Pub Date : 2025-02-05Epub Date: 2025-01-04DOI: 10.1021/jasms.4c00490
Nathan W Buzitis, Brian H Clowers
Phased structures for lossless ion manipulation offer significant improvements over the scanning second gate method for coupling with ion trap mass analyzers. With an experimental run time of under 1 min for select conditions and an average run time of less than 4 min, this approach significantly reduces experimental time while enhancing the temporal duty cycle. The outlined SLIM system connects to an ion trap mass analyzer via a PCB stacked ring ion guide, which replaces the commercial ion optics and capillary inlet. By applying a discrete and repeating injection pulse and solving a series of algebraic equations, the system reconstructs an arrival time distribution with a minimal degree of error with enhanced ion throughput. To demonstrate the feasibility of this approach, the 3.4-m SLIM system resolves gas-phase conformers for various small peptides and proteins. This system and methodology also enable direct implementation between SLIM and ion trap mass analyzers traditionally interfaced with front separation systems such as liquid chromatography.
相控结构无损离子操作提供了显著改进扫描第二门方法耦合离子阱质量分析仪。在特定条件下,实验运行时间小于1分钟,平均运行时间小于4分钟,这种方法显著减少了实验时间,同时提高了时间占空比。概述的SLIM系统通过PCB堆叠环形离子波导连接到离子阱质量分析仪,取代了商用离子光学器件和毛细管入口。通过施加一个离散和重复的注入脉冲并求解一系列代数方程,该系统以最小的误差程度重建了到达时间分布,并提高了离子通量。为了证明这种方法的可行性,3.4 m SLIM系统可以解析各种小肽和蛋白质的气相构象。该系统和方法还可以在SLIM和离子阱质量分析仪之间直接实施,传统上与前分离系统(如液相色谱)接口。
{"title":"Efficient Coupling of Structures for Lossless Ion Manipulations with Ion Trap Mass Analyzers Using Phase Modulation.","authors":"Nathan W Buzitis, Brian H Clowers","doi":"10.1021/jasms.4c00490","DOIUrl":"10.1021/jasms.4c00490","url":null,"abstract":"<p><p>Phased structures for lossless ion manipulation offer significant improvements over the scanning second gate method for coupling with ion trap mass analyzers. With an experimental run time of under 1 min for select conditions and an average run time of less than 4 min, this approach significantly reduces experimental time while enhancing the temporal duty cycle. The outlined SLIM system connects to an ion trap mass analyzer via a PCB stacked ring ion guide, which replaces the commercial ion optics and capillary inlet. By applying a discrete and repeating injection pulse and solving a series of algebraic equations, the system reconstructs an arrival time distribution with a minimal degree of error with enhanced ion throughput. To demonstrate the feasibility of this approach, the 3.4-m SLIM system resolves gas-phase conformers for various small peptides and proteins. This system and methodology also enable direct implementation between SLIM and ion trap mass analyzers traditionally interfaced with front separation systems such as liquid chromatography.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"424-432"},"PeriodicalIF":3.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05Epub Date: 2025-01-20DOI: 10.1021/jasms.4c00399
Mariachiara Bianco, Ilario Losito, Giovanni Ventura, Beniamino Leoni, Onofrio Davide Palmitessa, Massimiliano Renna, Pietro Santamaria, Cosima Damiana Calvano, Tommaso R I Cataldi
Coenzyme Q10 (CoQ10) and closely related compounds with varying isoprenoid tail lengths (CoQn, n = 6-9) are biochemical cofactors involved in many physiological processes, playing important roles in cellular respiration and energy production. Liquid chromatography (LC) coupled with single or tandem mass spectrometry (MS) using electrospray (ESI) or atmospheric pressure chemical ionization (APCI) is considered the gold standard for the identification and quantification of CoQ10 in food and biological samples. However, the characteristic fragmentation exhibited by the CoQ10 radical anion ([M]•-, m/z 862.684), the prevailing ion generated by APCI in negative polarity, has not been studied in detail. In this work, a systematic study was carried out to clarify this issue, using higher collisional energy dissociation (HCD) with high-resolution tandem FTMS and collision-induced dissociation-low-resolution sequential mass spectrometry (CID-MSn, n = 2-4). Various fragmentation pathways were successfully interpreted, with some structures proposed for product ions checked using density functional theory (DFT) calculations. Besides the already-known detachments of methyl radicals occurring directly from the CoQ10 radical anion and leading to ions like [M - CH3]- and [M - 2CH3]•-, the homolytic cleavage of C-C bonds along the oligo-isoprenoid side chain was tentatively proposed to explain some of the observed fragmentations. As a result, the generation of uncommon yet potentially stable distonic biradical anions was hypothesized, with some of them likely undergoing intramolecular cyclization to generate ions without unpaired electrons. Diagnostic product ions emerged from the fragmentation processes of CoQ10 and were found to be common also to the radical anions of other CoQn derivatives (n = 7-9), facilitating their identification in extracts of edible Brassicaceae plant microgreens by reversed-phase liquid chromatography (RPLC)-APCI-FTMS.
