Rapid Communications in Mass Spectrometry最新文献

Investigation of the mechanism of [M–H]+ ion formation in photoionized N-alkyl-substituted thieno[3,4-c]-pyrrole-4,6-dione derivatives during higher order MSn high-resolution mass spectrometry 在高阶 MSn 高分辨率质谱分析过程中研究光离子化 N-烷基取代的噻吩并[3,4-c]吡咯-4,6-二酮衍生物中[M-H]+ 离子的形成机制。

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-11-13 DOI: 10.1002/rcm.9940

Salim Sioud, Maan Amad, Zhiyong Zhu, Denis Lesage, Héloïse Dossmann

Rationale

The mechanism underlying dopant-assisted atmospheric pressure photoionization's (APPI) formation of ions is unclear and still under debate for many chemical classes. In this study, we reexamined the gas-phase reaction mechanisms responsible for the generation of [M–H]⁺ precursor ions, resulting from the loss of a single hydrogen atom, in a series of N-alkyl-substituted thieno[3,4-c]-pyrrole-4,6-dione (TPD) derivatives.

Methods

Atmospheric pressure photoionization combined with higher order MS/MSⁿ using high-resolution mass spectrometry (APPI-HR-CID-MSⁿ) and electronic structure calculations using density functional theory were used to determine the chemical structure of observed [M–H]⁺ ions.

Results

As a result, the higher order MSⁿ (n = 3) experiments revealed a reversed Diels–Alder fragmentation mechanism, leading to a common fragment ion at m/z 322 from the studied [M_1–5–H]⁺ ion species. In addition, the calculation for two chemical structure models (N-alkyl-TPD1 and N-alkyl-TPD5) showed that the fragment structure, resulting from the removal of the hydrogen atom connected to the third carbon atom of the N-alkyl side chain, has a more stable cyclic form compared with the linear one.

Conclusions

The proposed chemical structure of the N-alkyl TPD ion species, following the loss of a single hydrogen atom, was revealed during APPI-HR-CID-MSⁿ (n = 3) experiments on the [M–H]⁺ species. Hydrogen radical (H^•) abstraction from the alkyl side chain (e.g., hexyl, heptyl, octyl, 2-ethylhexyl, and nonyl) triggered a rearrangement in the radical cation structure of the N-alkyl-TPD derivatives, initiating cyclization and forming a six-membered ring that connects the oxygen atom to the third carbon atom in the alkyl chain. In addition, theoretical calculations supported the APPI-HR-CID-MSⁿ (n = 3) experiments by demonstrating that the proposed chemical structure, resulting from the intramolecular cyclization of the N-alkyl-TPD ion species, was stable in the presence of chlorobenzene. These findings will aid the structural determination and elucidation of molecules with similar core structures.

理由：掺杂剂辅助常压光离子化（APPI）形成离子的机理尚不清楚，对许多化学类别仍有争议。在本研究中，我们重新研究了一系列 N-烷基取代的噻吩并[3,4-c]-吡咯-4,6-二酮（TPD）衍生物在失去单个氢原子后产生[M-H]+前体离子的气相反应机制：方法：常压光离子化结合高分辨质谱（APPI-HR-CID-MSn）的高阶 MS/MSn，并利用密度泛函理论进行电子结构计算，以确定观察到的[M-H]+离子的化学结构：结果：高阶 MSn（n = 3）实验揭示了一种反向 Diels-Alder 破碎机制，导致所研究的[M1-5-H]+ 离子物种在 m/z 322 处产生一个共同的碎片离子。此外，两种化学结构模型（N-烷基-TPD1 和 N-烷基-TPD5）的计算表明，与线性结构相比，去除与 N-烷基侧链第三个碳原子相连的氢原子后产生的碎片结构具有更稳定的环状形式：结论：APPI-HR-CID-MSn（n = 3）实验揭示了 N-烷基 TPD 离子在失去单个氢原子后的化学结构。从烷基侧链（如己基、庚基、辛基、2-乙基己基和壬基）中抽取氢自由基（H-）会引发 N-烷基-TPD 衍生物自由基阳离子结构的重排，从而启动环化作用并形成一个六元环，将氧原子与烷基链中的第三个碳原子连接起来。此外，理论计算支持 APPI-HR-CID-MSn（n = 3）实验，证明 N-烷基-TPD 离子物种分子内环化产生的拟议化学结构在氯苯存在下是稳定的。这些发现将有助于对具有类似核心结构的分子进行结构测定和阐明。

