Journal of Pharmaceutical and Biomedical Analysis Open最新文献_第3页

Identification and characterization of forced degradation products of lumateperone tosylate by LC-HRMS, GC-MS, NMR, and in silico toxicity prediction 利用LC-HRMS、GC-MS、NMR和硅毒性预测方法鉴定和表征甲基磺酸硫醚酮的强制降解产物

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-12-01 Epub Date: 2025-08-04 DOI: 10.1016/j.jpbao.2025.100085

Nehal Bhatt , Devendra Sonaje , Vijiaya Madhyanapu Golla , Rahul Khemchandani , Roshitha K. R , Arun Kumar Gupta , Gananadhamu Samanthula

This study presents a detailed forced degradation profiling of lumateperone under stress conditions to develop a stability-indicating method capable of separating degradation products (DP-1 to DP-11), followed by their identification and characterization using hyphenated analytical techniques. Significant degradation was observed under oxidative, acidic, alkaline, and photolytic conditions. Oxidative stress generated an intensely colored quinone derivative (DP-2) as a major degradation product along with DP-3, DP-4, and DP-6. Alkaline hydrolysis yielded N-dealkylated and hydroxylated species (DP-1, DP-4, DP-5) and also produced a volatile degradation product, DP-7. Photolytic stress resulted in DP-2 and DP-8, whereas neutral hydrolysis led to the formation of DP-1, DP-2, DP-4, and DP-7. Notably, acidic hydrolysis in hydrochloric acid triggered dimer degradation product (DP-9) and chlorinated positional isomers of lumateperone (DP-10 and DP-11). The chemical structures of DP-1 to DP-6 and DP-8 to DP-11 were proposed by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). DP-7 was identified as 1-(4-Fluorophenyl)ethanol using gas chromatography-mass spectrometry (GC–MS). The major degradation product, DP-2, was isolated and further characterized by nuclear magnetic resonance (NMR). A few DPs shared structural features with previously reported metabolites, suggesting a resemblance between chemical degradation and metabolic processes. The developed method was validated in accordance with ICH Q2(R1), demonstrating excellent linearity (r² > 0.999), accuracy, precision, specificity, and robustness. In silico toxicity analysis using ADMET Predictor® flagged four DPs (DP-1, DP-2, DP-5, and DP-6) with mutagenic alerts and predicted additional hepatotoxic, cardiotoxic, and receptor-mediated risks.These findings support formulation and quality management of lumateperone.

本研究详细介绍了应力条件下lumateperone的强制降解分析，以开发一种能够分离降解产物（DP-1至DP-11）的稳定性指示方法，然后使用连线分析技术对其进行鉴定和表征。在氧化、酸性、碱性和光解条件下观察到明显的降解。氧化应激产生了与DP-3、DP-4和DP-6一样的颜色强烈的醌衍生物（DP-2）。碱性水解产生n -脱烷基和羟基化产物（DP-1, DP-4, DP-5），并产生挥发性降解产物DP-7。光解胁迫生成DP-2和DP-8，而中性水解生成DP-1、DP-2、DP-4和DP-7。值得注意的是，盐酸中的酸性水解引发了二聚体降解产物（DP-9）和氯代位置异构体（DP-10和DP-11）。采用液相色谱-高分辨率质谱（LC-HRMS）分析了DP-1 ~ DP-6和DP-8 ~ DP-11的化学结构。采用气相色谱-质谱联用（GC-MS）鉴定DP-7为1-（4-氟苯基）乙醇。对主要降解产物DP-2进行了分离，并用核磁共振（NMR）对其进行了表征。一些DPs与先前报道的代谢物具有相同的结构特征，表明化学降解和代谢过程之间存在相似性。该方法按照ICH Q2（R1）进行验证，具有良好的线性(r²>；0.999)，准确度、精密度、特异性和稳健性。在硅毒性分析中，使用ADMET Predictor®标记四种dp （DP-1, DP-2， DP-5和DP-6）具有致突变警报，并预测额外的肝毒性，心脏毒性和受体介导的风险。这些发现为氟替他酮的配方和质量管理提供了支持。