辅酶Q10 (CoQ10)及其密切相关的异戊二烯类尾长化合物(CoQn, n = 6-9)是参与许多生理过程的生化辅助因子,在细胞呼吸和能量产生中起重要作用。液相色谱(LC)与电喷雾(ESI)或常压化学电离(APCI)的单质谱或串联质谱(MS)相结合被认为是食品和生物样品中辅酶q10鉴定和定量的金标准。然而,APCI产生的主要负极离子CoQ10自由基阴离子([M]•-,M /z 862.684)所表现出的特征性断裂尚未得到详细研究。在这项工作中,我们利用高碰撞能量解离(HCD)与高分辨率串联FTMS和碰撞诱导解离-低分辨率序列质谱(CID-MSn, n = 2-4)进行了系统的研究来澄清这一问题。通过密度泛函理论(DFT)计算,我们成功地解释了各种碎片化途径,并对产物离子的一些结构进行了检查。除了已知的直接发生在辅酶q10阴离子上的甲基自由基脱落,并导致[M - CH3]-和[M - 2CH3]•-等离子外,还初步提出沿低聚类异戊二烯侧链的C-C键均裂来解释一些观察到的断裂。因此,产生罕见但潜在稳定的双离子阴离子是假设的,其中一些可能经历分子内环化以产生没有不成对电子的离子。诊断产物离子出现于CoQ10的破碎过程中,并且与其他CoQn衍生物的自由基阴离子相同(n = 7-9),便于通过反相液相色谱(RPLC)-APCI-FTMS在可食用的芸苔科植物微绿色提取物中进行鉴定。
{"title":"Gas-Phase Fragmentation of Coenzyme Q<sub>10</sub> Radical Anion Generated by APCI: A Study by High/Low-Resolution Tandem/Sequential Mass Spectrometry.","authors":"Mariachiara Bianco, Ilario Losito, Giovanni Ventura, Beniamino Leoni, Onofrio Davide Palmitessa, Massimiliano Renna, Pietro Santamaria, Cosima Damiana Calvano, Tommaso R I Cataldi","doi":"10.1021/jasms.4c00399","DOIUrl":"10.1021/jasms.4c00399","url":null,"abstract":"<p><p>Coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>) and closely related compounds with varying isoprenoid tail lengths (CoQ<sub><i>n</i></sub>, <i>n</i> = 6-9) are biochemical cofactors involved in many physiological processes, playing important roles in cellular respiration and energy production. Liquid chromatography (LC) coupled with single or tandem mass spectrometry (MS) using electrospray (ESI) or atmospheric pressure chemical ionization (APCI) is considered the gold standard for the identification and quantification of CoQ<sub>10</sub> in food and biological samples. However, the characteristic fragmentation exhibited by the CoQ<sub>10</sub> radical anion ([M]<sup>•</sup><sup>-</sup>, <i>m</i>/<i>z</i> 862.684), the prevailing ion generated by APCI in negative polarity, has not been studied in detail. In this work, a systematic study was carried out to clarify this issue, using higher collisional energy dissociation (HCD) with high-resolution tandem FTMS and collision-induced dissociation-low-resolution sequential mass spectrometry (CID-MS<sup><i>n</i></sup>, <i>n</i> = 2-4). Various fragmentation pathways were successfully interpreted, with some structures proposed for product ions checked using density functional theory (DFT) calculations. Besides the already-known detachments of methyl radicals occurring directly from the CoQ<sub>10</sub> radical anion and leading to ions like [M - CH<sub>3</sub>]<b><sup>-</sup></b> and [M - 2CH<sub>3</sub>]<sup>•-</sup>, the homolytic cleavage of C-C bonds along the oligo-isoprenoid side chain was tentatively proposed to explain some of the observed fragmentations. As a result, the generation of uncommon yet potentially stable distonic biradical anions was hypothesized, with some of them likely undergoing intramolecular cyclization to generate ions without unpaired electrons. Diagnostic product ions emerged from the fragmentation processes of CoQ<sub>10</sub> and were found to be common also to the radical anions of other CoQ<sub><i>n</i></sub> derivatives (<i>n</i> = 7-9), facilitating their identification in extracts of edible <i>Brassicaceae</i> plant microgreens by reversed-phase liquid chromatography (RPLC)-APCI-FTMS.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"318-328"},"PeriodicalIF":3.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-05Epub Date: 2025-01-20DOI: 10.1021/jasms.4c00410
Caraleigh G Smith, Brian H Clowers, Steven J Kregel