{"title":"Investigation of the mechanism of [M–H]+ ion formation in photoionized N-alkyl-substituted thieno[3,4-c]-pyrrole-4,6-dione derivatives during higher order MSn high-resolution mass spectrometry","authors":"Salim Sioud, Maan Amad, Zhiyong Zhu, Denis Lesage, Héloïse Dossmann","doi":"10.1002/rcm.9940","DOIUrl":"10.1002/rcm.9940","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>The mechanism underlying dopant-assisted atmospheric pressure photoionization's (APPI) formation of ions is unclear and still under debate for many chemical classes. In this study, we reexamined the gas-phase reaction mechanisms responsible for the generation of [M–H]<sup>+</sup> precursor ions, resulting from the loss of a single hydrogen atom, in a series of <i>N</i>-alkyl-substituted thieno[3,4-<i>c</i>]-pyrrole-4,6-dione (TPD) derivatives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Atmospheric pressure photoionization combined with higher order MS/MS<sup><i>n</i></sup> using high-resolution mass spectrometry (APPI-HR-CID-MS<sup><i>n</i></sup>) and electronic structure calculations using density functional theory were used to determine the chemical structure of observed [M–H]<sup>+</sup> ions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As a result, the higher order MS<sup><i>n</i></sup> (<i>n</i> = 3) experiments revealed a reversed Diels–Alder fragmentation mechanism, leading to a common fragment ion at <i>m</i>/<i>z</i> 322 from the studied [M<sub>1–5</sub>–H]<sup>+</sup> ion species. In addition, the calculation for two chemical structure models (<i>N</i>-alkyl-TPD1 and <i>N</i>-alkyl-TPD5) showed that the fragment structure, resulting from the removal of the hydrogen atom connected to the third carbon atom of the <i>N</i>-alkyl side chain, has a more stable cyclic form compared with the linear one.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The proposed chemical structure of the <i>N</i>-alkyl TPD ion species, following the loss of a single hydrogen atom, was revealed during APPI-HR-CID-MS<sup><i>n</i></sup> (<i>n</i> = 3) experiments on the [M–H]<sup>+</sup> species. Hydrogen radical (H<sup>•</sup>) abstraction from the alkyl side chain (e.g., hexyl, heptyl, octyl, 2-ethylhexyl, and nonyl) triggered a rearrangement in the radical cation structure of the <i>N</i>-alkyl-TPD derivatives, initiating cyclization and forming a six-membered ring that connects the oxygen atom to the third carbon atom in the alkyl chain. In addition, theoretical calculations supported the APPI-HR-CID-MS<sup><i>n</i></sup> (<i>n</i> = 3) experiments by demonstrating that the proposed chemical structure, resulting from the intramolecular cyclization of the <i>N</i>-alkyl-TPD ion species, was stable in the presence of chlorobenzene. These findings will aid the structural determination and elucidation of molecules with similar core structures.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"39 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and validation of a rapid HPLC-MS/MS method for simultaneous determination of cyclosporine A and tacrolimus in whole blood for routine therapeutic drug monitoring in organ transplantation 开发并验证一种快速 HPLC-MS/MS 方法，用于同时测定全血中的环孢素 A 和他克莫司，以监测器官移植中的常规治疗药物。

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-11-12 DOI: 10.1002/rcm.9932

Fei-fei Han, Hong-chuan Liu, Ting Hu, Peng-fei Li, Rui Zhao, Zhuo-ling An

Background

Therapeutic drug monitoring is an integral part of organ transplantation. A rapid, simple, economical, and robust high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining the immunosuppressants cyclosporine A and tacrolimus might increase detection efficiency.

Methods

In this study, we developed and validated a rapid HPLC-MS/MS method. Whole blood samples of 100 μL were prepared by protein precipitation with acetonitrile and 0.5 mol. L⁻¹ ZnSO₄. Chromatography was performed on a pre-column using a gradient elution with 20 mmol. L⁻¹ ammonium formate and 0.1% (v/v) formic acid in water (mobile phase A) and 0.1% (v/v) formic acid in methanol (mobile phase B) at a flow rate of 1.5 mL.min⁻¹. The analysis time was 2.2 min. Electrospray ionization and multiple reaction monitoring were performed. The lower limit of quantification was set at 1 ng. L⁻¹ for tacrolimus and 50 ng. L⁻¹ for cyclosporine A.

Results

The method showed adequate accuracy and precision with a sufficient linear range. The calibration curve range of tacrolimus and cyclosporine A was 1–30 and 50–1500 ng·mL-¹, respectively. All correlation coefficients were >0.99.

Conclusions

The developed HPLC-MS/MS is rapid and can be used for simultaneous monitoring of tacrolimus and cyclosporine A.

