Rapid Communications in Mass Spectrometry最新文献_第6页

Establishment and Validation of High-Performance Liquid Chromatography—Tandem Mass Spectrometry for Simultaneous Assessment of Amlodipine and Indapamide in Human Plasma 高效液相色谱-串联质谱法同时测定人血浆中氨氯地平和吲达帕胺含量的建立与验证

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-22 DOI: 10.1002/rcm.10131

Duc Tuan Nguyen, Thu Le Anh Do, Sil Thanh Nguyen, Thi Anh Huynh Huynh, Vo Thi Kim Khuyen, Tho Vinh Minh Chau Do

Background

Hypertension is a major cause of premature death worldwide despite the availability of a number of antihypertensive medication monotherapies. Therefore, several polytherapies have been prescribed, among which the combination of amlodipine with indapamide is often the preferred choice to control blood pressure, especially in the elderly, because of its efficacy and safety. To ensure the quality of this combination drug, a versatile procedure for the simultaneous quantification of components is required. Thus, this study aims to develop a liquid chromatography - tandem mass spectrometric procedure and validate according to FDA and EMA guidelines to determine amlodipine and indapamide in human plasma.

Methods

A liquid–liquid extraction with tert-butyl methyl ether and ethyl acetate (1:1) was applied to extract the compounds. Amlodipine was ionized with positive electrospray ionization and detected by multiple reaction monitoring mode, while indapamide was ionized with negative electrospray ionization and detected by selected ion monitoring mode. Samples were chromatographically analyzed on a C18 column (150 × 4.6 mm; 3.5 μm), eluted by the mobile phase of methanol and 0.025% formic acid (90:10, v/v).

Results

Linearity ranged from 0.29- to 17.14-ng/mL amlodipine, from 1.14- to 68.57-ng/mL indapamide. The lower limit of quantitation of amlodipine and indapamide is 0.29- and 1.14-ng/mL, respectively. The validation using furosemide as an internal standard showed that the specificity, intra- and interday precision and accuracy, matrix effect, sample carryover, dilution, and stability were in the acceptable range.

Conclusions

The method met validation criteria of US-FDA and EMA guidelines, thereby recommended for application in in vivo bioavailability and bioequivalence assessment of fixed-dose combinations of amlodipine with indapamide.

背景：尽管有许多抗高血压药物单一疗法，高血压仍是世界范围内过早死亡的主要原因。因此，有几种综合疗法被开处方，其中氨氯地平与吲达帕胺联用往往是控制血压的首选，特别是在老年人中，因为它的有效性和安全性。为了保证这种联合药物的质量，需要一种通用的同时定量成分的方法。因此，本研究旨在建立一种液相色谱-串联质谱方法，并根据FDA和EMA的指南进行验证，以测定人血浆中的氨氯地平和吲达帕胺。方法采用叔丁基甲基醚和乙酸乙酯（1:1）液液萃取法提取。氨氯地平采用正电喷雾电离，采用多反应监测模式检测；吲达帕胺采用负电喷雾电离，采用选择离子监测模式检测。样品在C18色谱柱（150 × 4.6 mm; 3.5 μm）上进行色谱分析，流动相为甲醇和0.025%甲酸（90:10,v/v）。结果氨氯地平线性范围为0.29 ~ 17.14 ng/mL，吲达帕胺线性范围为1.14 ~ 68.57 ng/mL。氨氯地平和吲达帕胺的定量下限分别为0.29 ng/mL和1.14 ng/mL。以速尿为内标进行验证，特异性、内、日间精密度和准确度、基质效应、样品携带、稀释度、稳定性均在可接受范围内。结论该方法符合US-FDA和EMA指南的验证标准，可用于氨氯地平与吲达帕胺固定剂量联合使用的体内生物利用度和生物等效性评价。

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引用次数: 0

Comprehensive Metabolic Profiling of Resigratinib, a Novel FGFR Inhibitor, Using Integrated LC–MS/MS and LC-Orbitrap-HRMS 基于LC-MS/MS和LC-Orbitrap-HRMS的新型FGFR抑制剂瑞格替尼综合代谢谱分析

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-17 DOI: 10.1002/rcm.10141

Xiaoxia An, Yanting Mao, Ali Fan, Ting Ma

Rationale

Resigratinib, a potent fibroblast growth factor receptor (FGFR) inhibitor, is under clinical development for solid tumors such as cholangiocarcinoma. However, data on its hepatic metabolism remain limited. To support further development, this study aimed to characterize its in vitro metabolism using rat, dog, monkey, and human liver microsomes.

