOD）。在裸鼠异种移植瘤模型中进一步验证ALC对结直肠癌肿瘤生长的抑制作用，并采用超高效液相色谱-串联质谱法进行非靶向代谢组学分析。结果表明，ALC可抑制HCT116细胞的增殖和迁移，诱导细胞周期阻滞和凋亡，影响氧化应激指标的变化，加重细胞氧化应激损伤。体内实验表明，ALC以剂量依赖的方式有效抑制结直肠肿瘤的生长。血浆代谢组学分析发现ALC组与对照组的差异代谢物有10种，包括异靛蓝、吲哚-3-乙醛等，肿瘤差异代谢物有4种，包括l -脯氨酸、3,4,5-三甲氧基甲苯等。途径富集分析显示，ALC改变了血浆中色氨酸代谢和甘氨酸、丝氨酸、苏氨酸代谢等6条代谢途径，改变了肿瘤组织中精氨酸、脯氨酸代谢和鞘脂信号通路等5条代谢途径。这些发现为ALC在结直肠癌中的抗肿瘤机制提供了新的理论依据。

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引用次数: 0

Metabolic profiling of Gegen-Qinlian Decoction and its modified formula in gut microbiota from healthy individuals and ulcerative colitis patients with different syndromes using UHPLC-QTOF-MS/MS and an in vitro incubation model 采用UHPLC-QTOF-MS/MS及体外培养模型研究葛根芩连汤及其加减方在健康人及不同证候溃疡性结肠炎患者肠道菌群中的代谢谱

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-21 DOI: 10.1016/j.jpba.2026.117338

Zhitian Peng , Xinyi Shi , Ying Peng , Jiaqi Zhang , Chongsheng Peng , Xudong Tang , Xiaobo Li

The efficacy of Gegen-Qinlian Decoction (GQD) and its modified formula (MGQD) against ulcerative colitis (UC) with damp-heat syndrome (UC-DHS) is closely linked to gut microbiota-mediated biotransformation. Using UHPLC-QTOF-MS/MS, this study profiled GQD and MGQD in artificial gastrointestinal fluids (AGF) and after incubation with gut microbiota from healthy individuals (HI) and UC patients with spleen deficiency syndrome (UC-SDS) and UC patients with UC-DHS. A custom-built MS data analysis workflow was developed to characterize the metabolic profiles of GQD and MGQD. The profiles comprised metabolized prototype constituents, metabolites, pathways, and metabolic rates. The results showed that GQD/MGQD remained stable in AGF. The HI, UC-SDS, and UC-DHS gut microbiota metabolized 52/60, 39/43, and 35/35 GQD/MGQD prototype compounds, resulting in 25 (GQD) and 28 (MGQD) metabolites common to all groups. All three groups exhibited similar metabolic pathways, predominantly deglycosylation to produce aglycones. However, the HI group demonstrated the highest metabolic capability, followed by UC-SDS and then UC-DHS, with superior metabolic rates, lower residual compounds, and higher metabolite abundance. Notably, the addition of two herbs to MGQD did not alter the core metabolic pathways of GQD-sourced constituents but inhibited the biotransformation of certain constituents. Further analysis revealed that glycoside metabolic rates depended on structural features: flavonoid glycosides were metabolized fastest, followed by phenylethanoid glycosides and saponins; among sugar moieties, glucosides were fastest, followed by glucuronides, xylosides, arabinosides, and apiosides. This study reveals the metabolic profiles of GQD/MGQD across different gut microbiota groups (HI, UC-SDS, UC-DHS) and provides a practical analytical workflow for herb-microbiota interaction research.

葛根芩连汤（GQD）及其加减方（MGQD）治疗溃疡性结肠炎湿热证（UC- dhs）的疗效与肠道菌群介导的生物转化密切相关。本研究采用UHPLC-QTOF-MS/MS对人工胃肠液（AGF）和健康人（HI）、UC脾虚证患者（UC- sds）、UC脾虚证患者（UC- dhs）肠道菌群培养后的GQD和MGQD进行了分析。开发了定制的MS数据分析工作流来表征GQD和MGQD的代谢谱。这些资料包括代谢的原型成分、代谢物、途径和代谢率。结果表明，GQD/MGQD在AGF中保持稳定。HI， UC-SDS和UC-DHS肠道菌群代谢52/60,39/43和35/35 GQD/MGQD原型化合物，产生25 （GQD）和28 （MGQD）共同的所有组的代谢物。所有三组均表现出相似的代谢途径，主要是去糖基化以产生苷元。HI组代谢能力最高，UC-SDS次之，UC-DHS次之，代谢率高，残留化合物少，代谢物丰度高。值得注意的是，在MGQD中添加两种草药并没有改变gqd来源成分的核心代谢途径，而是抑制了某些成分的生物转化。进一步分析发现，糖苷代谢速率与结构特征有关：黄酮类苷代谢最快，其次是苯乙醇类苷和皂苷；在糖组分中，葡萄糖苷含量最快，其次是葡萄糖苷、木糖苷、阿拉伯糖苷和芹菜苷。本研究揭示了GQD/MGQD在不同肠道微生物群（HI, UC-SDS, UC-DHS）中的代谢谱，为草药-微生物群相互作用研究提供了实用的分析工作流程。