In this communication we report the construction of a printed circuit board which mounts directly to the vacuum chamber of a mass spectrometer and produces the RF waveforms needed by many nonmass-selective devices such as ion guides and ion funnels. Our device is designed to replace a standard KF40 flange, can maintain vacuum chamber pressures of less than 10-6 Torr, and contains the circuitry of the open-source Wisconsin Oscillator RF power supply to generate RF waveforms of 1-4 MHz and up to 200 Vp-p. In this iteration of the Wisconsin Oscillator, we also introduce a variable resistor to control the output RF amplitude and show that its ion transmission capabilities are identical to those provided by commercial RF power supplies. With this new implementation we have greatly reduced the space and monetary requirements for driving nonmass-selective ion manipulation devices, which we expect to be advantageous to those developing low-cost and/or portable mass spectrometry systems.
{"title":"A Hybrid Vacuum Flange RF Oscillator for Low-Cost Mass Spectrometry.","authors":"Caraleigh G Smith, Brian H Clowers, Steven J Kregel","doi":"10.1021/jasms.4c00410","DOIUrl":"10.1021/jasms.4c00410","url":null,"abstract":"<p><p>In this communication we report the construction of a printed circuit board which mounts directly to the vacuum chamber of a mass spectrometer and produces the RF waveforms needed by many nonmass-selective devices such as ion guides and ion funnels. Our device is designed to replace a standard KF40 flange, can maintain vacuum chamber pressures of less than 10<sup>-6</sup> Torr, and contains the circuitry of the open-source Wisconsin Oscillator RF power supply to generate RF waveforms of 1-4 MHz and up to 200 V<sub>p-p</sub>. In this iteration of the Wisconsin Oscillator, we also introduce a variable resistor to control the output RF amplitude and show that its ion transmission capabilities are identical to those provided by commercial RF power supplies. With this new implementation we have greatly reduced the space and monetary requirements for driving nonmass-selective ion manipulation devices, which we expect to be advantageous to those developing low-cost and/or portable mass spectrometry systems.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"236-240"},"PeriodicalIF":3.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1021/jasms.4c0028610.1021/jasms.4c00286
Ishira Samarasinghe, Julius Pavlov and Athula B. Attygalle*,
Atmospheric-pressure chemical ionization mass spectrometry (APCI-MS) is a widely used technique for the analysis of a diverse range of analytes. Under APCI conditions, a nonthermal plasma, rich in highly oxidative species such as H2O2, O3, atomic O, and radicals such as HO•, is created. These oxidants trigger unanticipated and often undesirable chemical reactions within the ion source. For example, when aniline was introduced into this environment, it initially underwent oxidative dimerization forming hydrazobenzene (m/z 185). However, with prolonged exposure, there was a marked increase in total ion abundance and the generation of additional artifact ions such as protonated azobenzene (m/z 183) and protonated azoxybenzene (m/z 199). The emergence of these artifacts was found to be highly dependent on the corona-current magnitude. Moreover, the desorption-gas temperature significantly influenced the rate of artifact generation. Recognizing and acknowledging the formation and presence of such artifacts in an ion source is paramount in conducting validated chemical analysis. The existence of artifacts can complicate mass spectral interpretation, potentially leading to erroneous conclusions and misinterpretations of both qualitative and quantitative data. Thus, understanding the intricacies of nonthermal plasma-driven artifact formation is critical for accurate analytical outcomes.