Methods

A sensitive and robust liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was validated for quantifying resigratinib in liver microsomes. Metabolite characterization was performed using LC coupled with benchtop Orbitrap high-resolution mass spectrometry (LC-Orbitrap-HRMS) in full-scan MS/dd-MS² and parallel reaction monitoring (PRM). This approach enabled accurate mass measurement, chemical formula assignment, and structural elucidation via MS² fragmentation interpretation.

Results

The established method exhibited excellent linearity over the concentration range of 1.0–1000 nM. Resigratinib displayed low clearance in dog (t_1/2 = 91.2 min), intermediate clearance in rat (t_1/2 = 20.2 min), and high clearance in monkey (t_1/2 = 6.8 min) and human (t_1/2 = 14.0 min) systems. Ten metabolites were identified, with M3 (bis-demethylation), M5 (O-demethylation), and M9 (N-demethylation) identified as the major metabolites. Recombinant human cytochrome P450 enzyme analysis and chemical inhibition studies indicated that CYP3A4 is the predominant enzyme responsible for resigratinib metabolism.

Conclusion

This study presents the first integrated analytical approach, combining LC–MS/MS and LC-Orbitrap-HRMS, for the in vitro metabolic assessment of resigratinib. The observed metabolic profiles provide an essential foundation for further toxicological and clinical investigations.

理由：瑞格替尼是一种有效的成纤维细胞生长因子受体（FGFR）抑制剂，目前正处于用于胆管癌等实体肿瘤的临床开发阶段。然而，关于其肝脏代谢的数据仍然有限。为了支持进一步的开发，本研究旨在用大鼠、狗、猴和人的肝微粒体来表征其体外代谢。方法：建立高效液相色谱-串联质谱（LC-MS/MS）定量分析肝微粒体中瑞格瑞替尼的方法。在全扫描MS/dd-MS2和平行反应监测（PRM）中，使用LC耦合台式Orbitrap高分辨率质谱（LC-Orbitrap- hrms）进行代谢物表征。这种方法可以实现精确的质量测量，化学式分配，并通过MS2碎片解释进行结构解释。结果：所建立的方法在1.0 ~ 1000 nM的浓度范围内线性良好。瑞格替尼在犬体内清除率低（t1/2 = 91.2 min），在大鼠体内清除率中等（t1/2 = 20.2 min），在猴体内清除率高（t1/2 = 6.8 min），在人体内清除率高（t1/2 = 14.0 min）。鉴定出10种代谢物，其中M3（双去甲基化）、M5 （o -去甲基化）和M9 （n -去甲基化）是主要代谢物。重组人细胞色素P450酶分析和化学抑制研究表明，CYP3A4是瑞格替尼代谢的主要酶。结论：本研究首次采用LC-MS/MS和LC-Orbitrap-HRMS相结合的综合分析方法进行瑞格替尼体外代谢评价。观察到的代谢谱为进一步的毒理学和临床研究提供了必要的基础。

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引用次数: 0

Targeted Screening for Active Flavonoids From Medicinal Extracts to Trap Methylglyoxal: Scutellaria barbata Herba as a Case Study 药用提取物中活性黄酮类化合物捕集甲基乙二醛的靶向筛选——以黄芩为例

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-16 DOI: 10.1002/rcm.10129

Qingrui Zhang, Xiaoxiao Zhang, Qibao Jiang, Xiaoge Li, Miaomiao Jiang

Rationale

Methylglyoxal (MGO) is a highly reactive carbonyl species that modifies proteins, leading to the formation of advanced glycation end products (AGEs), which contribute to diseases such as diabetes and cardiovascular disorders. Certain flavonoids, including quercetin and luteolin, can trap MGO, thereby preventing AGE formation. However, traditional screening methods for identifying MGO-trapping flavonoids are inefficient and not suitable for high-throughput analysis.