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引用次数: 0

N-nitrosamine risk assessment in pharmaceuticals: Where are we from a regulatory point of view in 2025? 药品中n -亚硝胺风险评估：从监管的角度来看，2025年我们在哪里？

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-12-01 Epub Date: 2025-07-21 DOI: 10.1016/j.jpbao.2025.100084

Yue Zhang, Joëlle Widart, Eric Ziemons, Philippe Hubert, Cédric Hubert

N-nitrosamines have been a concern for decades due to their potential mutagenicity and widespread occurrence across various matrices. While evidence suggests carcinogenicity in animals, their potential carcinogenicity in humans has prompted their initial inclusion in the “cohort of concern” since in ICH M7(R1), and the current ICH M7(R2) guideline is now in effect. Intensified control of N-nitrosamines began in 2018 following the detection of N-nitrosodimethylamine in valsartan-containing products. Subsequent investigations revealed N-nitrosamine contamination across multiple drug classes, triggering widespread recalls, withdrawals, and regulatory actions. Recently, the emergence of N-nitrosamine drug substance-related impurities and drug linker-related impurities has drawn additional regulatory attention. This review presents the methodologies used to determine the acceptable daily intake of N-nitrosamines and traces the evolution of regulatory guidelines, offering a comparative analysis of the 3-step investigation approaches adopted by the European Medicines Agency and Food and Drug Administration. It provides a comprehensive examination of potential root causes for N-nitrosamine contamination, outlines the analytical requirements for confirmatory testing, as well as mitigation strategies to prevent or minimize contamination. Additionally, the review summarizes risk assessment tools used to predict N-nitrosamine formation. By presenting a comprehensive workflow for impurity investigations, this review aims to assist industrial stakeholders in managing N-nitrosamine risks, ensuring regulatory compliance, and safeguarding public health.

n -亚硝胺由于其潜在的诱变性和广泛存在于各种基质中，几十年来一直受到关注。虽然有证据表明它们对动物具有致癌性，但它们对人类的潜在致癌性促使它们自ICH M7（R1）以来首次被列入“关注队列”，目前的ICH M7（R2）指南现已生效。在缬沙坦产品中检测到n-亚硝基二甲胺后，2018年开始加强对n-亚硝胺的控制。随后的调查显示，n -亚硝胺污染了多种药物类别，引发了大范围的召回、下架和监管行动。最近，n -亚硝胺类原料药相关杂质和药物连接物相关杂质的出现引起了监管部门的额外关注。本综述介绍了用于确定n -亚硝胺每日可接受摄入量的方法，并追溯了监管指南的演变，对欧洲药品管理局和食品药品管理局采用的三步调查方法进行了比较分析。它全面审查了n -亚硝胺污染的潜在根本原因，概述了验证性测试的分析要求，以及防止或尽量减少污染的缓解战略。此外，综述总结了用于预测n -亚硝胺形成的风险评估工具。通过介绍杂质调查的综合工作流程，本综述旨在帮助工业利益相关者管理n -亚硝胺风险，确保法规合规性，并维护公众健康。

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引用次数: 0

Comparative analysis of MS/MS search algorithms in label-free shotgun proteomics for monitoring host-cell proteins using trapped ion mobility and ddaPASEF 利用捕获离子迁移率和ddaPASEF监测宿主细胞蛋白的无标记鸟枪蛋白组学中MS/MS搜索算法的比较分析

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-12-01 Epub Date: 2025-07-21 DOI: 10.1016/j.jpbao.2025.100082