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引用次数: 0

LC-MS peptide mapping of monoclonal antibodies using the mirror proteases trypsin and Tryp-N 使用镜像蛋白酶胰蛋白酶和胰蛋白酶n的单克隆抗体的LC-MS肽定位

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-20 DOI: 10.1016/j.jpba.2026.117361

Domantas Sargautis, Bernd Thiede

Accurate characterization of the amino acid sequence and post translational modifications (PTMs) of monoclonal antibodies (mAbs) is essential for evaluating product quality. Peptide mapping through bottom-up LC/MS analysis is a key methodology for this purpose. While trypsin is commonly the first choice for mAb digestion, it typically yields high but incomplete sequence coverage. As a result, supplementary endoproteases such as Asp-N, chymotrypsin, Glu-C or Lys-C are often employed to enhance coverage. In this report, we evaluated another endoprotease, Tryp-N, which serves as an effective alternative to trypsin for mAb analysis. The sequence coverages achieved for bevacizumab, cetuximab, NISTmAb, and trastuzumab with Tryp-N were comparable to that of trypsin, and the combination of both enzymes slightly improved overall sequence coverage. Notably, both trypsin and Tryp-N generated identical peptides beside the N- and C-terminal ends. The presence of a basic amino acid at opposite ends of the peptide often resulted in complementary sequence coverage of the MS2 of the same peptide sequences. These complementary ion series can be leveraged for precise localization of PTMs, as demonstrated in detail for deamidation, and oxidation sites as well as single amino acid variants (SAVs).

准确鉴定单克隆抗体（mab）的氨基酸序列和翻译后修饰（PTMs）是评价单克隆抗体（mab）产品质量的关键。通过自下而上LC/MS分析的肽图谱是实现这一目的的关键方法。虽然胰蛋白酶通常是单抗消化的首选，但它通常产生高但不完整的序列覆盖率。因此，补充的内源性蛋白酶如Asp-N、凝乳胰蛋白酶、Glu-C或Lys-C通常被用来增强覆盖。在本报告中，我们评估了另一种内源性蛋白酶，胰蛋白酶- n，它可以作为胰蛋白酶的有效替代品进行单抗分析。贝伐单抗、西妥昔单抗、NISTmAb和曲妥珠单抗与胰蛋白酶的序列覆盖率相当，两种酶的组合略微提高了总体序列覆盖率。值得注意的是，胰蛋白酶和胰蛋白酶-N在N端和c端产生相同的肽。在肽的相反端存在碱性氨基酸通常会导致相同肽序列的MS2的互补序列覆盖。这些互补离子系列可以用于精确定位PTMs，如脱酰胺、氧化位点以及单氨基酸变体（sav）的详细演示。

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引用次数: 0

Biopharmaceutical assessment of naloxone permeation through human respiratory epithelial tissues: A chromatographic-mass spectrometric approach with cloud based aerosol dosing and delivery 纳洛酮通过人呼吸道上皮组织渗透的生物制药评估：基于云的气溶胶给药和给药的色谱-质谱方法

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-20 DOI: 10.1016/j.jpba.2026.117366

Tasmin Ara Sultana , Diaa Shakleya , Dustin G. Brown , Patrick J. Faustino , Muhammad Ashraf , Ahmed Zidan

Understanding naloxone permeation is important for optimizing nasal delivery and supporting comparative assessment of nasal drug products. In this study, a stability-indicating LC–MS/MS method was developed and validated for the simultaneous quantification of naloxone and its related impurities, naloxone N-oxide and noroxymorphone, in in vitro permeation test receptor media. The validated method was applied to characterize naloxone permeation following cloud-based aerosol dosing across a synthetic Nuclepore Track-Etched membrane and a differentiated human EpiAirway™ mucociliary tissue model under finite-dose conditions. The analytical procedure demonstrated linearity over 0.25–20.0 ng/mL in Dulbecco’s Phosphate-Buffered Saline and Krebs–Ringer Bicarbonate Buffer, with acceptable accuracy and precision. No degradation products or additional impurities were detected in permeation samples, confirming the stability-indicating capability of the method. Naloxone exhibited rapid early-time permeation across the synthetic membrane, whereas transport across the epithelial tissue model was attenuated and plateaued, reflecting physiological barrier function. Integration of cloud-based aerosol delivery with a validated LC–MS/MS platform enables mechanistic evaluation of nasal naloxone permeation and provides a supportive in vitro framework for formulation characterization and comparative assessments.