Methods

In this study, a novel screening approach was developed utilizing electrospray ionization mass spectrometry with data-dependent acquisition and neutral loss scanning (ESI-DDA-NL). Data-dependent acquisition enhances the quality of tandem mass spectra. By analyzing MS/MS fragmentation patterns, flavonoids that had formed adducts with MGO were identified based on a characteristic 72.0206-Da mass increase and a neutral loss fragment (C3H4O2, 72.0206 Da).

Results

This approach enabled the rapid identification of 10 active flavonoids from Scutellaria barbata herba extract. Among these, luteolin, quercetin, naringenin, and apigenin were already known MGO-trapping agents, while scutellarein, hispidulin, nepetin, 6-methoxyerythrictyol, 6-methoxynaringenin, and 4'-hydroxywogonin were newly identified as MGO-trapping agents. Scutellarein and hispidulin were further validated through individual MGO reactions.

Conclusions

ESI-DDA-NL is an effective method for screening active flavonoids in traditional Chinese medicine that are capable of trapping MGO.

理由：甲基乙二醛（MGO）是一种高活性的羰基物质，可以修饰蛋白质，导致晚期糖基化终产物（AGEs）的形成，从而导致糖尿病和心血管疾病等疾病。某些类黄酮，包括槲皮素和木犀草素，可以捕获氧化镁，从而防止AGE的形成。然而，传统的黄酮类化合物筛选方法效率低，不适合高通量分析。方法：在本研究中，利用电喷雾电离质谱与数据依赖获取和中性损失扫描（ESI-DDA-NL）开发了一种新的筛选方法。数据依赖性采集提高了串联质谱的质量。通过MS/MS分析，黄酮类化合物与MGO形成加合物的特征特征为质量增加72.0206-Da和中性损失片段（C3H4O2, 72.0206 Da）。结果：该方法可快速鉴定黄芩提取物中10种活性黄酮类化合物。其中木犀草素、槲皮素、柚皮素和芹菜素是已知的mgo捕获剂，而灯芯草素、hispidulin、nepetin、6-甲氧基赤藓醇、6-甲氧基柚皮素和4'-羟基枸杞素是新发现的mgo捕获剂。通过单独的MGO反应进一步验证了Scutellarein和hispidulin。结论：ESI-DDA-NL是筛选能捕获MGO的中药活性黄酮类化合物的有效方法。

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引用次数: 0

A Pilot Study Using Microbial Glycolipid Signatures to Diagnose Nosocomial Ventriculitis 利用微生物糖脂特征诊断院内脑室炎的初步研究。

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-15 DOI: 10.1002/rcm.10138

Ian P. O'Keefe, Nicole Putnam, Robert K. Ernst, James B. Doub

Rationale

Ventriculitis is a life-threatening infectious condition that requires rapid pathogen identification. Conventional diagnostic methods often require 24–48 h of ex vivo culture. The aim of this study was to evaluate a novel MALDI-TOF MS approach for analyzing glycolipids for species-level pathogen identification directly from cerebral spinal fluid (CSF).

Methods

Pathogen identification was conducted with the fast lipid analysis technique (FLAT), combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). In this pilot study, 12 CSF samples were analyzed, comprising six culture-positive and six true negative specimens. The FLAT method was applied to 1 mL of CSF from each sample, enabling pathogen identification within approximately 1.5 h.

Results

FLAT was performed directly on CSF in under 2 h. Successful genus-level identification for all six culture-positive samples was achieved, with five out of six correctly identified at the species level. Importantly, culture-negative samples did not produce any pathogen-associated glycolipid fingerprints, indicating the method's specificity.

Conclusion

This study highlights the potential of FLAT followed by MALDI-TOF MS as a valuable tool for expediting ventriculitis pathogen identification. By bypassing the need for culture and delivering results in about an hour, this approach could significantly reduce turnaround times and potentially improve patient outcomes.

