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A simple, rapid and cost-effective UHPLC–MS/MS method for simultaneous quantitation of seven antiepileptic drugs/metabolites in human serum 一种简便、快速、经济高效的UHPLC-MS /MS同时定量人血清中七种抗癫痫药物/代谢物的方法
IF 3.4 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-09-13 DOI: 10.1016/j.jmsacl.2025.09.001
Xiaowei Fu, Xiangtang Li, Hui He

Background

Epilepsy affects approximately 50 million people worldwide. Antiepileptic drugs (AEDs) are the mainstream treatment. Therapeutic drug monitoring (TDM) of AEDs is necessary to maximize efficacy and minimize toxicity. We report a simple, rapid, and cost-effective ultra-performance liquid chromatography-mass spectrometry method that can simultaneously measure seven AEDs/metabolites, including levetiracetam (LEV), lacosamide (LCM), zonisamide (ZON), lamotrigine (LMT), 10-hydroxycarbazepine (OXC-M1), clobazam (CLO), and N-desmethyl clobazam (N-CLB) in serum.

Method

Only 20 µl of serum was used with simple protein precipitation and dilution. Analysis was performed on a SCIEX 6500 UHPLC–MS/MS in positive ion mode. Separation was performed on a C18 reversed-phase column using a gradient. The seven AEDs/metabolites were eluted in 4.5 min.

Results

The assay was linear over the concentration ranges 0.4–100 µg/mL for LEV, 0.12–30 µg/mL for LMT, 0.12–30 µg/mL for LCM, 0.32–80 µg/mL for ZON, 0.28–70 µg/mL for OXC-M1, and 7.82–2000 ng/mL for CLO, 78.2–20000 ng/mL for N-CLB, respectively, with correlation coefficient greater than 0.99. Recovery was from 88 to 108 %. Intra and inter assay precision for three levels of quality controls were from 2.1 to 6.8 % and 4.2 to 10.9 %, respectively. The accuracy was evaluated by comparing with the College of American Pathologists survey results, and a correlation coefficient greater than 0.96 was observed. The absence of matrix effects was also confirmed.

Conclusion

We have developed and validated a simple, rapid, and cost-effective UHPLC–MS/MS method for the simultaneous quantitation of seven AEDs/metabolites in serum within a 4.5-min analysis time. It has been implemented in our children’s hospital with same-day turnaround time.
全世界约有5000万人患有癫痫。抗癫痫药物(AEDs)是主流的治疗方法。治疗性药物监测(TDM)是实现抗癫痫药疗效最大化和毒性最小化的必要手段。本文报道了一种简单、快速、经济高效的超高效液相色谱-质谱联用方法,可同时测定血清中7种AEDs/代谢物,包括左乙拉西坦(LEV)、拉科沙胺(LCM)、唑尼沙胺(ZON)、拉莫三嗪(LMT)、10-羟基卡西平(OXC-M1)、氯巴唑(CLO)和n -二甲基氯巴唑(N-CLB)。方法仅用20µl血清进行简单的蛋白沉淀稀释。在SCIEX 6500 UHPLC-MS /MS上进行正离子模式分析。在C18反相柱上使用梯度进行分离。7种aed /代谢物在4.5 min内洗脱。结果LEV、LMT、LCM、ZON、OXC-M1、CLO、N-CLB分别在0.4 ~ 100µg/mL、0.12 ~ 30µg/mL、0.32 ~ 80µg/mL、0.28 ~ 70µg/mL、7.82 ~ 2000 ng/mL、78.2 ~ 20000 ng/mL浓度范围内呈线性关系,相关系数均大于0.99。回收率为88% ~ 108%。三级质量控制的内、间精密度分别为2.1 ~ 6.8%和4.2 ~ 10.9%。与美国病理学家学会调查结果进行比较,相关系数大于0.96。也证实了不存在基质效应。结论建立了一种高效液相色谱-质谱联用(UHPLC-MS /MS)方法,可在4.5 min的分析时间内同时测定血清中7种aed /代谢物。它已在我们的儿童医院实施,当日周转时间。
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引用次数: 0
Corrigendum to “A rapid method for determination of rosuvastatin in blood plasma with supported liquid extraction” [J. Mass Spectromet. Adv. Clin. Lab 36 (2025) 29–36] “支持液体萃取法快速测定血浆中瑞舒伐他汀”的勘误[J]。Spectromet质量。放置中国。实验室36 (2025)29-36]
IF 3.4 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-09-02 DOI: 10.1016/j.jmsacl.2025.08.001
Tjaša Dermota , Mojca Božič Mijovski , Jurij Trontelj
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引用次数: 0
Evaluation of the detuning ratio as a tool to detect potential interference in LC-MSMS analysis 失谐比作为LC-MSMS分析中潜在干扰检测工具的评价
IF 3.1 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-07-18 DOI: 10.1016/j.jmsacl.2025.07.002
Arber Rexhaj , Michael Vogeser , Katharina Habler

Objective

Tandem mass spectrometry (MS/MS) is highly specific in principle, but there is always the possibility of interference due to unexpected substances in the samples that have the identical mass transitions as the target analytes (isomeric/isobaric interferences). By recording the ion ratio (IR), clinical laboratories already widely attempt to identify such interferences in individual cases. To supplement this procedure, differential tuning effects can be assessed. We aimed to evaluate this approach experimentally.