{"title":"Unexpected Artifact Formation in Mass Spectrometric Analysis of Aniline under Atmospheric-Pressure Chemical Ionization","authors":"Ishira Samarasinghe, Julius Pavlov and Athula B. Attygalle*, ","doi":"10.1021/jasms.4c0028610.1021/jasms.4c00286","DOIUrl":"https://doi.org/10.1021/jasms.4c00286https://doi.org/10.1021/jasms.4c00286","url":null,"abstract":"<p >Atmospheric-pressure chemical ionization mass spectrometry (APCI-MS) is a widely used technique for the analysis of a diverse range of analytes. Under APCI conditions, a nonthermal plasma, rich in highly oxidative species such as H<sub>2</sub>O<sub>2</sub>, O<sub>3</sub>, atomic O, and radicals such as HO<sup>•</sup>, is created. These oxidants trigger unanticipated and often undesirable chemical reactions within the ion source. For example, when aniline was introduced into this environment, it initially underwent oxidative dimerization forming hydrazobenzene (<i>m</i>/<i>z</i> 185). However, with prolonged exposure, there was a marked increase in total ion abundance and the generation of additional artifact ions such as protonated azobenzene (<i>m</i>/<i>z</i> 183) and protonated azoxybenzene (<i>m</i>/<i>z</i> 199). The emergence of these artifacts was found to be highly dependent on the corona-current magnitude. Moreover, the desorption-gas temperature significantly influenced the rate of artifact generation. Recognizing and acknowledging the formation and presence of such artifacts in an ion source is paramount in conducting validated chemical analysis. The existence of artifacts can complicate mass spectral interpretation, potentially leading to erroneous conclusions and misinterpretations of both qualitative and quantitative data. Thus, understanding the intricacies of nonthermal plasma-driven artifact formation is critical for accurate analytical outcomes.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"463–472 463–472"},"PeriodicalIF":3.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Faces of Mass Spectrometry/Jose Navarrete-Perea.","authors":"Anne Brenner, J D Brookbank","doi":"10.1021/jasms.5c00020","DOIUrl":"https://doi.org/10.1021/jasms.5c00020","url":null,"abstract":"","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-04DOI: 10.1021/jasms.5c0002010.1021/jasms.5c00020
Anne Brenner, and , J. D. Brookbank,
{"title":"Faces of Mass Spectrometry/Jose Navarrete-Perea","authors":"Anne Brenner, and , J. D. Brookbank, ","doi":"10.1021/jasms.5c0002010.1021/jasms.5c00020","DOIUrl":"https://doi.org/10.1021/jasms.5c00020https://doi.org/10.1021/jasms.5c00020","url":null,"abstract":"","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"450–452 450–452"},"PeriodicalIF":3.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-03DOI: 10.1021/jasms.4c0038210.1021/jasms.4c00382
Christian A. Rosales, Noah A. Lepinsky, Wondewossen Gebeyehu, Karl V. Wasslen, Fraser Colquhoun, Benjamin B. Warnes, Jasmine Chihabi, Jeffrey M. Manthorpe* and Jeffrey C. Smith*,
Substances of misuse are becoming increasingly difficult to analyze as unique methods of smuggling are adopted and due to the rapid emergence of new psychoactive substances, increasing the pool of compounds to characterize and identify. Technologies such as gas chromatography and liquid chromatography coupled to mass spectrometry (MS) represent the gold standard for accurate and robust analysis, with on-site ambient- and portable-MS systems providing rapid methods of drug screening and testing. For many samples containing residual analyte quantities, methods to improve sensitivity through chemical derivatization are critical for accurate determination. Herein, we demonstrate for the first time the use of trimethylation enhancement using diazomethane (TrEnDi) to improve the MS-based sensitivity of 13 different drugs of misuse. All analytes were successfully permethylated, with 11 demonstrating improved analytical characteristics from TrEnDi with MS sensitivity enhancements ranging from 1.2-fold to as high as 24.2-fold in the case of psilocybin, as well as increases in reversed-phase chromatographic retention for most species. Derivatization using 13C-isotopically labeled TrEnDi reagents were used to successfully resolve isobaric interference issues between three pairs of controlled substances. By using an unconventional aprotic solvent system for electrospray ionization, the benefit of a fixed-permanent positive charge was highlighted as TrEnDi-modified amphetamine was easily measured while unmodified was not detected. Finally, TrEnDi was employed to boost the sensitivity of morphine in a real urine matrix. Our results demonstrate a percent recovery of 103.1% and a sensitivity enhancement of 2.4-fold, demonstrating the versatility and applicability of TrEnDi to pre-existing analytical workflows for trace analysis.