了解纳洛酮的渗透对优化鼻腔给药和支持鼻腔药物产品的比较评估是重要的。本研究建立了一种稳定性指示的LC-MS /MS方法，用于同时定量体外渗透试验受体介质中纳洛酮及其相关杂质n -氧化物纳洛酮和去甲氧吗啡酮。在有限剂量条件下，将经过验证的方法应用于基于云的气溶胶给药，通过合成核孔轨道蚀刻膜和分化的人EpiAirway™粘膜纤毛组织模型，来表征纳洛酮的渗透。在Dulbecco的磷酸盐缓冲盐水和Krebs-Ringer碳酸氢盐缓冲液中，分析方法在0.25-20.0 ng/mL范围内呈线性，具有可接受的准确度和精密度。在渗透样品中未检测到降解产物或额外的杂质，证实了该方法的稳定性指示能力。纳洛酮在合成膜上表现出快速的早期渗透，而在上皮组织模型上的转运则减弱并趋于稳定，这反映了生理屏障功能。将基于云的气溶胶给药与经过验证的LC-MS /MS平台相结合，可以对纳洛酮鼻腔渗透进行机理评估，并为制剂表征和比较评估提供一个支持性的体外框架。

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引用次数: 0

Integrated metabolomic and proteomic analysis of cardiac tissues in a murine model of Kawasaki disease 川崎病小鼠模型心脏组织的综合代谢组学和蛋白质组学分析

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis

Pub Date : 2026-01-20 DOI: 10.1016/j.jpba.2026.117364

Panpan Liu , Yiyi Shen , Mingyang Zhang , Zhiyuan Liu , Shuhui Wang , Zhiheng Liu , Nana Wang , Jiaying Zhang , Jing Li , Guanghui Qian , Chengyao Ma , Haitao Lv , Ying Liu

Kawasaki disease (KD) is an acute systemic vasculitis in children that can result in severe cardiac complications. This study utilized an integrated proteomic and metabolomic approach to explore molecular dynamics in cardiac tissue from a Candida albicans cell wall extract (CAWS)-induced KD mouse model. Echocardiography demonstrated significant left ventricular dysfunction in the CAWS group, as evidenced by reduced ejection fraction and fractional shortening, alongside histopathological signs of inflammatory cell infiltration. Multi-omics analysis revealed 206 differentially expressed metabolites (DEMs) and 155 differentially expressed proteins (DEPs) compared to PBS controls. Bioinformatics analysis highlighted substantial disturbances in glycerophospholipid metabolism, amino acid metabolism, fatty acid synthesis, and cofactor biosynthesis pathways, with concurrent upregulation of immune- and inflammation-related proteins. Integrated analysis revealed co-enrichment in cofactor biosynthesis, amino acid metabolism, and purine metabolism pathways, and a regulatory network of key molecules was established. These findings suggest that KD-induced cardiac injury involves significant metabolic reprogramming and immune-inflammatory activation, offering new insights into the pathogenesis and providing a theoretical basis for the development of biomarkers and therapeutic targets.

川崎病是一种儿童急性全身性血管炎，可导致严重的心脏并发症。本研究利用综合蛋白质组学和代谢组学方法探索白色念珠菌细胞壁提取物（CAWS）诱导的KD小鼠模型心脏组织的分子动力学。超声心动图显示CAWS组有明显的左心室功能障碍，射血分数降低和分数缩短，同时有炎症细胞浸润的组织病理学征象。多组学分析显示，与PBS对照组相比，有206种差异表达代谢物（DEMs）和155种差异表达蛋白（DEPs）。生物信息学分析强调了甘油磷脂代谢、氨基酸代谢、脂肪酸合成和辅因子生物合成途径的实质性干扰，并伴有免疫和炎症相关蛋白的上调。综合分析发现，在辅助因子生物合成、氨基酸代谢和嘌呤代谢途径中共富集，并建立了关键分子的调控网络。这些发现表明，kd诱导的心脏损伤涉及显著的代谢重编程和免疫炎症激活，为其发病机制提供了新的认识，并为开发生物标志物和治疗靶点提供了理论基础。

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引用次数: 0