Chemical isotope labeling-assisted liquid chromatography-mass spectrometry enables sensitive and accurate determination of dipeptides and tripeptides in complex biological samples

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外文摘要：Small peptides have attracted increasing attention for their unique features and diverse biological func-tions.Achieving rapid separation and accurate quantification,however,remains a challenge because of their low abundance and the co-existence of numerous structural isomers.In this study,we developed a novel approach using isotope chemical labeling for ultrasensitive determination of di/tripeptides in bi-ological samples.We successfully synthesized a novel derivatization reagent,4-(2-(ethoxymethylene)-3-oxobutanamido)-N,N,N-trimethylbenzenaminium iodide(EOTMBA)as well as its deuterium-labeled iso-tope reagent(d3-EOTMBA).A total of 97 small peptides,including 89 dipeptides and 8 tripeptides,could be completely derivatized in methanol within 1.5 h at 60 ℃.After EOTMBA labeling,analysis of these di/tripeptides were achieved within 22 min by LC-MS/MS analysis.The method demonstrated 86.3％-113％accuracy and the limit of quantification ranged from 0.25 fmol/L to 5nmol/L.Using this method,we achieved ultrasensitive and accurate quantification of di/tripeptides in 147 plasma,49 urine and 46 bile samples obtained from healthy individuals and patients with biliary tract diseases.The iden-tified differential di/tripeptide biomarker panels showed promising diagnostic performance for patients with biliary tract cancer with area under the receiver operating curve values from 0.870 to 0.996.Further-more,this method was successfully applied to quantify di/tripeptides in the extract of an animal-derived traditional Chinese medicine,Eupolyphaga sinensis Walker.These findings highlight the possible appli-cation of the analytical method in clinics and for the purposes of quality control of traditional Chinese medicines.

外文关键词：

Di/tripeptidesChemical derivatizationIsotope labelingLiquid chromatography tandem mass spectrometryBiliary tract cancer

作者：

Feng-Qing Huang、Yu Wang、Ji-Wen Wang、Dai Yang、Shi-Lei Wang、Yuan-Ming Fan、Raphael N.Alolga、Lian-Wen Qi

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作者单位：

State Key Laboratory of Natural Medicines,School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China

Clinical Metabolomics Center,China Pharmaceutical University,Nanjing 211198,China

Department of General Surgery,Zhongshan Hospital,Fudan University,Shanghai 200032,China

College of Chinese Materia Medica and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong 030619,China

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出版年：

2024

DOI：

10.1016/j.cclet.2024.109670

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCD

影响因子：0.771

ISSN：1001-8417

年,卷(期)：2024.35(11)