背景：治疗药物监测是器官移植不可或缺的一部分。一种快速、简单、经济、稳健的高效液相色谱-串联质谱（HPLC-MS/MS）方法可同时测定免疫抑制剂环孢素 A 和他克莫司，从而提高检测效率：本研究开发并验证了一种快速 HPLC-MS/MS 方法。全血样品 100 μL 用乙腈和 0.5 mol.L-1 ZnSO4沉淀蛋白质。在预柱上用 20 mmol.L-1 甲酸铵和 0.1% (v/v) 甲酸水（流动相 A）以及 0.1% (v/v) 甲酸甲醇（流动相 B）进行梯度洗脱，流速为 1.5 mL.min-1。分析时间为 2.2 分钟。进行了电喷雾离子化和多反应监测。他克莫司的定量下限为 1 纳克/升-1。L-1，环孢素 A 为 50 ng。L-1：该方法准确度和精密度良好，线性范围足够宽。他克莫司和环孢素 A 的校准曲线范围分别为 1-30 和 50-1500 ng-mL-1。所有相关系数均大于 0.99：所开发的高效液相色谱-质谱/串联质谱法速度快，可用于他克莫司和环孢素 A 的同时监测。

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引用次数: 0

A fragmentation study of disaccharide flavonoid C-glycosides using triple quadrupole mass spectrometry and its application for identification of flavonoid C-glycosides in Odontosoria chinensis 利用三重四极杆质谱对双糖黄酮 C-糖苷的片段研究及其在鉴定小柴胡中黄酮 C-糖苷中的应用。

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-11-09 DOI: 10.1002/rcm.9936

Bin Huang, Fangjun Chen, Xiang Zhang, Yanzhen Hu, Yuanyuan Zhang, Le Chen, Yan Meng, Ping Wen

Rationale

Flavonoid C-glycosides have a wide range of pharmacological activities. However, there are few mass spectrometric research on C,O-disaccharide flavonoid C-glycosides and di-C,O-saccharide flavonoid C-glycosides. Their low-energy collision-induced dissociation (ESI-CID-MS/MS) fragmentation pattern and differences have not been reported, and the fragment ion library is incomplete. Therefore, it was essential to elucidate the fragmentation patterns of disaccharide flavonoid C-glycosides, which is described in this study.

Methods

Four disaccharide flavonoid C-glycosides such as vitexin-4″-O-glucoside were analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometer (UPLC-MS/MS) using electrospray ionization (ESI) in both positive and negative ion modes. Each ion and its proposed fragmentation pathways of the four disaccharide flavonoid C-glycosides were analyzed comprehensively. Finally, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and the established fragmentation patterns have been used to identify disaccharide flavonoid C-glycosides in Odontosoria Chinensis.

Results

The fragmentation pathways of C,O-disaccharide flavonoid C-glycosides and di-C,O-saccharide flavonoid C-glycosides are similar. They both have the mass spectrometric characteristics of O-glycoside and C-glycoside. Product ions after mixed pathways of neutral fragments such as saccharide ring fragment, O-glycosides, H₂O, and CH₂O elimination appeared in both types of flavonoid C-glycosides, but their relative abundances are significantly different. According to the established fragmentation patterns, di-C,O-saccharide flavonoid glycosides were also found in Odontosoria chinensis.

Conclusion

The fragment ions at m/z 431, 413, 341, 311, 293, and 282 in negative ion mode and m/z 293, 282, 577, 559, 541, 523, 529, and 499 in positive ion mode can serves as the main characteristics for identifying C,O-disaccharide flavonoid C-glycosides and di-C,O-saccharide flavonoid C-glycosides.

理由黄酮 C-糖苷具有广泛的药理活性。然而，有关 C,O-二糖黄酮 C-苷和二 C,O-二糖黄酮 C-苷的质谱研究却很少。它们的低能碰撞诱导解离（ESI-CID-MS/MS）碎片模式和差异尚未见报道，碎片离子库也不完整。因此，阐明双糖黄酮 C-糖苷的碎片模式至关重要，本研究对此进行了描述：方法：采用超高效液相色谱-三重四极杆串联质谱仪（UPLC-MS/MS），以正、负离子模式电喷雾离子化（ESI）分析了牡荆素-4″-O-葡萄糖苷等四种双糖黄酮 C-糖苷。对四种双糖黄酮 C-糖苷的每个离子及其碎片路径进行了全面分析。最后，利用超高效液相色谱-四极杆飞行时间质谱法（UPLC-Q-TOF-MS/MS）和已建立的碎片模式鉴定了麦冬中的双糖黄酮 C-糖苷：结果：C,O-二糖黄酮C-糖苷和二糖黄酮C-糖苷的破碎途径相似。它们都具有 O-糖苷和 C-糖苷的质谱特征。两类黄酮 C-糖苷中都出现了糖环片段、O-糖苷、H2O 和 CH2O 等中性片段混合消除后的产物离子，但其相对丰度有显著差异。根据已建立的碎片模式，在小龙蔘中还发现了二-C,O-糖黄酮苷：结论：在负离子模式下，m/z 431、413、341、311、293和282的碎片离子；在正离子模式下，m/z 293、282、577、559、541、523、529和499的碎片离子是鉴定C,O-二糖黄酮C-糖苷和二-C,O-糖黄酮C-糖苷的主要特征。