理由：脑室炎是一种危及生命的传染病，需要快速鉴定病原体。传统的诊断方法通常需要24-48小时的体外培养。本研究的目的是评估一种新的MALDI-TOF质谱方法，用于直接从脑脊液（CSF）中分析糖脂，用于物种水平的病原体鉴定。方法：采用快速脂质分析技术（FLAT）结合基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）对病原菌进行鉴定。在这项初步研究中，分析了12份脑脊液样本，包括6份培养阳性和6份真阴性样本。每个样品取1 mL脑脊液，采用FLAT方法，在约1.5 h内鉴定病原体。结果：在2 h内直接对脑脊液行FLAT。对所有6个培养阳性样本进行了成功的属水平鉴定，6个样本中有5个在物种水平上得到了正确鉴定。重要的是，培养阴性样品没有产生任何与病原体相关的糖脂指纹，表明该方法的特异性。结论：本研究强调了FLAT联合MALDI-TOF MS作为加速脑室炎病原体鉴定的有价值工具的潜力。通过绕过培养的需要，在大约一个小时内交付结果，这种方法可以显着减少周转时间，并有可能改善患者的治疗效果。

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引用次数: 0

Identification of the In Vitro and In Vivo Metabolites of Chrysotoxine Using Liquid Chromatography Combined With Benchtop Orbitrap High-Resolution Mass Spectrometry 液相色谱结合台式轨道阱高分辨率质谱法鉴定黄曲毒素体内体外代谢产物

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-10 DOI: 10.1002/rcm.10137

Chengzhen Guan, Yiqiang An, Meiling Wan

Rationale

Chrysotoxine, a bibenzyl derivative from the stems of Dendrobium medicinal herbs, has recently emerged as a promising therapeutic candidate for cervical cancer. This study aimed to characterize chrysotoxine metabolites across multiple hepatocyte species and in rat urine.

Methods

Metabolites were identified and characterized using liquid chromatography coupled with benchtop Orbitrap high-resolution mass spectrometry (LC–Orbitrap–MS/MS) combined with Compound Discoverer software. Structural elucidation relied on accurate mass measurements (mass error < 5 ppm) and comprehensive MS² fragmentation pattern interpretation.

Results

Twelve distinct metabolites were structurally identified. Among these, M4, M6, M7, M8, M10, M11, and M12 are newly reported. Metabolic transformations occurred via five principal pathways: hydroxylation, demethylation, glucuronidation, sulfation, and glutathione (GSH) conjugation. Cross-species analysis of hepatocytes revealed direct glucuronidation as the predominant metabolic reaction. Urinary excretion profiles in rats identified hydroxylated (M9) and glucuronidated (M11) metabolites as the major elimination products. During the metabolism, chrysotoxine can be metabolized into quinone methide and ortho quinone intermediates that can be conjugated with GSH, forming the adducts M1, M2, M3, and M5.

Conclusions

This study delineates chrysotoxine metabolites in vitro and in vivo, providing critical insights for further pharmacokinetic and toxicity assessments.

理由：金曲毒素是一种从石斛属草本植物茎中提取的联苯衍生物，最近被认为是治疗宫颈癌的一种有希望的候选药物。本研究旨在表征黄曲毒素在多种肝细胞和大鼠尿液中的代谢物。方法：采用液相色谱-台式Orbitrap高分辨率质谱（LC-Orbitrap-MS/MS）结合Compound Discoverer软件对代谢物进行鉴定和表征。结构解释依赖于精确的质量测量（质量误差2破碎模式解释）。结果：在结构上鉴定出12种不同的代谢物。其中M4、M6、M7、M8、M10、M11、M12为新报道。代谢转化通过五个主要途径发生：羟基化、去甲基化、葡萄糖醛酸化、磺化和谷胱甘肽（GSH）偶联。肝细胞的跨物种分析显示直接葡萄糖醛酸化是主要的代谢反应。在大鼠的尿液排泄中发现羟基化（M9）和葡萄糖醛酸化（M11）代谢物是主要的消除产物。在代谢过程中，黄曲毒素被代谢成醌类和邻醌类中间体，与谷胱甘肽偶联，形成加合物M1、M2、M3和M5。结论：本研究描述了黄曲毒素在体外和体内的代谢产物，为进一步的药代动力学和毒性评估提供了重要的见解。

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引用次数: 0

Exploring the Fragmentation of Sodiated Species Involving Covalent-Bond Cleavages for Metabolite Characterization. 探索涉及共价键切割的碱化物种的碎片，用于代谢物表征。

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-08 DOI: 10.1002/rcm.10133

Annelaure Damont, Ekaterina Darii, Chenqin Cao, Anaïs Legrand, Alain Perret, Sylvain Dechaumet, Amina S Woods, Christophe Junot, Jean-Claude Tabet, François Fenaille

Rationale: Electrospray (ESI), the most popular desorption/ionization technique used in mass spectrometry-based metabolomics, generates both protonated and deprotonated molecules, as well as adduct ions, sodium being the most frequent monoatomic cation entering their composition. With the spread and generalization of untargeted data-dependent and independent tandem mass spectrometry experiments, considering product ion spectra of sodium-containing entities appears relevant to complement fragmentation information of their protonated and deprotonated counterparts.