Methods

The detuning ratio (DR) is based on the differential influences of MS instrument settings on the ion yield of a respective target analyte; isomeric or isobaric interferences can lead to a shift of the DR for an affected sample. By determining the DR in samples in which known isomeric interference substances have been spiked to the target analyte, the applicability of DR detection was quantitatively investigated.

Results

It was observed in two independent exemplary test systems (Cortisone / Prednisolone and O-Desmethylvenlafaxine / cis-Tramadol HCl) that a DR can indicate the presence of isomeric interferences.

Conclusion

It was confirmed that a DR can be used as a method to obtain indications of the presence of isomeric or isobaric interferences in individual samples in an analytical LC-MS/MS system; the technique can be used in addition to the established method of IR detection to increase the analytical reliability of clinical MS analyses.
Abbreviations: CE, collision energy; CID, collision induced dissociation; CXP, cell exit potential; CLSI, Clinical and Laboratory Standards Institute; DR, detuning ratio; ESI+, positive electrospray ionization; IR, ion ratio; IS, internal standard; LC, liquid chromatographic; LC-MS/MS, liquid chromatography tandem mass spectrometry; ME, matrix effects; MRM, multiple reaction monitoring; MS, mass spectrometry; m/z, mass-to-charge ratio; TIC, Total ion current.
目的:串联质谱法(MS/MS)在原理上具有高度的特异性,但由于样品中存在与目标分析物具有相同质量跃迁的意外物质(异构/等压干扰),始终存在干扰的可能性。通过记录离子比(IR),临床实验室已经广泛尝试在个体病例中识别这种干扰。为了补充这个过程,可以评估差分调谐效果。我们的目的是通过实验来评估这种方法。方法失谐比(DR)是基于质谱仪器设置对不同目标分析物离子产率的不同影响;同分异构体或等压干扰可导致受影响样品的DR偏移。通过测定已知同分异构体干扰物质加标到目标分析物的样品中的DR,定量研究了DR检测的适用性。结果在两个独立的示例性测试系统(可的松/强的松和o -去甲基文拉法辛/顺式曲马多HCl)中观察到DR可以指示异构体干扰的存在。结论在LC-MS/MS分析系统中,DR可以作为一种方法获得样品中异构体或等压干扰的迹象;该技术可用于已建立的红外检测方法之外,以提高临床质谱分析的分析可靠性。缩写:CE,碰撞能量;CID:碰撞诱导解离;CXP,细胞退出电位;CLSI,临床和实验室标准协会;DR:失谐比;ESI+,正电喷雾电离;IR,离子比;IS,内标;LC,液相色谱;LC-MS/MS,液相色谱串联质谱;ME:矩阵效应;MRM,多反应监测;质谱法;M /z:质荷比;总离子电流。
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引用次数: 0
Urine methamphetamine-to-amphetamine ratio by LC-MS/MS to differentiate methamphetamine use from pharmaceutical impurity in patients prescribed amphetamine 采用LC-MS/MS鉴别处方安非他明患者的尿甲基苯丙胺与药物杂质
IF 3.1 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-07-11 DOI: 10.1016/j.jmsacl.2025.07.001
Lindsey Contella , Phillip Kang , Clara E. Wolf , Victoria L. Thomas , Melissa Gildenberg , Marion L. Snyder , Stacy E.F. Melanson , Nicole V. Tolan

Introduction

Patients compliant with prescribed amphetamine (AMPH) should not have detectable methamphetamine (METH) in their urine; detectable METH typically indicates illicit use. However, we have identified patients with results suggestive of METH as an impurity in prescribed AMPH.

Objectives

Derive a METH:AMPH ratio cut-off from a training set of patients compliant with AMPH prescriptions to differentiate METH as an impurity from illicit use.

Methods

Retrospective review of AMPH and METH-positive cases by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at Brigham and Women’s Hospital (BWH) and Luxor Scientific. Correlated results with clinical and medication history and compliance with prescribed medications.