Somar Khalil, Michel Plisnier

Host cell proteins (HCPs) are critical quality attributes that can impact the safety, efficacy, and quality of biotherapeutics. Label-free shotgun proteomics is a vital approach for HCP monitoring, yet the choice of tandem mass spectrometry (MS/MS) search algorithms directly influences identification depth and quantification reliability. In this study, six prominent MS/MS search tools (Mascot, MaxQuant, SpectroMine, FragPipe, Byos, and PEAKS) were systematically benchmarked for their performance on complex samples spiked with isotopically labeled proteins from Chinese hamster ovary cells. The data were acquired using trapped ion mobility spectrometry and parallel accumulation–serial fragmentation in data-dependent acquisition mode. Key performance metrics, including peptide and protein identifications, data extraction precision, fold-change (FC) accuracy, linearity, and measurement trueness, were evaluated. A Bayesian modeling framework with Hamiltonian Monte Carlo sampling was employed to robustly estimate FC means and variances, alongside local false discovery rates through posterior probability calibration. Bayesian decision theory, implemented via expected utility maximization, was used to balance accuracy against posterior uncertainty and provide a probabilistic assessment of each tool’s performance. Through this cumulative analysis, variability across tools was observed: Byos and SpectroMine excelled in quantitative accuracy with minimal bias, FragPipe provided high precision and quantifiability, PEAKS offered deep protein coverage, Mascot showed strong trueness, and MaxQuant exhibited moderate identification performance with greater variability at lower spike levels. This study establishes a rigorous, data-driven framework for tool benchmarking and offers guidance for selecting MS/MS tools suited to HCP monitoring in biopharmaceutical development.

宿主细胞蛋白（HCPs）是影响生物治疗药物安全性、有效性和质量的关键质量属性。无标签霰弹枪蛋白质组学是监测HCP的重要方法，但串联质谱（MS/MS）搜索算法的选择直接影响鉴定深度和定量可靠性。在这项研究中，系统地对六个著名的MS/MS搜索工具（Mascot、MaxQuant、SpectroMine、FragPipe、Byos和PEAKS）在含有中国仓鼠卵巢细胞同位素标记蛋白的复杂样品上的性能进行了基准测试。数据采用捕获离子迁移率光谱法和数据依赖获取模式的平行累积-序列破碎法获取。关键性能指标，包括肽和蛋白质鉴定，数据提取精度，折叠变化（FC）准确性，线性度和测量准确性进行了评估。采用哈密顿蒙特卡罗抽样的贝叶斯建模框架稳健地估计FC均值和方差，并通过后验概率校准局部错误发现率。贝叶斯决策理论通过期望效用最大化实现，用于平衡准确性和后验不确定性，并提供每种工具性能的概率评估。通过这种累积分析，观察到不同工具之间的差异：Byos和SpectroMine在最小偏差的定量准确性方面表现出色，FragPipe提供高精度和可量化性，PEAKS提供深度蛋白质覆盖，Mascot具有很强的真实性，MaxQuant具有中等鉴定性能，在较低的峰值水平上具有较大的可变性。本研究建立了一个严格的、数据驱动的工具基准框架，并为选择适合生物制药开发中HCP监测的质谱/质谱工具提供指导。

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引用次数: 0

Nanoplasmonic sensing as a rapid and sensitive methodology to investigate tolvaptan loaded plant-derived nanovesicles and liposomes 纳米等离子体传感作为一种快速、灵敏的方法来研究负载tolvaptan的植物源纳米囊泡和脂质体

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-06-01 Epub Date: 2025-01-06 DOI: 10.1016/j.jpbao.2025.100052

Shishir Jaikishan , Ramila Mammadova , Rui Chen , Feby Pratiwi , Gabriella Pocsfalvi , Seppo J. Vainio , Susanne K. Wiedmer