Methods: Solutions of pure standards, mainly amino and organic acids, were prepared at 1 μg/mL and injected either by direct infusion or by flow-injection prior to ESI-MS/MS analysis. Product ion spectra of (de)protonated and sodiated molecules were recorded both in positive and negative modes on Orbitrap instruments under both non-resonant and resonant excitation conditions. Various normalized collision energies (NCE) were applied and the resulting collisional spectra were analyzed.

Results: Examination of the resulting collisional spectra clearly revealed that fragmentation of sodiated ion species may produce spectra significantly different from [M + H]⁺ or [M - H]^-. They can be highly informative and result from specific fragmentation mechanisms based on covalent bond cleavages (CBCs) compared to protonated or deprotonated molecules. These specific CBCs involving sodium retention either in product ions or in neutral losses have been investigated and seem to occur when the sodium cation is involved in an ion-ion type interaction within the structure.

Conclusions: Overall, we show, using representative examples of biologically relevant metabolites, the benefits of considering MS/MS data generated from sodiated entities, in addition to [M + H]⁺ and [M - H]^- collisional data, to improve metabolite identification. The differentiation of four positional isomers is a striking illustration of the power of fragmentation information obtained with species of the [M - 2H + Na]^- form. Considering the number of metabolites featuring chemical groups capable of interacting with Na⁺, systematic integration of these data into annotation workflows should be considered.

原理：电喷雾（ESI）是最流行的解吸/电离技术，用于基于质谱的代谢组学，产生质子化和去质子化分子，以及加合离子，钠是最常见的单原子阳离子进入它们的组成。随着非靶向数据依赖和独立串联质谱实验的普及和推广，考虑含钠实体的产物离子谱似乎与补充其质子化和去质子化对应物的碎片化信息有关。方法：制备以氨基酸和有机酸为主的纯标准液，浓度为1 μg/mL，采用直注或流动注射两种方式注射，然后进行ESI-MS/MS分析。在非共振和共振激发条件下，在Orbitrap仪器上记录了（去）质子化和碱化分子在正负模式下的生成物离子谱。应用了各种归一化碰撞能量（NCE），并对得到的碰撞谱进行了分析。结果：对碰撞光谱的检查清楚地表明，固化离子的破碎可能产生与[M + H]+或[M - H]-明显不同的光谱。与质子化或去质子化分子相比，它们是基于共价键裂解（CBCs）的特定断裂机制而产生的，具有很高的信息量。这些特定的CBCs涉及钠在产物离子或中性损失中的保留，并且似乎发生在钠阳离子参与结构内离子-离子型相互作用时。结论：总的来说，我们通过生物学相关代谢物的代表性例子表明，除了[M + H]+和[M - H]-碰撞数据外，考虑从中介实体生成的MS/MS数据可以改善代谢物鉴定。四种位置异构体的分化是[M - 2H + Na]-形式的物种获得的碎片信息的力量的一个引人注目的说明。考虑到具有能够与Na+相互作用的化学基团的代谢物的数量，应该考虑将这些数据系统地集成到注释工作流程中。

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引用次数: 0

An Optimized Method for Extraction and Detection of Polycyclic Aromatic Hydrocarbons in Soil/Sediment—Based on Gas Chromatography–Tandem Mass Spectrometry 基于气相色谱-串联质谱法的土壤/沉积物中多环芳烃提取与检测优化方法

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-07 DOI: 10.1002/rcm.10115

Ling Wen, Chao Ma, Xiaoli Fu, Yulin Qi, Dietrich A. Volmer

引用次数: 0

Chemical Profiling of Chixiaodou Danggui San Using Liquid Chromatography–Tandem Mass Spectrometry With Data Mining Strategy 基于数据挖掘的液相色谱-串联质谱分析赤小豆当归散的化学性质

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-04 DOI: 10.1002/rcm.10134

Ji Chen, Ting Tan, Yun Luo

Rationale

Chixiaodou Danggui San (CDS), composed of Vignae semen (VS) and Angelicae sinensis radix (ASR), has been utilized for the treatment of hemorrhoids in China. However, the chemical profiling of CDS remains insufficiently explored. Therefore, it is necessary to establish an accurate and rapid method for the chemical profiling of CDS.