Results

The median ± interquartile range (IQR) METH:AMPH ratio for the Adderall training sets was 0.43 ± 0.31 % and 0.05 ± 0.040 %, with a maximum ratio of 1.125 % and 0.125 % at BWH and Luxor, respectively. The median ± IQR METH:AMPH ratio for the Luxor d-AMPH training set was 0.039 ± 0.028 %, with a maximum ratio of 0.09 %; not statistically different from the Adderall training set. Assessment of the BWH test set where METH < AMPH (n = 22) revealed that METH was likely due to an impurity (n = 10), distant METH mis/use (n = 11), or requiring further analysis (n = 1). METH was also detected by LC-MS/MS in a commercial AMPH calibrator and in Adderall XR.

Discussion

METH may represent an impurity in the AMPH formulation. Laboratories are encouraged to define a METH:AMPH ratio below which an impurity is the likely explanation for METH and/or to increase the METH positivity cut-off to 50 or 100 ng/mL to reduce potential false-accusations of illicit METH use.
服用处方安非他明(AMPH)的患者尿液中不应检测到甲基苯丙胺(METH);可检测到的冰毒通常表明非法使用。然而,我们已经确定患者的结果提示甲基苯丙胺作为处方AMPH的杂质。目的:从符合AMPH处方的患者训练集中得出甲基苯丙胺:AMPH比率截止值,以区分甲基苯丙胺作为杂质与非法使用。方法采用液相色谱-串联质谱法(LC-MS/MS)对布里格姆妇女医院(BWH)和卢克索科学公司(Luxor Scientific)的AMPH和meth阳性病例进行回顾性分析。结果与临床、用药史及遵医嘱相关。结果Adderall训练集的METH:AMPH比值中位数±四分位数范围(IQR)分别为0.43±0.31%和0.05±0.040%,其中BWH和Luxor训练集的最大值分别为1.125%和0.125%。Luxor d-AMPH训练集的中位数±IQR METH:AMPH比值为0.039±0.028%,最大值为0.09%;与阿得拉训练集没有统计学差异。对BWH测试集的评估,其中METH <;AMPH (n = 22)显示甲基安非他明可能是由于杂质(n = 10),远距离甲基安非他明误用(n = 11)或需要进一步分析(n = 1)。在商用AMPH校准器和Adderall XR中也采用LC-MS/MS检测甲基苯丙胺。甲基安非他明可能代表AMPH制剂中的杂质。鼓励实验室确定一个甲基安非他明:AMPH比率,低于该比率的杂质可能是甲基安非他明的原因,和/或将甲基安非他明的阳性截止值提高到50或100纳克/毫升,以减少非法使用甲基安非他明的潜在错误指控。
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引用次数: 0
Development of an LC-MS/MS method for quantification of colistin and colistin methanesulfonate in human plasma and its application to stability studies and therapeutic drug monitoring LC-MS/MS法测定人血浆中粘菌素和粘菌素甲磺酸的含量及其在稳定性研究和治疗药物监测中的应用
IF 3.1 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-06-01 DOI: 10.1016/j.jmsacl.2025.05.001
Tinghui Zhao , Lu Liu , Guangjie Yang , Hengyi Yu , Lihui Qiu , Xiping Li , Dong Xiang , Xuepeng Gong

Introduction

Colistin serves as the last line of defense against multidrug-resistant Gram-negative bacterial infections and is commonly administered in clinical practice as its prodrug, colistin methanesulfonate (CMS). However, due to its notable nephrotoxicity and narrow therapeutic window, therapeutic drug monitoring (TDM) is essential.

Objectives

To develop an optimal LC-MS/MS method for the quantification of colistin and CMS in human plasma and to apply it to stability studies and TDM.

Methods

Colistin A, colistin B, and internal standard (IS, polymyxin B2) were extracted from plasma using solid phase extraction columns. Sample separation was performed using a Welch Ultimate LP-C18 column with a 5-minute gradient elution consisting of water and acetonitrile, both supplied with 1.0% formic acid. The CMS concentration was obtained by comparing the total amount of colistin in acid-hydrolyzed and non-acid-hydrolyzed plasma.

Results

Colistin A and colistin B showed excellent linearity in the concentration range of 0.1–10.0 μg/mL (R2 > 0.995) with acceptable specificity, accuracy (90.97 %–114.65 %), precision (RSD < 15 %), matrix effect (RSD < 15 %), and recovery (91.93 %–100.93 %). CMS in five commonly used clinical infusion solutions was stable when stored at room temperature for 8 h or at 4 °C for 24 h. The whole blood and plasma samples of CMS are susceptible to degradation at room temperature but are stable on ice. Plasma concentrations of colistin and CMS were accurately determined in three critically ill patients.