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引用次数: 0

The environmental and health protection commitments of Jean-François Muller: Academic and societal endeavor. 让-弗朗索瓦-穆勒的环境和健康保护承诺：学术和社会努力。

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-11-09 DOI: 10.1002/rcm.9938

Jean-François Gal, Pierre-Charles Maria

引用次数: 0

Two Erigeron species comparison based on their ingredient profile by UPLC-PDA-QTOF-MS/MS and discriminant analysis 通过 UPLC-PDA-QTOF-MS/MS 和判别分析，比较两种麦角菌的成分特征。

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-11-04 DOI: 10.1002/rcm.9929

Jianguang Zhang, Yue Wang, Jiansang Wulu, Wenfang Jin, Qing Yang, Zhifeng Zhang

Rationale

Erigeron breviscapus (EB) and Erigeron multiradiatus (EM) are the two species of the genus Erigeron (Asteraceae) with extremely close genetic relationships. They were used as the same “meiduoluomi” for the treatment of plague and epidemics in traditional Tibetan medicine. But in traditional Chinese medicine, only EB is used for treatment of cerebrovascular obstruction, hemiplegia due to stroke, coronary artery obstruction, chest congestion, and angina pectoris. These two Erigeron species show different effects in different traditional medicine systems. Therefore, analyzing the chemical compositions of two species will not only enhance comprehension of their medicinal properties but also foster the advancement and exploration of novel applications. However, to date, there has been no comprehensive and detailed investigation comparing the constituents of EB and EM.

Methods

A methodology for rapid identification of chemical profiles from two Erigeron species was devised through the integration of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) and multivariate statistical analysis. Additionally, a UHPLC-photo-diode array (PDA) method was established to precisely quantify of 11 components.

Results

A total of 58 constituents comprising flavonoids, phenolic acids, saponin, and long chain fatty acids were elucidated. Thirteen compounds were identified as potential differentiators in chemical profiles among the two Erigeron species. For quantitative assessment, 11 bioactive compounds were simultaneously quantified across 49 batches of Erigeron species samples utilizing UHPLC-PDA with wavelengths of 325, 254, and 266 nm. The method demonstrated excellent precision, linearity, accuracy, repeatability, stability, and recovery.

Conclusions

The findings from this study will serve as a reference for quality control, functional activity exploration, and improved clinical application based on the ingredient profiles of the two species. Furthermore, this inaugural investigation into the ingredient profiles of these two species will enhance the potential and optimal utilization of both EB and EM resources.

理由：Erigeron breviscapus（EB）和 Erigeron multiradiatus（EM）是菊科 Erigeron 属的两个物种，它们之间的遗传关系极为密切。在传统藏医药中，它们被作为同一种 "meiduoluomi "用于治疗瘟疫和流行病。但在传统中药中，只有乙贝用于治疗脑血管阻塞、中风偏瘫、冠状动脉阻塞、胸闷和心绞痛。这两种麦冬在不同的传统医学体系中表现出不同的功效。因此，分析这两个物种的化学成分不仅能加深对其药用特性的理解，还能促进新应用的开发和探索。然而，迄今为止，还没有对 EB 和 EM 的成分进行全面而详细的调查比较：方法：通过整合超高效液相色谱-四极杆飞行时间串联质谱（UHPLC-QTOF-MS/MS）和多元统计分析，设计了一种快速鉴定两种艾草化学成分的方法。此外，还建立了超高效液相色谱-光电二极管阵列（PDA）方法，对 11 种成分进行精确定量：结果：共发现 58 种成分，包括黄酮类、酚酸、皂苷和长链脂肪酸。其中有 13 种化合物被确定为两种麦冬草化学成分的潜在差异成分。在定量评估方面，利用波长为 325、254 和 266 nm 的超高效液相色谱-PDA，同时对 49 个批次的麦冬样品中的 11 种生物活性化合物进行了定量分析。该方法在精密度、线性、准确度、重复性、稳定性和回收率方面均表现优异：本研究的结果将为质量控制、功能活性探索和根据两种植物的成分特征改进临床应用提供参考。此外，对这两种植物成分的首次调查将提高 EB 和 EM 资源的潜力和最佳利用率。