Plant-derived nanovesicles (PDNVs) are potential next generation carriers for drug delivery. However, the systemic incorporation of drugs into PDNVs and their quality control still needs extensive research. Previous works showed that Solanum lycopersicum (tomato) fruit is an excellent resource for the high yield manufacturing of tomato PDNVs. Tomato PDNVs have anti-inflammatory activity in vitro which could be further increased by the loading of a lipophilic natural compound, like curcumin. Recently, tolvaptan, a synthetic selective vasopressin V2-receptor antagonist drug was also successfully loaded into tomato PDNVs. In this work, we have advanced the analysis of native and loaded PDNVs and compared them with liposomes using nanoplasmonic sensing (NPS). Tolvaptan was loaded into liposomes composed of phosphatidyl choline (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and 1,2-palmitoyl-oleoyl-sn-glycero-3-phosphoserine with and without cholesterol. In addition to NPS, micro differential scanning calorimetry was used to get a deeper understanding of the interactions between tolvaptan and the various liposome compositions. The result of the comparative NPS study showed that tolvaptan can be successfully incorporated both into PDNVs and liposomes of different compositions. The PDNV/tolvaptan and liposome/tolvaptan systems were found to be stable. Due to the low water solubility of tolvaptan, the developed PDNV/tolvaptan or liposome/tolvaptan nanoparticle complexes may present a novel and effective strategy for nanodrug delivery.

植物源性纳米囊泡（pdnv）是潜在的下一代药物递送载体。然而，药物系统入药pdnv及其质量控制仍需要广泛的研究。前期研究表明，番茄果实是生产番茄pdnv的优良资源。番茄pdnv在体外具有抗炎活性，可以通过加载亲脂性天然化合物（如姜黄素）进一步增强。最近，合成的选择性抗利尿激素v2受体拮抗剂托伐普坦也成功地装载到番茄pdnv中。在这项工作中，我们进一步分析了天然pdnv和负载pdnv，并使用纳米等离子体传感（NPS）将它们与脂质体进行了比较。Tolvaptan被装入由磷脂酰胆碱（1-棕榈酰-2-油酰- n-甘油-3-磷酸胆碱或1,2-二棕榈酰- n-甘油-3-磷酸胆碱）和1,2-棕榈酰-油酰- n-甘油-3-磷酸丝氨酸（含或不含胆固醇）组成的脂质体中。除了NPS外，微差扫描量热法还被用于更深入地了解托伐普坦与各种脂质体组成之间的相互作用。对比NPS研究结果表明，托伐普坦可以成功地结合到pdnv和不同组成的脂质体中。发现PDNV/tolvaptan和脂质体/tolvaptan体系是稳定的。由于托伐普坦的水溶性较低，所开发的PDNV/托伐普坦或脂质体/托伐普坦纳米颗粒复合物可能是一种新的有效的纳米药物递送策略。

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引用次数: 0

Is surface-enhanced Raman spectroscopy (SERS) a good alternative to separation techniques for nicotine dosage in e-liquid boosters? 表面增强拉曼光谱（SERS）是电子液体中尼古丁剂量分离技术的一个很好的替代方法吗？

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-06-01 Epub Date: 2025-01-16 DOI: 10.1016/j.jpbao.2025.100054

Charlotte De Bleye , Pierre Beckers , Kevser Kemik , Julie Horne , Kenza Lahrichi , Pierre-Yves Sacré , Philippe Hubert , Eric Ziemons

Since 2014, electronic cigarettes must follow the European Directive on tobacco products. In Belgium, the transposition of this directive requires that nicotine-containing e-liquid boosters cannot exceed a concentration of 20 mg mL⁻¹ to ensure consumers safety. Nowadays, accurate analytical methods available to measure nicotine levels in e-liquid products involve chromatography. The development of alternative analytical tools being faster, greener and adaptable to in-field analyses are therefore required. Surface-enhanced Raman scattering is a spectroscopic technique that significantly enhances inherent Raman scattering signals, improving detection limits, when analytes are adsorbed onto metallic nanostructures such as gold nanoparticles (AuNPs). This study introduces new SERS methods for quantifying nicotine in e-liquid boosters using two different Raman spectrophotometers based on a transmission (SETRS) and a backscattering detection mode. The transmission Raman spectrophotometer has a better sample representativity, which is very interesting to perform SERS on liquids samples, and an autosampler offering facilities for routine analyses as a benchtop equipment while the second spectrophotometer was a handheld Raman device allowing to expand the use of the developed SERS method to in-field analyses. These SERS analyses were performed using lab-synthetized AuNps and by adding an isotope-edited internal standards (IEISs) being nicotine-d4 to mitigate some repeatability issues. These methods were finally validated according to the ICH Q2 (R2) guidelines for a working range from 100 to 300 µg L⁻¹ of nicotine concentrations using a total error risk-based approach considering the acceptance limits fixed at 15 % and a risk level of 5 %.