Conclusion

The method we have developed is robust and streamlined, and has successfully demonstrated the potential feasibility for future TDM applications of colistin and CMS in critically ill patients.
粘菌素是抵抗多重耐药革兰氏阴性细菌感染的最后一道防线,在临床实践中通常作为其前药粘菌素甲磺酸(CMS)给药。然而,由于其显著的肾毒性和狭窄的治疗窗口,治疗药物监测(TDM)是必不可少的。目的建立hplc -MS/MS定量测定人血浆中粘菌素和CMS的最佳方法,并将其应用于稳定性研究和TDM。方法采用固相萃取柱从血浆中提取黏菌素A、黏菌素B和内标(IS、多粘菌素B2)。样品采用Welch Ultimate LP-C18色谱柱进行分离,用1.0%甲酸的水和乙腈梯度洗脱5分钟。通过比较酸水解和非酸水解血浆中粘菌素的总量,得出CMS浓度。结果黏菌素A和黏菌素B在0.1 ~ 10.0 μg/mL范围内呈良好的线性关系(R2 >;0.995)具有可接受的特异性、准确度(90.97% ~ 114.65%)、精密度(RSD <;15%)、矩阵效应(RSD <;回收率为91.93% ~ 100.93%。5种常用的临床输液液中CMS在室温下保存8 h或在4℃下保存24 h时均保持稳定。CMS的全血和血浆样品在室温下易降解,但在冰上保持稳定。准确测定3例危重患者血浆粘菌素和CMS浓度。结论该方法稳健、简便,为粘菌素和CMS在危重患者TDM中的应用提供了潜在的可行性。
{"title":"Development of an LC-MS/MS method for quantification of colistin and colistin methanesulfonate in human plasma and its application to stability studies and therapeutic drug monitoring","authors":"Tinghui Zhao ,&nbsp;Lu Liu ,&nbsp;Guangjie Yang ,&nbsp;Hengyi Yu ,&nbsp;Lihui Qiu ,&nbsp;Xiping Li ,&nbsp;Dong Xiang ,&nbsp;Xuepeng Gong","doi":"10.1016/j.jmsacl.2025.05.001","DOIUrl":"10.1016/j.jmsacl.2025.05.001","url":null,"abstract":"<div><h3>Introduction</h3><div>Colistin serves as the last line of defense against multidrug-resistant Gram-negative bacterial infections and is commonly administered in clinical practice as its prodrug, colistin methanesulfonate (CMS). However, due to its notable nephrotoxicity and narrow therapeutic window, therapeutic drug monitoring (TDM) is essential.</div></div><div><h3>Objectives</h3><div>To develop an optimal LC-MS/MS method for the quantification of colistin and CMS in human plasma and to apply it to stability studies and TDM.</div></div><div><h3>Methods</h3><div>Colistin A, colistin B, and internal standard (IS, polymyxin B2) were extracted from plasma using solid phase extraction columns. Sample separation was performed using a Welch Ultimate LP-C18 column with a 5-minute gradient elution consisting of water and acetonitrile, both supplied with 1.0% formic acid. The CMS concentration was obtained by comparing the total amount of colistin in acid-hydrolyzed and non-acid-hydrolyzed plasma.</div></div><div><h3>Results</h3><div>Colistin A and colistin B showed excellent linearity in the concentration range of 0.1–10.0 μg/mL (R<sup>2</sup> &gt; 0.995) with acceptable specificity, accuracy (90.97 %–114.65 %), precision (RSD &lt; 15 %), matrix effect (RSD &lt; 15 %), and recovery (91.93 %–100.93 %). CMS in five commonly used clinical infusion solutions was stable when stored at room temperature for 8 h or at 4 °C for 24 h. The whole blood and plasma samples of CMS are susceptible to degradation at room temperature but are stable on ice. Plasma concentrations of colistin and CMS were accurately determined in three critically ill patients.</div></div><div><h3>Conclusion</h3><div>The method we have developed is robust and streamlined, and has successfully demonstrated the potential feasibility for future TDM applications of colistin and CMS in critically ill patients.</div></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"37 ","pages":"Pages 39-48"},"PeriodicalIF":3.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “A liquid chromatography-high-resolution mass spectrometry method for separation and identification of hemoglobin variant subunits with mass shifts less than 1 Da” [J. Mass Spectromet. Adv. Clin. Lab 35 (2025) 1–7] “液相色谱-高分辨率质谱法分离鉴定质量位移小于1 Da的血红蛋白变异亚基”的勘误[J]。Spectromet质量。放置中国。实验室35 (2025)1-7]
IF 3.1 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-05-09 DOI: 10.1016/j.jmsacl.2025.04.009
Ainslie Chen , Ryan M. Aquino , Hector A. Vidal , Carolyn V. Wong , Ruben Y. Luo
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引用次数: 0
Enhanced identification of Morganella spp. using MALDI-TOF mass spectrometry MALDI-TOF质谱法对摩根菌的强化鉴定
IF 3.1 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-05-03 DOI: 10.1016/j.jmsacl.2025.04.011
Mathilde Duque , Cécile Emeraud , Rémy A. Bonnin , Quentin Giai-Gianetto , Laurent Dortet , Alexandre Godmer