{"title":"Improved LC-MS Detection of Opioids, Amphetamines, and Psychedelics Using TrEnDi","authors":"Christian A. Rosales, Noah A. Lepinsky, Wondewossen Gebeyehu, Karl V. Wasslen, Fraser Colquhoun, Benjamin B. Warnes, Jasmine Chihabi, Jeffrey M. Manthorpe* and Jeffrey C. Smith*, ","doi":"10.1021/jasms.4c0038210.1021/jasms.4c00382","DOIUrl":"https://doi.org/10.1021/jasms.4c00382https://doi.org/10.1021/jasms.4c00382","url":null,"abstract":"<p >Substances of misuse are becoming increasingly difficult to analyze as unique methods of smuggling are adopted and due to the rapid emergence of new psychoactive substances, increasing the pool of compounds to characterize and identify. Technologies such as gas chromatography and liquid chromatography coupled to mass spectrometry (MS) represent the gold standard for accurate and robust analysis, with on-site ambient- and portable-MS systems providing rapid methods of drug screening and testing. For many samples containing residual analyte quantities, methods to improve sensitivity through chemical derivatization are critical for accurate determination. Herein, we demonstrate for the first time the use of trimethylation enhancement using diazomethane (TrEnDi) to improve the MS-based sensitivity of 13 different drugs of misuse. All analytes were successfully permethylated, with 11 demonstrating improved analytical characteristics from TrEnDi with MS sensitivity enhancements ranging from 1.2-fold to as high as 24.2-fold in the case of psilocybin, as well as increases in reversed-phase chromatographic retention for most species. Derivatization using <sup>13</sup>C-isotopically labeled TrEnDi reagents were used to successfully resolve isobaric interference issues between three pairs of controlled substances. By using an unconventional aprotic solvent system for electrospray ionization, the benefit of a fixed-permanent positive charge was highlighted as TrEnDi-modified amphetamine was easily measured while unmodified was not detected. Finally, TrEnDi was employed to boost the sensitivity of morphine in a real urine matrix. Our results demonstrate a percent recovery of 103.1% and a sensitivity enhancement of 2.4-fold, demonstrating the versatility and applicability of TrEnDi to pre-existing analytical workflows for trace analysis.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"514–523 514–523"},"PeriodicalIF":3.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-02DOI: 10.1021/jasms.4c0045510.1021/jasms.4c00455
Karen A. Reyes Monroy, Richard McCrary, Isabelle Parry, Catherine Webber, Teresa D. Golden and Guido F. Verbeck*,
Illicit fentanyl and fentanyl analogs are a growing concern in the United States as opioid related deaths rise. Given that fentanyl analogs are readily obtained by modifying the structure of fentanyl, illicit fentanyl analogs appearing on the black market often contain similar structures, making analogue differentiation and identification difficult. Thus, obtaining both precursor and product ion data during analysis is becoming increasingly valuable in fentanyl analog characterization. In this paper, we provide GC column retention time, precursor, and product ion mass spectrum data for 74 fentanyl analogs that were analyzed using atmospheric pressure chemical ionization-gas chromatography–mass spectrometry (APCI-GC-MS) utilizing a triple quadrupole mass analyzer. During analysis, precursor ions underwent collision induced dissociation (CID) by increasing the collision energy (10, 20, 30, 40, and 50 V) throughout a single run. Data reveal that APCI readily produces product ions of the piperidine and N-alkyl chain but rarely provides data on the acyl group. Furthermore, fentanyl analogs with greater substitution at the N-alkyl chain demonstrate a greater preference for dissociation at the N-αC and αC-βC bond, while greater substitution at the amide group leads to fragmentation at the N–C4 bond.