{"title":"Two Erigeron species comparison based on their ingredient profile by UPLC-PDA-QTOF-MS/MS and discriminant analysis","authors":"Jianguang Zhang, Yue Wang, Jiansang Wulu, Wenfang Jin, Qing Yang, Zhifeng Zhang","doi":"10.1002/rcm.9929","DOIUrl":"10.1002/rcm.9929","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p><i>Erigeron breviscapus</i> (EB) and <i>Erigeron multiradiatus</i> (EM) are the two species of the genus <i>Erigeron</i> (Asteraceae) with extremely close genetic relationships. They were used as the same “meiduoluomi” for the treatment of plague and epidemics in traditional Tibetan medicine. But in traditional Chinese medicine, only EB is used for treatment of cerebrovascular obstruction, hemiplegia due to stroke, coronary artery obstruction, chest congestion, and angina pectoris. These two <i>Erigeron</i> species show different effects in different traditional medicine systems. Therefore, analyzing the chemical compositions of two species will not only enhance comprehension of their medicinal properties but also foster the advancement and exploration of novel applications. However, to date, there has been no comprehensive and detailed investigation comparing the constituents of EB and EM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A methodology for rapid identification of chemical profiles from two <i>Erigeron</i> species was devised through the integration of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) and multivariate statistical analysis. Additionally, a UHPLC-photo-diode array (PDA) method was established to precisely quantify of 11 components.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 58 constituents comprising flavonoids, phenolic acids, saponin, and long chain fatty acids were elucidated. Thirteen compounds were identified as potential differentiators in chemical profiles among the two <i>Erigeron</i> species. For quantitative assessment, 11 bioactive compounds were simultaneously quantified across 49 batches of <i>Erigeron</i> species samples utilizing UHPLC-PDA with wavelengths of 325, 254, and 266 nm. The method demonstrated excellent precision, linearity, accuracy, repeatability, stability, and recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings from this study will serve as a reference for quality control, functional activity exploration, and improved clinical application based on the ingredient profiles of the two species. Furthermore, this inaugural investigation into the ingredient profiles of these two species will enhance the potential and optimal utilization of both EB and EM resources.</p>\u0000 </section>\u0000 </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":"39 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimization of protein identifications through the use of different chromatographic approaches and bioinformatic pipelines 通过使用不同的色谱方法和生物信息学管道优化蛋白质鉴定。

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-11-04 DOI: 10.1002/rcm.9937

Jesus D. Castaño, Francis Beaudry

Rationale

Selection of proteomic workflows for a given project can be a daunting task. This research provides a guide outlining the impact on protein identification of different steps such as chromatographic separation, data acquisition strategies, and bioinformatic pipelines. The data presented here will help experts and nonexpert proteomic users to increase proteome coverage and peptide identification.

Methods

HeLa protein digests were analyzed through different C18 chromatographic columns (15 and 50 cm in length), using top 12 data-dependent acquisition (DDA), top 20 DDA, and data-independent acquisition (DIA) with a nanospray source in positive mode in a Thermo Q Exactive instrument. The raw data were analyzed using different search engines, rescoring approaches, and multi-engine searches. The results were analyzed in the context of peptide and protein identifications, precursor properties, and computation requirements to understand the differences between methods.

Results

Our results showed that higher column lengths and top N DDA approaches were able to significantly increase protein identifications. The use of multiple search engines yielded limited gains, whereas the use of rescoring methods clearly outperformed other strategies. Finally, DIA approaches, although successful at generating new identifications, had a limited performance influenced by the previous collection of DDA data, which could prohibitively increase instrument time. Nonetheless, the use of library-free methods showed promising results.

Conclusions

Our results highlight the impact of different experimental approaches on proteome coverage. Changes in chromatographic columns, data acquisition, or bioinformatic analysis can significantly increase the number of protein identifications (>400%). Thus, this research provides a reference upon which to build a successful proteomic workflow with different considerations at every step.

理由：为特定项目选择蛋白质组工作流程是一项艰巨的任务。本研究提供了一份指南，概述了色谱分离、数据采集策略和生物信息管道等不同步骤对蛋白质鉴定的影响。方法：通过不同的 C18 色谱柱（长度分别为 15 厘米和 50 厘米），在 Thermo Q Exactive 仪器的正向模式下使用前 12 位数据依赖性采集（DDA）、前 20 位数据依赖性采集（DDA）和纳米喷雾源数据无关性采集（DIA），对 HeLa 蛋白消化液进行分析。使用不同的搜索引擎、重新评分方法和多引擎搜索对原始数据进行了分析。我们结合肽和蛋白质鉴定、前体特性和计算要求对结果进行了分析，以了解不同方法之间的差异：结果：我们的研究结果表明，较高的柱长和前 N DDA 方法能够显著提高蛋白质鉴定率。使用多个搜索引擎的收益有限，而使用重评分方法的效果明显优于其他策略。最后，DIA 方法虽然能成功地产生新的鉴定结果，但其性能受到之前 DDA 数据收集的影响，可能会过多地增加仪器时间。尽管如此，无库方法的使用还是取得了可喜的成果：我们的研究结果凸显了不同实验方法对蛋白质组覆盖率的影响。色谱柱、数据采集或生物信息分析的改变可显著增加蛋白质鉴定的数量（>400%）。因此，这项研究为建立成功的蛋白质组工作流程提供了参考，每一步都有不同的考虑因素。