Introduction

The genus Morganella, including clinically isolated species M. sibonii and M. morganii, has a still underexplored role in clinical microbiology. Despite the clinical relevance of Morganella spp., current MALDI-TOF commercial systems fail to differentiate these species. Whole genome sequencing (WGS) remains the most effective method to distinguish species. However, this method is not adapted for routine lab workflow. Enhancing MALDI-TOF’s accuracy could make it a rapid and effective approach for distinguishing Morganella species in routine laboratory diagnostics.

Objectives

This study aims to improve the performance of MALDI-TOF for identifying Morganella spp. using WGS as the gold-standard reference method.

Methods

We applied Machine Learning (ML) algorithms to a collection of 235 clinicial Morganella spp. strains to develop an optimized identification model. Whole genome sequencing was used to characterize these strains and perform phylogenetic analysis, categorizing 209 strains as M. morganii and 26 as M. sibonii.

Results

The ML-based classifiers showed improved identification accuracy (44 of the 160 designed with accuracy at 1). Also, MS analysis identified 11 peaks able to discriminate between M. morganii and M. sibonii.

Conclusion

Through development of a publicly-available online ML-based classifier, this study has improved the capacity of MALDI-TOF for distinguishing Morganella spp., providing a reliable, user-friendly solution suited to routine clinical diagnostics and supporting a better understanding of the roles of M. morganii and M. sibonii in human pathology.
摩根氏菌属,包括临床分离种M. sibonii和M. morganii,在临床微生物学中的作用尚未得到充分的探索。尽管摩根菌属具有临床意义,但目前的MALDI-TOF商业系统无法区分这些物种。全基因组测序(WGS)仍然是区分物种最有效的方法。然而,这种方法并不适用于常规的实验室工作流程。提高MALDI-TOF的准确性可使其成为实验室常规诊断中快速有效的莫氏菌种类鉴别方法。目的以WGS为金标准参比法,提高MALDI-TOF鉴别摩根氏菌的性能。方法采用机器学习(ML)算法对235株临床摩根氏菌进行筛选,建立优化的鉴定模型。利用全基因组测序对这些菌株进行鉴定并进行系统发育分析,其中209株为莫氏分枝杆菌,26株为西伯利亚分枝杆菌。结果基于ml的分类器具有较好的识别精度(160个分类器中有44个的识别精度为1)。此外,质谱分析还鉴定出11个峰可以区分M. morganii和M. sibonii。通过开发一个公开可用的基于ml的在线分类器,本研究提高了MALDI-TOF区分摩根氏杆菌的能力,提供了一个可靠的、用户友好的解决方案,适合常规临床诊断,并支持更好地了解摩根氏分枝杆菌和西伯利亚分枝杆菌在人类病理中的作用。
{"title":"Enhanced identification of Morganella spp. using MALDI-TOF mass spectrometry","authors":"Mathilde Duque ,&nbsp;Cécile Emeraud ,&nbsp;Rémy A. Bonnin ,&nbsp;Quentin Giai-Gianetto ,&nbsp;Laurent Dortet ,&nbsp;Alexandre Godmer","doi":"10.1016/j.jmsacl.2025.04.011","DOIUrl":"10.1016/j.jmsacl.2025.04.011","url":null,"abstract":"<div><h3>Introduction</h3><div>The genus <em>Morganella,</em> including clinically isolated species <em>M. sibonii</em> and <em>M. morganii</em>, has a still underexplored role in clinical microbiology. Despite the clinical relevance of <em>Morganella</em> spp., current MALDI-TOF commercial systems fail to differentiate these species. Whole genome sequencing (WGS) remains the most effective method to distinguish species. However, this method is not adapted for routine lab workflow. Enhancing MALDI-TOF’s accuracy could make it a rapid and effective approach for distinguishing <em>Morganella</em> species in routine laboratory diagnostics.</div></div><div><h3>Objectives</h3><div>This study aims to improve the performance of MALDI-TOF for identifying <em>Morganella</em> spp. using WGS as the gold-standard reference method.</div></div><div><h3>Methods</h3><div>We applied Machine Learning (ML) algorithms to a collection of 235 clinicial <em>Morganella</em> <!-->spp. strains to develop an optimized identification model. Whole genome sequencing was used to characterize these strains and perform phylogenetic analysis, categorizing 209 strains as <em>M. morganii</em> and 26 as <em>M. sibonii</em>.</div></div><div><h3>Results</h3><div>The ML-based classifiers showed improved identification accuracy (44 of the 160 designed with accuracy at<!--> <!-->1). Also, MS analysis identified 11 peaks able to discriminate between <em>M. morganii</em> and <em>M. sibonii</em>.</div></div><div><h3>Conclusion</h3><div>Through development of a publicly-available online ML-based classifier, this study has improved the capacity of MALDI-TOF for distinguishing <em>Morganella</em> spp<em>.</em>, providing a reliable, user-friendly solution suited to routine clinical diagnostics and supporting a better understanding of the roles of <em>M. morganii</em> and <em>M. sibonii</em> in human pathology.</div></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"37 ","pages":"Pages 9-13"},"PeriodicalIF":3.1,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serum peptides as candidate biomarkers for relapsing polychondritis 血清多肽作为复发性多软骨炎的候选生物标志物
IF 3.1 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-04-30 DOI: 10.1016/j.jmsacl.2025.04.001
Toshiyuki Sato , Masaaki Sato , Kouhei Nagai , Masahiko Fukasawa , Yoshiaki Nagashima , Teisuke Uchida , Atsuhiro Tsutiya , Kazuki Omoteyama , Mitsumi Arito , Yukiko Takakuwa , Seido Ooka , Naoya Suematsu , Kimito Kawahata , Yoshihisa Yamano , Tomohiro Kato , Manae S. Kurokawa