自2014年以来，电子烟必须遵守欧洲烟草产品指令。在比利时，该指令的转换要求含有尼古丁的电子液体增强剂的浓度不能超过20 mg mL−1，以确保消费者的安全。目前，用于测量电子液体产品中尼古丁含量的准确分析方法包括色谱法。因此，需要开发更快、更环保、更适合现场分析的替代分析工具。表面增强拉曼散射是一种光谱技术，当分析物被吸附在金属纳米结构（如金纳米颗粒）上时，可以显著增强固有的拉曼散射信号，提高检测限。本研究介绍了两种不同的基于透射（SETRS）和后向散射检测模式的拉曼分光光度计用于定量电子液体助推器中尼古丁的新SERS方法。透射拉曼分光光度计具有更好的样品代表性，这对于在液体样品上执行SERS是非常有趣的，并且自动进样器提供常规分析设施作为台式设备，而第二个分光光度计是手持式拉曼设备，允许将开发的SERS方法扩展到现场分析。这些SERS分析使用实验室合成的AuNps进行，并通过添加同位素编辑的内标（IEISs）尼古丁-d4来减轻一些可重复性问题。这些方法最终根据ICH Q2 （R2）指南进行验证，尼古丁浓度的工作范围为100至300 µg L−1，采用基于总误差风险的方法，考虑可接受限度固定为15 %，风险水平为5 %。

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引用次数: 0

A compendium of noncoding RNAs as biomarkers in Type 2 Diabetes Mellitus 非编码rna作为2型糖尿病生物标志物的综述

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-06-01 Epub Date: 2025-01-30 DOI: 10.1016/j.jpbao.2025.100057

Manjusha Sita Akella, Angel Mendonca, Thanikes Manikandan, Dhananjay Sateesh, Akshitha Rajesh Swaminathan, Disha Parameshwaran, Manishika Gupta, Sujatha Sundaresan

Diabetes Mellitus (DM) is among the most widespread multifactorial disorders worldwide, defined by increased plasma glucose levels. Type 2 Diabetes Mellitus (T2DM) is the most prevalent and common form of diabetes mellitus. T2DM is a metabolic condition characterized by abnormal blood glucose levels, insulin resistance in target tissues, and a reduced mass and function of islet β cells. Highlighting the significance of investigating new biomarkers, particularly during the initial stages of development, noncoding RNAs (ncRNAs) have been identified as valuable resources for T2DM. NcRNAs are a class of RNAs found in humans that play significant roles in epigenetics and in regulating post-transcriptional gene expression. Since they function as regulatory molecules, upon base pairing with the mRNA, they exhibit post-transcriptional alterations in the signaling cascade within the cells by regulating the expression of multiple targets simultaneously. Small non-coding RNAs (sncRNAs) and long non-coding RNAs (lncRNAs) are the two primary categories of non-coding RNAs. Several studies have shown that sncRNAs and lncRNAs have evolved as potential biomarkers in T2DM. This review focuses on non-coding RNAs as biomarkers for T2DM and their role in preventing chronic complications.