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引用次数: 0

Triple-oxygen isotopes of stony micrometeorites by secondary ion mass spectrometry (SIMS): Olivine, basaltic glass and iron oxide matrix effects for sensitive high-mass resolution ion microprobe-stable isotope (SHRIMP-SI) 利用二次离子质谱（SIMS）分析石质微陨石的三氧同位素：橄榄石、玄武岩玻璃和氧化铁基质对灵敏度高、质量分辨率高的离子微探针-稳定同位素（SHRIMP-SI）的影响。

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-10-30 DOI: 10.1002/rcm.9921

Seann J. McKibbin, Janaína N. Ávila, Trevor R. Ireland, Matthias Van Ginneken, Bastien Soens, Flore Van Maldeghem, Matthew Huber, Leonardo Baeza, Aditya Patkar, Frank Vanhaecke, Vinciane Debaille, Philippe Claeys, Steven Goderis

Rationale

Micrometeorites are extraterrestrial particles smaller than ~2 mm in diameter, most of which melted during atmospheric entry and crystallised or quenched to form ‘cosmic spherules’. Their parentage among meteorite groups can be inferred from triple-oxygen isotope compositions, for example, by secondary ion mass spectrometry (SIMS). This method uses sample efficiently, preserving spherules for other investigations. While SIMS precisions are improving steadily, application requires assumptions about instrumental mass fractionation, which is controlled by sample chemistry and mineralogy (matrix effects).

Methods

We have developed a generic SIMS method using sensitive high-mass resolution ion micro probe-stable isotope (SHRIMP-SI) that can be applied to finely crystalline igneous textures as in cosmic spherules. We correct for oxygen isotope matrix effects using the bulk chemistry of samples obtained by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and model bulk chemical compositions as three-component mixtures of olivine, basaltic glass and Fe-oxide (magnetite), finding a unique matrix correction for each target.

Results

Our first results for cosmic spherules from East Antarctica compare favourably with established micrometeorite groups defined by precise and accurate but consumptive bulk oxygen isotope methods. The Fe-oxide content of each spherule is the main control on magnitude of oxygen isotope ratio bias, with effects on δ¹⁸O up to ~6‰. Our main peak in compositions closely coincides with so-called ‘Group 1’ objects identified by consumptive methods.

Conclusions

The magnitude of SIMS matrix effects we find is similar to the previous intraspherule variations, which are now the limiting factor in understanding their compositions. The matrix effect for each spherule should be assessed quantitatively and individually, especially addressing Fe-oxide content. We expect micrometeorite triple-oxygen isotope compositions obtained by SIMS to converge on the main clusters (Groups 1 to 4) after correction firstly for magnetite content and secondarily for other phases (e.g., basaltic glass) in each target.

理由：微陨石是直径小于 ~2 毫米的地外粒子，其中大部分在进入大气层时熔化，结晶或淬火形成 "宇宙球粒"。通过二次离子质谱法（SIMS）等方法，可以从三氧同位素组成推断出它们在陨石群中的母体。这种方法能有效地利用样本，为其他研究保留球粒。虽然 SIMS 的精确度在稳步提高，但其应用需要对仪器质量分馏进行假设，而仪器质量分馏受样品化学和矿物学（基质效应）的控制：方法：我们利用灵敏的高质分辨率离子微探针-稳定同位素（SHRIMP-SI）开发了一种通用的 SIMS 方法，可用于细晶火成岩质地，如宇宙球粒。我们利用激光烧蚀电感耦合等离子体质谱法（LA-ICP-MS）获得的样品块体化学成分来校正氧同位素基质效应，并将块体化学成分建模为橄榄石、玄武岩玻璃和氧化铁（磁铁矿）的三组分混合物，为每个目标找到了独特的基质校正方法：我们对南极洲东部宇宙球粒的首次研究结果与通过精确、准确但消耗性大的氧同位素方法确定的微陨石群相比毫不逊色。每个球粒的氧化铁含量是控制氧同位素比值偏差大小的主要因素，对 δ18O 的影响可达 ~6‰。我们的主要成分峰值与消耗性方法确定的所谓 "第 1 组 "天体非常吻合：我们发现的SIMS基质效应的大小与之前的球内变化相似，而球内变化是目前了解其成分的限制因素。每个球粒的基质效应都应单独进行定量评估，尤其是针对氧化铁的含量。我们预计通过 SIMS 获得的微陨石三氧同位素成分，在首先对磁铁矿含量进行校正，其次对每个目标中的其他相（如玄武岩玻璃）进行校正之后，将趋同于主要群（第 1 至第 4 组）。