Introduction

Relapsing polychondritis (RP) is an intractable disease characterized by recurrent inflammation of cartilaginous tissue throughout the body. It is difficult to accurately diagnose RP, and no useful biomarkers have yet been identified.

Objectives

We analyzed serum peptide profiles to identify novel candidate biomarkers for RP.

Methods

Thirty-seven patients with RP, 42 patients with rheumatoid arthritis (RA), and 35 healthy control (HC) subjects were divided into training and testing sets. Seven patients demonstrating granulomatosis with polyangiitis (GPA) were used for validation. The ion intensity of serum peptides was comprehensively measured by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry and applied to a supervised multivariate analysis. Peptides of interest were analyzed by liquid chromatography-tandem mass spectrometry.

Results

In the training set, models developed based on 11 (RP/HC-11P model), 9 (RP/RA-9P model), and 14 (RP/nonRP-14P model) peptides, out of 160 peptides detected were able to completely discriminate the RP group from the HC, RA, and nonRP (HC + RA) groups. Almost all of the 15 identified discriminatory peptides comprising these models were fragments of proteins associated with coagulation. Four models, each consisting of 4 out of 10 identified peptides of the RP/nonRP-14P model (models RP/nonRP-4P-2, -10, -11, and -38), provided ≥ 70.0 % sensitivity and specificity when applied to the validation set (the testing set and the GPA group) (AUROC, 0.779–0.815). Notably, the RP/nonRP-4P-2 model provided 83.3 % sensitivity and 71.7 % specificity in the validation set (AUROC, 0.802).

Conclusions

Serum peptides are useful as candidate biomarkers for discriminating RP and may be involved in the pathophysiology of RP.
复发性多软骨炎(RP)是一种以全身软骨组织反复发炎为特征的顽固性疾病。RP很难准确诊断,目前还没有发现有用的生物标志物。目的分析血清肽谱,以确定RP的新的候选生物标志物。方法将37例RP患者、42例类风湿关节炎(RA)患者和35例健康对照(HC)患者分为训练组和测试组。7例肉芽肿合并多血管炎(GPA)患者被用于验证。采用基质辅助激光解吸/电离飞行时间/飞行时间质谱法综合测量血清多肽的离子强度,并应用于监督多变量分析。目的肽通过液相色谱-串联质谱分析。结果基于11个(RP/HC- 11p模型)、9个(RP/RA- 9p模型)和14个(RP/非RP- 14p模型)建立的模型,在160个检测到的肽中,RP组能够完全区分HC组、RA组和非RP组(HC + RA)。几乎所有组成这些模型的15种鉴定的歧视性肽都是与凝血相关的蛋白质片段。四个模型,每个模型由RP/nonRP-14P模型(模型RP/nonRP-4P-2, -10, -11和-38)的10个鉴定肽中的4个组成,在应用于验证集(测试集和GPA组)时提供≥70.0%的灵敏度和特异性(AUROC, 0.779-0.815)。值得注意的是,RP/nonRP-4P-2模型在验证集中提供了83.3%的灵敏度和71.7%的特异性(AUROC, 0.802)。结论血清肽可作为鉴别RP的候选生物标志物,并可能参与RP的病理生理过程。
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引用次数: 0
Sex-based estimation of biological variation in plasma-free amino acid concentrations among healthy adults 健康成人血浆游离氨基酸浓度生物学变异的性别估计
IF 3.1 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-04-30 DOI: 10.1016/j.jmsacl.2025.04.010
Müjgan Ercan , Emiş Deniz Akbulut , Ayşen Caniklioğlu , Esra Fırat Oğuz , Yakup Dülgeroğlu , Esin Avcı , Şerif Ercan

Introduction

Free amino acid (FAA) analysis plays a crucial role in diagnosing and monitoring inborn errors of metabolism, assessing nutritional status, and identifying metabolic imbalances associated with various diseases. This study aimed to provide updated biological variation (BV) data to support the reliable clinical application of FAA concentrations in plasma samples, utilizing LC-MS/MS.