糖尿病（DM）是世界范围内最广泛的多因素疾病之一，其定义为血浆葡萄糖水平升高。2型糖尿病（T2DM）是最常见的糖尿病。T2DM是一种代谢疾病，其特征是血糖水平异常，靶组织胰岛素抵抗，胰岛β细胞质量和功能减少。非编码rna （ncrna）已被确定为T2DM的宝贵资源，这突出了研究新的生物标志物的重要性，特别是在发展的初始阶段。NcRNAs是一类在人类中发现的rna，在表观遗传学和调控转录后基因表达中起着重要作用。由于它们具有调节分子的功能，在与mRNA进行碱基配对后，它们通过同时调节多个靶标的表达，在细胞内的信号级联中表现出转录后的改变。小非编码rna （Small non-coding rna, sncRNAs）和长非编码rna （long non-coding rna, lncRNAs）是非编码rna的两大类。一些研究表明，sncrna和lncrna已发展成为T2DM的潜在生物标志物。本文综述了非编码rna作为2型糖尿病的生物标志物及其在预防慢性并发症中的作用。

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引用次数: 0

Laser-induced graphene electrodes obtained by direct laser writing for pharmaceutical and biomedical analysis 激光诱导石墨烯电极，直接激光写入，用于制药和生物医学分析

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-06-01 Epub Date: 2025-03-01 DOI: 10.1016/j.jpbao.2025.100069

Amal Rabti , Sabrine Baachaoui , Mohamed Zouari , Noureddine Raouafi

Laser-induced graphene (LIG), also referred to as laser-ablated graphene (LAG), laser-scribed graphene (LSG), laser-produced graphene (LPG), laser-engineered graphene (LEG), and laser-derived graphene (LDG), has emerged as a versatile material for the development of high-performance electrodes that exhibit unique properties, such as high electrical conductivity, large surface area, chemical stability, and ease of functionalization. These characteristics render LIG electrodes particularly suitable for pharmaceutical and biomedical applications where rapid, sensitive, and reliable analytical methods are required. This review presents a comprehensive overview of recent advancements in the utilization of graphene electrodes for pharmaceutical and biomedical applications. They encompass their fabrication processes, surface modifications with nanomaterials and biomolecules, and the principal analytical techniques employed, including electrochemical sensing, biosensing, and drug monitoring. Particular emphasis is placed on the integration of LIG electrodes into point-of-care devices for clinical diagnostics and therapeutic drug monitoring, as well as their role in detecting biomarkers and pharmaceutical residues. Furthermore, the challenges and future perspectives for LIG electrodes in achieving widespread adoption in the biomedical and pharmaceutical fields are examined, underscoring the need for improved scalability, selectivity, and regulatory compliance. This review elucidates the transformative potential of LIG-based technologies for addressing emerging healthcare challenges through innovative and cost-effective analytical solutions.

激光诱导石墨烯（LIG），也被称为激光烧烧石墨烯（LAG）、激光刻写石墨烯（LSG）、激光生产石墨烯（LPG）、激光工程石墨烯（LEG）和激光衍生石墨烯（LDG），已经成为一种多功能材料，用于开发高性能电极，具有高导电性、大表面积、化学稳定性和易于功能化等独特性能。这些特性使得LIG电极特别适用于需要快速、敏感和可靠分析方法的制药和生物医学应用。本文综述了石墨烯电极在制药和生物医学应用方面的最新进展。它们包括它们的制造过程，纳米材料和生物分子的表面修饰，以及所采用的主要分析技术，包括电化学传感，生物传感和药物监测。特别强调的是将LIG电极整合到临床诊断和治疗药物监测的护理点设备中，以及它们在检测生物标志物和药物残留方面的作用。此外，研究了LIG电极在生物医学和制药领域广泛应用所面临的挑战和未来前景，强调了提高可扩展性、选择性和法规遵从性的必要性。这篇综述阐明了基于lige的技术通过创新和具有成本效益的分析解决方案解决新兴医疗保健挑战的变革潜力。

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引用次数: 0

Innovative QSRR modeling approach for the development of an ultra-sensitive LC-MS/MS method for trace analysis of N-nitrosamines 创新的QSRR建模方法用于开发n -亚硝胺痕量分析的超灵敏LC-MS/MS方法

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-06-01 Epub Date: 2025-02-19 DOI: 10.1016/j.jpbao.2025.100064

Yue Zhang, Sabah Houari, Thomas Van Laethem, Amandine Dispas, Eric Ziemons, Philippe Hubert, Cédric Hubert