Methods

The structure elucidation of natural products using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS), despite its exceptional capabilities, remains limited due to the complexity of mixtures containing hundreds of compounds. In this study, we utilized the UHPLC-QTOF-MS/MS in conjunction with data mining strategy, incorporating diagnostic fragment ions (DFIs) and neutral loss (NL), for the rapid classification and identification of compounds in CDS.

Results

Consequently, 97 chemical compositions were tentatively characterized, comprising 31 flavonoids, 25 triterpenoid saponins, 11 fatty acids, 10 chlorogenic acids, and 20 others. Out of these, 13 were verified using authentic standards. Twenty-one triterpenoid saponins were tentatively characterized as new compounds, which need to be purified, and were identified by NMR data. It is noteworthy that flavonoids and triterpenoid saponins are exclusive to VS, chlorogenic acid is unique to ASR, while fatty acids and other compounds are present in both VS and ASR.

Conclusions

Our findings represent a crucial step in elucidating the active compounds in CDS for the treatment of hemorrhoids.

赤消豆当归散（CDS）是由枳实（VS）和当归（ASR）组成，在中国被用于治疗痔疮。然而，CDS的化学谱分析仍然没有得到充分的探索。因此，有必要建立一种准确、快速的CDS化学谱分析方法。方法利用超高效液相色谱-四极杆飞行时间串联质谱法（UHPLC-QTOF-MS/MS）对天然产物进行结构分析，尽管具有出色的能力，但由于含有数百种化合物的混合物的复杂性，仍然受到限制。在本研究中，我们利用UHPLC-QTOF-MS/MS结合数据挖掘策略，结合诊断片段离子（dfi）和中性损失（NL），对CDS中的化合物进行快速分类和鉴定。结果共鉴定出97种化学成分，其中黄酮类化合物31种，三萜皂苷25种，脂肪酸11种，绿原酸10种，其他化合物20种。其中，13项采用真实标准进行了验证。21个三萜皂苷被初步鉴定为新化合物，需要进行纯化，并通过NMR数据进行了鉴定。值得注意的是，黄酮类和三萜皂苷是紫花苜蓿所特有的，绿原酸是紫花苜蓿所特有的，脂肪酸等化合物在紫花苜蓿和紫花苜蓿中都存在。结论：我们的发现为阐明CDS治疗痔疮的活性化合物迈出了关键的一步。

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引用次数: 0

Suzetrigine in Equestrian Sports: Optimized Extraction and LC-HRMS Detection Strategies 马术运动中的苏三嗪：优化提取及LC-HRMS检测策略

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-04 DOI: 10.1002/rcm.10135

Meleparappil Muhammed Ajeebsanu, Shino Ann Koshy, Abdul Khader Karakka Kal, Michael Benedict Subhahar, Tajudheen K. Karatt, Moses Philip

Rationale

Suzetrigine, a recently approved Na_V1.8 sodium channel blocker, shows strong potential in the treatment of neurological, psychiatric, and pain-related conditions. Its peripheral selectivity enables effective pain management while avoiding central nervous system complications and addiction risks linked to opioid use. Following FDA approval in January 2025, concerns have emerged regarding its possible misuse for performance enhancement in sports, highlighting the need for reliable detection tools in doping control.

Methods

An analytical procedure was designed and validated to detect suzetrigine in equine urine and plasma. Different chromatographic columns, mobile phase compositions, and ionization modes were systematically tested. Extraction efficiency was evaluated using solid-phase extraction (SPE), liquid–liquid extraction (LLE), and dilute-and-inject techniques to identify the most suitable approach for sensitivity and recovery.

Results

Of the various chromatographic columns evaluated, the AQUA C18 column (3.0 μm, 4.6 × 150 mm) exhibited the best separation performance. Among the extraction techniques tested, LLE optimized at specific pH levels and solvent conditions consistently achieved superior recovery rates and lower limits of detection. The fully validated procedure, utilizing high-resolution mass spectrometry, demonstrated excellent sensitivity, reproducibility, and robustness, making it suitable for routine detection of suzetrigine in biological matrices.