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引用次数: 0

Identification and characterization of alkaline hydrolytic degradation products of ivacaftor by UPLC-PDA and UPLC-ESI-QTOF-MS techniques 利用 UPLC-PDA 和 UPLC-ESI-QTOF-MS 技术鉴定和表征伊伐卡夫多的碱性水解降解产物。

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-10-30 DOI: 10.1002/rcm.9930

Aastha Bishnoi, Alka Bali, Akshay Kumar

Rationale

The study of inherent stability characteristics of drugs has been advocated to be important by various regulatory agencies like the ICH, USFDA, and others. The current work was envisaged to investigate the forced degradation profile of the drug ivacaftor under ICH-prescribed stress conditions, identification of its potential degradants, and postulation of the degradation routes for their generation.

Methods

The stress degradation studies were performed on the drug as per the ICH guideline Q1A(R2). A UPLC-photodiode array-based chromatographic method was developed to satisfactorily resolve the drug from its degradation products, validated in accordance with various ICH prescribed parameters, and assessed for its BAGI practicality index. The degradation products were identified and characterized by UPLC-ESI-QTOF-MS studies.

Results

The drug was found to significantly degrade under conditions of alkaline hydrolytic stress and it was found to be stable under all other stressor environments including acid/neutral hydrolytic, photolytic, thermal, and oxidative stress. Four alkaline hydrolytic degradation products (I-IV) were revealed by UPLC-QTOF-MS studies which were well-resolved from the drug over a C18 UPLC column by the developed UPLC-PDA method. The detection wavelength was selected as 310 nm. Characterization of the four degradation products (I–IV) was carried out by their mass spectral data and their respective degradation routes were elucidated.

Conclusions

A UPLC-PDA method was developed and validated for ivacaftor and its practicality BAGI index was computed. Four alkaline hydrolytic degradation products of ivacaftor were revealed through UPLC-ESI-QTOF-MS studies and corresponding degradation routes were elucidated.

理由：ICH、USFDA 等多个监管机构都认为对药物内在稳定性特征的研究非常重要。目前的工作旨在研究药物 ivacaftor 在 ICH 规定的应力条件下的强制降解概况，确定其潜在降解物，并推测其产生的降解途径：方法：根据 ICH 指南 Q1A(R2)，对药物进行应力降解研究。开发了一种基于超高效液相色谱-光电二极管阵列的色谱法，可从降解产物中分辨出令人满意的药物，并根据 ICH 规定的各种参数进行了验证，还评估了其 BAGI 实用性指数。通过 UPLC-ESI-QTOF-MS 研究对降解产物进行了鉴定和表征：结果：发现该药物在碱性水解应力条件下降解明显，而在所有其他应力环境下，包括酸性/中性水解、光解、热应力和氧化应力，该药物均保持稳定。通过 UPLC-QTOF-MS 研究发现了四种碱性水解降解产物（I-IV），采用所开发的 UPLC-PDA 方法，这些产物在 C18 UPLC 柱上能很好地从药物中分离出来。检测波长选为 310 nm。通过质谱数据对四种降解产物（I-IV）进行了表征，并阐明了它们各自的降解途径：建立并验证了伊伐卡夫多的UPLC-PDA方法，并计算了其实用性BAGI指数。通过UPLC-ESI-QTOF-MS研究发现了伊伐卡夫多的四种碱性水解降解产物，并阐明了相应的降解途径。

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引用次数: 0

How do cocaine and morphine in methanol solution desorb at the last moment of Leidenfrost phenomenon-assisted thermal desorption? 甲醇溶液中的可卡因和吗啡如何在莱顿弗罗斯特现象辅助热脱附的最后时刻脱附？

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-10-30 DOI: 10.1002/rcm.9933

Kenzo Hiraoka, Stephanie Rankin-Turner, Dilshadbek T. Usmanov, Sherzod M. Akhmedov, Satoshi Ninomiya

Rationale

The objective of the present study is to investigate desorption of low-volatility analytes in Leidenfrost phenomenon-assisted thermal desorption (LPTD).

Methods

LPTD was investigated for 5 μL solutions of 0.03 ppm cocaine or morphine in methanol (sample weight: 0.12 ng) by using heated metal surfaces (240°C) polished by abrasives with grit numbers from #5000 (~3 μm) to #100 (~200 μm).

Results

The analyte signals were detected only after the complete evaporation of methanol solvent and the formed analyte residues levitated on the heater surface. The strongest ion signals were obtained with grit number #100.