To address regulatory concerns regarding N-nitrosamine contamination in pharmaceutical products, generic LC-MS/MS methods for determining N-nitrosamines were developed using an innovative in silico approach based on Quantitative Structure Retention Relationship modeling (QSRR). The development process included screening and optimization phases, offering flexibility in targeting N-nitrosamines and addressing the challenges related to the matrix effect. This methodology represents a significant advancement in method development. Among the developed methods, a highly sensitive and accurate LC-MS/MS method was successfully validated to simultaneously determine 5 small-molecule N-nitrosamine impurities in tablets, which was used in the present proof-of-concept study. The validation followed the ICH Q2 (R2) guidelines, employing a combined approach for accuracy and precision based on total error risk-based methodology. The method was validated to function as both an impurity limit test and a quantitative method. Validation results demonstrated adequate quantitative performance of the method, establishing a validated dosing range from 1 to 30 ng/mL for all N-nitrosamines. The estimated detection limit ranged from 0.75 pg/mL to 0.02 ng/mL. The detection and quantification limits for each N-nitrosamine met the EMA N-nitrosamine investigation approach requirements. Moreover, both are always below 10 % of their respective acceptable limit in the studied finished product formulation. This proposed method is suitable for investigating small-molecule N-nitrosamines in pharmaceutical products and also provides a starting point for further method development, particularly for the determination of newly identified small-molecule N-nitrosamines and drug-substance-related N-nitrosamines.

为了解决药品中n -亚硝胺污染的监管问题，使用基于定量结构保留关系模型（QSRR）的创新硅方法开发了通用的LC-MS/MS检测n -亚硝胺的方法。开发过程包括筛选和优化阶段，提供了针对n -亚硝胺的灵活性，并解决了与基质效应相关的挑战。这种方法代表了方法开发的重大进步。其中，高效液相色谱-质谱联用（LC-MS/MS）方法可同时测定片剂中5种小分子n -亚硝胺类杂质，并用于概念验证研究。验证遵循ICH Q2 （R2）指南，采用基于总误差风险方法的准确度和精密度相结合的方法。结果表明，该方法既可作为杂质限检方法，又可作为定量方法。验证结果表明该方法具有足够的定量性能，建立了所有n -亚硝胺的有效剂量范围为1至30 ng/mL。估计检出限范围为0.75 pg/mL至0.02 ng/mL。各n -亚硝胺的检出定量限均符合EMA n -亚硝胺调查方法要求。此外，在研究的成品配方中，两者始终低于各自可接受限度的10% %。该方法适用于研究药品中的小分子n -亚硝胺，也为进一步的方法开发提供了起点，特别是对于新鉴定的小分子n -亚硝胺和与药物相关的n -亚硝胺的测定。

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引用次数: 0

Nanohybrids based on multi-walled carbon nanotubes and MOF-199: Advantages on the electrochemical reduction of hydrogen peroxide and sensing applications 基于多壁碳纳米管和MOF-199的纳米杂化材料：过氧化氢电化学还原及传感应用的优势

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-06-01 Epub Date: 2025-02-18 DOI: 10.1016/j.jpbao.2025.100066

Pablo A. Gallay , Virginia M. Vaschetti , Facundo Aghemo , Pablo R. Dalmasso , Gustavo A. Rivas

We report the advantages of a nanohybrid obtained through the integration of multi-walled carbon nanotubes (MWCNTs) and MOF-199 by sono-synthesis. The resulting nanohybrid presents important synergic effects on the catalytic reduction of hydrogen peroxide due to the facilitated regeneration of the catalytic center in the presence of the interconnected carbon nanomaterial. Glassy carbon electrodes (GCE) modified with this hybrid nanomaterial dispersed in Nafion allowed the sensitive quantification of hydrogen peroxide: linear range between 5.0 × 10⁻⁶ M and 7.5 × 10⁻⁵ M (R² = 0.997), with a sensitivity of (128 ± 3) x 10² µA M⁻¹, a detection limit of 2 µM, and a reproducibility of 8.0 % for the same nanohybrid and 5 different electrodes allowing the competitive electrochemical determination of hydrogen peroxide. The sensor was successfully used for the quantification of this important analyte in diverse commercial samples (milk, human serum, contact lens disinfecting solution, and mouthwash).