Conclusions

The validated approach offers a reliable tool for doping control laboratories to detect suzetrigine in equestrian samples. Beyond equine testing, this protocol provides a methodological framework that can be extended to broader anti-doping programs, supporting the monitoring of emerging substances with misuse potential in sports.

Suzetrigine是最近批准的NaV1.8钠通道阻滞剂，在神经、精神和疼痛相关疾病的治疗中显示出强大的潜力。其外周选择性使有效的疼痛管理，同时避免中枢神经系统并发症和成瘾风险与阿片类药物的使用。在FDA于2025年1月批准后，人们开始担心它可能被滥用于提高运动成绩，这凸显了在兴奋剂控制中需要可靠的检测工具。方法设计并验证了马尿液和血浆中磺胺三嗪的检测方法。系统地测试了不同的色谱柱、流动相组成和电离模式。采用固相萃取（SPE）、液-液萃取（LLE）和稀释-注入技术对提取效率进行了评价，以确定最合适的提取方法的灵敏度和回收率。结果AQUA C18色谱柱（3.0 μm, 4.6 × 150 mm）的分离效果最好。在所测试的提取工艺中，在特定的pH和溶剂条件下优化的LLE提取工艺始终具有较高的回收率和较低的检出限。充分验证的程序，利用高分辨率质谱，表现出优异的灵敏度，再现性和稳健性，使其适用于常规检测生物基质中的苏三嗪。结论该方法为兴奋剂检测实验室检测马术运动员样本中的苏三嗪提供了可靠的工具。除马类检测外，该协议还提供了一个方法框架，可扩展到更广泛的反兴奋剂项目，支持监测体育运动中可能被滥用的新物质。

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引用次数: 0

Open-Source System Suitability: Mass Spectrometry Query Language Lab (MassQLab) 开源系统适用性：质谱查询语言实验室（MassQLab）

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2025-09-02 DOI: 10.1002/rcm.10132

Heather L. Winter, Dylan Johnson, Alan K. Jarmusch

Rationale

Reproducible analytical instrumentation system performance is critical for mass spectrometry, particularly metabolomics, aptly named system suitability testing. We identified a need based on literature reports that stated only 2% of papers performed system suitability testing.

Methods

We report MassQLab, built upon open-source, vendor-agnostic software called the mass spectrometry query language (MassQL). MassQL, implemented in MassQLab, provides freedom for researchers to choose their analyte/s, mass spectrometry system (including liquid chromatography—mass spectrometry), and metrics of performance.

Results

In this report, we describe the use of MassQLab, demonstrate the construction of the required MassQL query, common metrics of performance (i.e., extracted ion chromatograms), uncommon metrics (i.e., MS/MS product ion spectra), and discuss insights gained about performance—including issues requiring correction prior to sample analysis.

Conclusions

MassQLab is a flexible solution for system suitability testing for mass spectrometry-based analytical measurements. Deficits in analytical performance, while unavoidable and rare, were noted prior to data collection and corrected. The open-source and adaptable nature of MassQLab will empower researchers and lead to improved implementation of system suitability testing.

原理：可重复分析仪器系统的性能对质谱分析至关重要，尤其是代谢组学，被恰当地命名为系统适用性测试。我们根据文献报告确定了需求，这些报告指出只有2%的论文执行了系统适用性测试。我们报告了MassQLab，它建立在开源的、与供应商无关的软件上，称为质谱查询语言（MassQL）。MassQL在MassQLab中实现，为研究人员提供了选择分析物/s、质谱系统（包括液相色谱-质谱）和性能指标的自由。在本报告中，我们描述了MassQLab的使用，演示了所需MassQL查询的构建，常见的性能指标（即提取的离子色谱图），不常见的指标（即MS/MS产物离子谱），并讨论了关于性能的见解，包括在样品分析之前需要纠正的问题。结论MassQLab是一个灵活的解决方案，用于基于质谱的分析测量的系统适用性测试。分析性能的缺陷，虽然是不可避免的和罕见的，但在数据收集和纠正之前被注意到。MassQLab的开源和适应性将赋予研究人员更多的权力，并改进系统适用性测试的实现。

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