{"title":"Analysis of Fentanyl and Fentanyl Analogs Using Atmospheric Pressure Chemical Ionization Gas Chromatography–Mass Spectrometry (APCI-GC-MS)","authors":"Karen A. Reyes Monroy, Richard McCrary, Isabelle Parry, Catherine Webber, Teresa D. Golden and Guido F. Verbeck*, ","doi":"10.1021/jasms.4c0045510.1021/jasms.4c00455","DOIUrl":"https://doi.org/10.1021/jasms.4c00455https://doi.org/10.1021/jasms.4c00455","url":null,"abstract":"<p >Illicit fentanyl and fentanyl analogs are a growing concern in the United States as opioid related deaths rise. Given that fentanyl analogs are readily obtained by modifying the structure of fentanyl, illicit fentanyl analogs appearing on the black market often contain similar structures, making analogue differentiation and identification difficult. Thus, obtaining both precursor and product ion data during analysis is becoming increasingly valuable in fentanyl analog characterization. In this paper, we provide GC column retention time, precursor, and product ion mass spectrum data for 74 fentanyl analogs that were analyzed using atmospheric pressure chemical ionization-gas chromatography–mass spectrometry (APCI-GC-MS) utilizing a triple quadrupole mass analyzer. During analysis, precursor ions underwent collision induced dissociation (CID) by increasing the collision energy (10, 20, 30, 40, and 50 V) throughout a single run. Data reveal that APCI readily produces product ions of the piperidine and <i>N</i>-alkyl chain but rarely provides data on the acyl group. Furthermore, fentanyl analogs with greater substitution at the <i>N</i>-alkyl chain demonstrate a greater preference for dissociation at the N-αC and αC-βC bond, while greater substitution at the amide group leads to fragmentation at the N–C4 bond.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"587–600 587–600"},"PeriodicalIF":3.1,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jasms.4c00455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1021/jasms.4c0038910.1021/jasms.4c00389
Emmajay Sutherland, Tim S. Veth and Nicholas M. Riley*,
Deamidation of asparagine and glutamine residues occurs spontaneously, is influenced by pH, temperature, and incubation time, and can be accelerated by adjacent amino acid residues. Incubation conditions used for proteolytic digestion in bottom-up proteomic studies can induce significant deamidation that affects results, either knowingly or unknowingly. This has prompted studies into modifications to common trypsin digestion protocols to minimize chemical deamidation, including shorter incubation times and specific lysis buffers. Prior work suggested ammonium acetate at pH 6 to minimize chemical deamidation, but this buffer has compatibility issues with trypsin digestion and common assays (e.g., bicinchoninic acid assays). Here, we re-evaluated former comparisons of Tris-HCl, ammonium bicarbonate, and triethylammonium bicarbonate buffers for the amount of artificial, chemically induced deamidation generated in a standard bottom-up proteomics workflow, and we added an evaluation of three commonly used and biologically compatible buffers, HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), EPPS (3-[4-(2-Hydroxyethyl)piperazin-1-yl]propane-1-sulfonic acid), and PBS (phosphate buffered saline). Our findings show that HEPES exhibited the least amount of artificial deamidation and is a reasonable choice for general proteomic experiments, especially for studies considering N-glycosylation.
{"title":"Revisiting the Effect of Trypsin Digestion Buffers on Artificial Deamidation","authors":"Emmajay Sutherland, Tim S. Veth and Nicholas M. Riley*, ","doi":"10.1021/jasms.4c0038910.1021/jasms.4c00389","DOIUrl":"https://doi.org/10.1021/jasms.4c00389https://doi.org/10.1021/jasms.4c00389","url":null,"abstract":"<p >Deamidation of asparagine and glutamine residues occurs spontaneously, is influenced by pH, temperature, and incubation time, and can be accelerated by adjacent amino acid residues. Incubation conditions used for proteolytic digestion in bottom-up proteomic studies can induce significant deamidation that affects results, either knowingly or unknowingly. This has prompted studies into modifications to common trypsin digestion protocols to minimize chemical deamidation, including shorter incubation times and specific lysis buffers. Prior work suggested ammonium acetate at pH 6 to minimize chemical deamidation, but this buffer has compatibility issues with trypsin digestion and common assays (e.g., bicinchoninic acid assays). Here, we re-evaluated former comparisons of Tris-HCl, ammonium bicarbonate, and triethylammonium bicarbonate buffers for the amount of artificial, chemically induced deamidation generated in a standard bottom-up proteomics workflow, and we added an evaluation of three commonly used and biologically compatible buffers, HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), EPPS (3-[4-(2-Hydroxyethyl)piperazin-1-yl]propane-1-sulfonic acid), and PBS (phosphate buffered saline). Our findings show that HEPES exhibited the least amount of artificial deamidation and is a reasonable choice for general proteomic experiments, especially for studies considering N-glycosylation.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"457–462 457–462"},"PeriodicalIF":3.1,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Remembrance: Dr. Jean H. Futrell.","authors":"Richard D Smith, David W Koppenaal","doi":"10.1021/jasms.4c00479","DOIUrl":"https://doi.org/10.1021/jasms.4c00479","url":null,"abstract":"","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}