Conclusions

Because the analyte residue does not come into contact with the heated surface but levitates on the hot substrate after the evaporation of the solvent, thermal decomposition of the analyte is largely suppressed. This is a great merit of LPTD for trace analysis of low-volatility and thermally labile compounds.

理由：本研究的目的是调查低挥发性分析物在莱顿弗罗斯特现象辅助热脱附（LPTD）中的脱附情况：方法：采用加热的金属表面（240°C），用粒度从 #5000（约 3 μm）到 #100（约 200 μm）的磨料抛光，对甲醇中 0.03 ppm 可卡因或吗啡的 5 μL 溶液（样品重量：0.12 ng）进行莱顿弗罗斯特现象辅助热脱附研究：只有在甲醇溶剂完全蒸发后才能检测到分析物信号，形成的分析物残留物悬浮在加热器表面。结论：由于被分析物残留物不会从加热器表面脱落，因此不会产生强烈的离子信号：由于溶剂蒸发后分析物残留物并不与加热表面接触，而是悬浮在热基底上，因此分析物的热分解在很大程度上被抑制了。这是 LPTD 用于低挥发性和热敏性化合物痕量分析的一大优点。

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引用次数: 0

A novel analytical strategy based on gas chromatography-Orbitrap high-resolution mass spectrometry combined with solid-phase extraction for the monitoring of stanozolol misuse in human urine 一种基于气相色谱-轨道阱高分辨质谱法并结合固相萃取的新型分析策略，用于监测人体尿液中滥用司坦唑醇的情况。

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry

Pub Date : 2024-10-30 DOI: 10.1002/rcm.9935

Siying Zheng, Ziyi Ji, Yuqi Ge, Xian Fang, Mengpan Liu, Haoyi Sun, Xiaojun Deng, Lei Liao

Rationale

Stanozolol, an anabolic androgenic steroid listed in Part S1 of the World Anti-Doping Agency Prohibited List, exhibits a low response and significant matrix interference in urine samples when using liquid–liquid extraction–gas chromatography–mass spectrometry (GC–MS). Enhancing sample preparation techniques remains essential for the effective detection of stanozolol and its metabolites.

Methods

A method for determining stanozolol and its metabolites (3′-OH-stanozolol, 4β-OH-stanozolol, and 16β-OH-stanozolol) in human urine was developed and validated using GC-Orbitrap high-resolution MS combined with optimized mixed-mode solid-phase extraction (SPE). This method was applied to urine samples from two volunteers who orally administered a single dose of stanozolol, with samples collected over a 30-day period post-administration.

Results

The optimized mixed-mode SPE method reduced matrix interference and achieved satisfactory extraction efficiency and high sensitivity, enabling confident identification of all targets in human urine. Validation showed extraction recovery of 74% to 81% and limits of detection from 0.1 to 0.25 ng mL⁻¹. The method was successfully applied to detect urinary excretion profiles of stanozolol and its metabolites in positive volunteer samples.

Conclusion

This study presents a novel detection protocol for stanozolol and its metabolites, enhancing the monitoring of stanozolol abuse and contributing to the integrity of sports competitions. This protocol offers a robust tool for anti-doping laboratories, aiding in the accurate detection of stanozolol misuse and supporting the enforcement of fair play in athletics.

理由：司坦唑醇是一种同化雄性类固醇，已被列入世界反兴奋剂机构禁用清单 S1 部分，在使用液液萃取-气相色谱-质谱联用技术（GC-MS）检测尿样时，司坦唑醇的响应度较低，且存在明显的基质干扰。加强样品制备技术对于有效检测司坦唑醇及其代谢物仍然至关重要：方法：采用GC-Orbitrap高分辨率质谱结合优化的混合模式固相萃取（SPE）技术，开发并验证了测定人体尿液中丹诺唑醇及其代谢物（3'-OH-丹诺唑醇、4β-OH-丹诺唑醇和16β-OH-丹诺唑醇）的方法。该方法适用于两名口服单剂量司坦唑醇的志愿者的尿样，并在用药后 30 天内采集尿样：结果：优化的混合模式固相萃取方法减少了基质干扰，萃取效率令人满意，灵敏度高，能够可靠地鉴定人体尿液中的所有目标物。验证表明萃取回收率为 74% 至 81%，检出限为 0.1 至 0.25 纳克 mL-1。该方法被成功应用于检测阳性志愿者样本中丹诺唑醇及其代谢物的尿液排泄曲线：本研究提出了一种新型的司坦唑醇及其代谢物检测方案，可加强对滥用司坦唑醇行为的监测，促进体育比赛的公正性。该方案为反兴奋剂实验室提供了一个强大的工具，有助于准确检测滥用司坦唑醇的情况，并支持田径运动中公平竞赛的实施。

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引用次数: 0