Materials and methods

Venous blood was collected from 22 healthy Turkish adults (9 men and 13 women) over approximately nine weeks. Plasma FAAs were measured in duplicate. BV estimates with 95 % confidence intervals were determined using nested ANOVA for the entire study group and sex-stratified subgroups, following analysis of outliers, normality, steady-state conditions, and variance homogeneity.

Results

Within-subject variation (CVI) and between-subject variation (CVG) estimates ranged from 9.5 % to 32.5 % and 8.6 % to 50.0 %, respectively. The estimated CVI values for essential amino acids were significantly lower than those for non-essential amino acids (P = 0.03). For most plasma FAAs, no significant differences in CVI (except for alanine, arginine, glutamic acid, and threonine) or CVG were observed between sexes. However, differences in the indices of individuality were noted between men and women for some plasma FAAs.

Conclusions

This Biological Variation Data Critical Appraisal Checklist-compliant study provides the first updated BV data for plasma FAAs. The significant variation observed in CVI estimates is hypothesized to result from differences in the metabolic regulation of essential versus non-essential amino acids. The sex-stratified indices obtained in this study will aid in the appropriate application of population-based reference intervals for plasma FAA assessment.
游离氨基酸(FAA)分析在诊断和监测先天性代谢错误、评估营养状况和识别与各种疾病相关的代谢失衡方面起着至关重要的作用。本研究旨在利用LC-MS/MS提供最新的生物变异(BV)数据,为血浆样品中FAA浓度的可靠临床应用提供支持。材料和方法在大约9周的时间内采集22名健康土耳其成年人(9名男性和13名女性)的静脉血。血浆FAAs一式两份测定。在分析了异常值、正态性、稳态条件和方差齐性之后,对整个研究组和按性别分层的亚组使用嵌套方差分析确定了95%置信区间的BV估计值。结果受试者内变异(CVI)和受试者间变异(CVG)估计值分别为9.5% ~ 32.5%和8.6% ~ 50.0%。必需氨基酸的CVI估计值显著低于非必需氨基酸(P = 0.03)。对于大多数血浆FAAs, CVI(除了丙氨酸、精氨酸、谷氨酸和苏氨酸)或CVG在两性之间没有显著差异。然而,在一些血浆FAAs中,男性和女性的个性指标存在差异。结论本研究符合生物变异数据关键评估清单,首次提供了血浆FAAs的最新BV数据。在CVI估计中观察到的显著差异被假设为必需氨基酸与非必需氨基酸代谢调节的差异。本研究中获得的性别分层指数将有助于适当应用基于人群的血浆FAA评估参考区间。
{"title":"Sex-based estimation of biological variation in plasma-free amino acid concentrations among healthy adults","authors":"Müjgan Ercan ,&nbsp;Emiş Deniz Akbulut ,&nbsp;Ayşen Caniklioğlu ,&nbsp;Esra Fırat Oğuz ,&nbsp;Yakup Dülgeroğlu ,&nbsp;Esin Avcı ,&nbsp;Şerif Ercan","doi":"10.1016/j.jmsacl.2025.04.010","DOIUrl":"10.1016/j.jmsacl.2025.04.010","url":null,"abstract":"<div><h3>Introduction</h3><div>Free amino acid (FAA) analysis plays a crucial role in diagnosing and monitoring inborn errors of metabolism, assessing nutritional status, and identifying metabolic imbalances associated with various diseases. This study aimed to provide updated biological variation (BV) data to support the reliable clinical application of FAA concentrations in plasma samples, utilizing LC-MS/MS.</div></div><div><h3>Materials and methods</h3><div>Venous blood was collected from 22 healthy Turkish adults (9 men and 13 women) over approximately nine weeks. Plasma FAAs were measured in duplicate. BV estimates with 95 % confidence intervals were determined using nested ANOVA for the entire study group and sex-stratified subgroups, following analysis of outliers, normality, steady-state conditions, and variance homogeneity.</div></div><div><h3>Results</h3><div>Within-subject variation (CV<sub>I</sub>) and between-subject variation (CV<sub>G</sub>) estimates ranged from 9.5 % to 32.5 % and 8.6 % to 50.0 %, respectively. The estimated CV<sub>I</sub> values for essential amino acids were significantly lower than those for non-essential amino acids (<em>P</em> = <em>0.03</em>). For most plasma FAAs, no significant differences in CV<sub>I</sub> (except for alanine, arginine, glutamic acid, and threonine) or CV<sub>G</sub> were observed between sexes. However, differences in the indices of individuality were noted between men and women for some plasma FAAs.</div></div><div><h3>Conclusions</h3><div>This Biological Variation Data Critical Appraisal Checklist-compliant study provides the first updated BV data for plasma FAAs. The significant variation observed in CV<sub>I</sub> estimates is hypothesized to result from differences in the metabolic regulation of essential versus non-essential amino acids. The sex-stratified indices obtained in this study will aid in the appropriate application of population-based reference intervals for plasma FAA assessment.</div></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"37 ","pages":"Pages 1-8"},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Definitive urine drug testing in emergency medicine: Recreational and psychiatric drug findings 急诊医学的最终尿检:娱乐性和精神性药物的发现
IF 3.1 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-04-23 DOI: 10.1016/j.jmsacl.2025.04.008
Thomas G. Rosano , S.M.Touhidul Islam , John M. Rumberger , Robert M. Konetchy Jr. , Michelle Wood , Joseph A. Sorce , Karl A. Robstad , Heather Long