我们报道了多壁碳纳米管（MWCNTs）和MOF-199通过声合成得到的纳米杂化材料的优点。所得到的纳米杂化物对过氧化氢的催化还原表现出重要的协同效应，这是因为在相互连接的碳纳米材料的存在下，催化中心的再生更加容易。玻碳电极(GCE)修改该混合纳米材料分散在全氟磺酸允许过氧化氢的敏感量化:线性范围介于5.0 × 10−6 M和7.5 × 10−5 M (R2 = 0.997)的灵敏度(128 ± 3)x 102µ M−1、2的检测极限 µM和8.0 %的再现性相同的nanohybrid和5种不同电极允许竞争电化学测定过氧化氢。该传感器已成功用于多种商业样品（牛奶、人血清、隐形眼镜消毒液和漱口水）中这一重要分析物的定量。

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引用次数: 0

Development of a new green gas chromatographic method for the determination of zolmitriptan in pure and pharmaceutical preparations 建立一种新的绿色气相色谱法测定纯制剂和制剂中唑米曲坦的含量

Journal of Pharmaceutical and Biomedical Analysis Open

Pub Date : 2025-06-01 Epub Date: 2025-01-30 DOI: 10.1016/j.jpbao.2025.100059

Reem Hasan Obaydo R.H.Obaydo , Abdulsalam Ashkar , Raneem Khayyat , Salem Alhamdan , Hadeel Kallas , Mohammad Kharrat , Amir Alhaj Sakur

A simple, accurate, and environmentally friendly method for determining raw zolmitriptan (ZMT) and its dosage form (tablets) was developed and validated using capillary gas chromatography (GC). Methanol was used to prepare the solutions of the standard and the sample, and instrument parameters were optimized with a programmed temperature ramp ranging from 230 to 290 °C, achieving a total run time of 9.0 min. The retention times for Metronidazole Benzoate (MNZB), the internal standard, and ZMT were found to be 4.89 and 8.11 min, respectively. GC separation was performed with a TRB-5 capillary column (30 m × 0.25 mm, 0.25 μm) with a 0.5 μL injection in splitless mode. The calibration curve was linear when testing a range of concentrations of 6.0–80.0 μg/mL. The limits of detection (LOD) and quantification (LOQ) were determined to be 0.53 and 1.77 μg/mL, respectively, with a correlation coefficient (R²) greater than 0.999. The method proposed was efficiently applicable to analyze pure ZMT and in tablets, showing no interference from other components of the pharmaceutical preparation. Validation of the method was done per ICH guidelines, with all parameters meeting the required acceptance criteria. Additionally, evaluation of the greenness and sustainability of the GC method proposed was performed using AGREE, modified GAPI, and the RGB fast model.

建立了一种简单、准确、环保的测定佐米曲坦（ZMT）原料药及其剂型（片剂）的方法，并利用毛细管气相色谱（GC）进行了验证。用甲醇制备标准品和样品溶液，并在230 ~ 290℃的程序升温范围内优化仪器参数，总运行时间为9.0 min。苯甲硝唑（MNZB）、内标、ZMT的保留时间分别为4.89和8.11 min。色谱柱为TRB-5毛细管柱（30 m × 0.25 mm, 0.25 μm），进样量为0.5 μL，无分裂。在6.0 ~ 80.0 μg/mL范围内，校准曲线呈线性。检测限（LOD）和定量限（LOQ）分别为0.53和1.77 μg/mL，相关系数（R²）均大于0.999。该方法适用于ZMT纯品和片剂的分析，不受制剂中其它成分的干扰。方法的验证按照ICH指南进行，所有参数符合要求的验收标准。此外，采用AGREE、改进GAPI和RGB快速模型对所提出的GC方法的绿色度和可持续性进行了评价。

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