Introduction

Clinical management of drug-related emergency department (ED) visits relies on available history, toxidrome findings and drug screening. In this study, definitive drug testing is used to assess ED drug prevalence and immunoassay drug screening performance.

Methods

Definitive testing for 116 drugs and metabolites was performed on urine from 400 ED patients, with comparison to immunoassay drug screening.

Results

Definitive testing resulted in 1,350 drug findings with prevalent use of nicotine (63%), cocaine (34%), ∆9 tetrahydrocannabinol (34%), fentanyl (17%), morphine or heroin (11%) and methamphetamine (6%). Forty percent of patients were also positive for antidepressants and 24% positive for antipsychotics. Significant patterns of co-drug use were found for cocaine, fentanyl, morphine and nicotine. Multi-serotonergic drug use was frequent, suggesting a risk for serotonin syndrome. Immunoassay performance showed high false negative rates for benzodiazepines (40%), amphetamines (38%), barbiturates (33%), opiates (25%), methadone (20%) and cocaine (16%), along with inaccuracy in phencyclidine detection. Immunoassay missed 890 of the 1,350 drug findings by definitive testing, due to either high cutoff thresholds or limited testing scope.

Discussion

A high prevalence of drugs use by ED patients is evidenced with frequent co-use of illicit and therapeutic drugs and with potential for unrecognized multi-serotonergic drug interactions. This study also shows the limitations of immunoassay drug testing in both scope and sensitivity, with a high rate of undetected drug use.

Conclusion

The study provides evidence-based support for recommended implementation of definitive drug testing in emergency medicine as a guide to clinical management in drug-related ED visits.
药物相关急诊科(ED)就诊的临床管理依赖于现有病史、毒副反应结果和药物筛查。在这项研究中,明确的药物测试是用来评估ED药物流行和免疫测定药物筛选性能。方法对400例ED患者的尿液进行116种药物和代谢物的明确检测,并与免疫法药物筛选进行比较。结果最终检测出1350种药物,其中普遍使用尼古丁(63%)、可卡因(34%)、∆9四氢大麻酚(34%)、芬太尼(17%)、吗啡或海洛因(11%)和甲基苯丙胺(6%)。40%的患者抗抑郁药物检测呈阳性,24%的患者抗精神病药物检测呈阳性。在可卡因、芬太尼、吗啡和尼古丁中发现了显著的联合用药模式。多血清素能药物的使用频繁,提示患血清素综合征的风险。免疫分析结果显示,苯二氮卓类药物(40%)、安非他明(38%)、巴比妥类药物(33%)、阿片类药物(25%)、美沙酮(20%)和可卡因(16%)的假阴性率较高,苯环利定检测不准确。在1350种药物的最终检测中,由于阈值过高或检测范围有限,免疫分析法遗漏了890种。ED患者药物使用的高流行率表明,经常同时使用非法药物和治疗药物,并且可能存在未被识别的多种血清素能药物相互作用。本研究还显示了免疫测定药物检测在范围和灵敏度上的局限性,未被检测到的药物使用率很高。结论本研究为建议在急诊医学中实施明确的药物检测作为药物相关急诊科就诊的临床管理指南提供了循证支持。
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引用次数: 0
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Journal of Mass Spectrometry and Advances in the Clinical Lab
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