UHPLC-MS/MS profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseases
Abstract Bile acids (BAs) are synthesized in the liver and can mediate homeostasis and various metabolism processes in the human body. Their levels in the gastrointestinal tract are closely related to various gastrointestinal diseases. In particular, farnesoid X receptor activated by free BAs is ass...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2020-06-01
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| Series: | Journal of Analytical Science and Technology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40543-020-00218-6 |
| _version_ | 1818720518956646400 |
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| author | Wonwoong Lee Jinhee Um Keon-hee Ko Yong Chan Lee Bong Chul Chung Jongki Hong |
| author_facet | Wonwoong Lee Jinhee Um Keon-hee Ko Yong Chan Lee Bong Chul Chung Jongki Hong |
| author_sort | Wonwoong Lee |
| collection | DOAJ |
| description | Abstract Bile acids (BAs) are synthesized in the liver and can mediate homeostasis and various metabolism processes in the human body. Their levels in the gastrointestinal tract are closely related to various gastrointestinal diseases. In particular, farnesoid X receptor activated by free BAs is associated with overexpression of histidine decarboxylase in tumorigenesis. Therefore, comprehensive profiling of histamine (HIST), histidine (His), and BAs in biological samples can provide insight into the pathological mechanisms of gastrointestinal diseases. However, development of an analytical platform to profile HIST, His, and BAs in biological samples has several challenges such as highly different polarities between acidic and basic targets, low physiological concentrations of analytes, and high matrix interference of biological samples. In this study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method combined with serial derivatization was developed to simultaneously determine HIST, His, and 5 BAs (cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and lithocholic acid) in human gastric fluid. In serial derivatization, benzoyl chloride (BzCl) and N,N-dimethylethylenediamine (DMED) were used to selectively derivatize amino and carboxyl groups of analytes, respectively. After serial derivatization, all target derivatives were determined using a reverse-phase C18 LC column and positive multiple reaction monitoring (MRM) mode, with reasonable chromatographic separation and sensitive MS detection. To accurately quantify target metabolites, 7 stable isotope-labeled internal standards were used. The MS/MS spectra of DMED and Bz derivatives exhibited specific fragments via loss of a neutral molecule (dimethylamine; 45 Da) and inductive cleavage (benzoyl; m/z 105) from protonated molecules, enabling selection of appropriate MRM transition ions for selective and sensitive detection. The developed method was validated with respect to limits of detection and quantification, linearity, precision, accuracy, stability, and matrix effect. The established method was successfully applied to human gastric fluid samples. This method provides reliable quantification of HIST, His, and BAs in human gastric fluid and will be helpful to understand pathophysiological mechanisms of gastric diseases. |
| first_indexed | 2024-12-17T20:24:07Z |
| format | Article |
| id | doaj.art-9bb9767758ce4e6ab84c8b37f2a4e489 |
| institution | Directory Open Access Journal |
| issn | 2093-3371 |
| language | English |
| last_indexed | 2024-12-17T20:24:07Z |
| publishDate | 2020-06-01 |
| publisher | SpringerOpen |
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| series | Journal of Analytical Science and Technology |
| spelling | doaj.art-9bb9767758ce4e6ab84c8b37f2a4e4892022-12-21T21:33:51ZengSpringerOpenJournal of Analytical Science and Technology2093-33712020-06-0111111110.1186/s40543-020-00218-6UHPLC-MS/MS profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseasesWonwoong Lee0Jinhee Um1Keon-hee Ko2Yong Chan Lee3Bong Chul Chung4Jongki Hong5College of Pharmacy, Kyung Hee UniversityCollege of Pharmacy, Kyung Hee UniversityCollege of Pharmacy, Kyung Hee UniversityDepartment of Internal Medicine, Institute of Gastroenterology, Yonsei University College of MedicineMolecular Recognition Research Center, Korea Institute of Science and TechnologyCollege of Pharmacy, Kyung Hee UniversityAbstract Bile acids (BAs) are synthesized in the liver and can mediate homeostasis and various metabolism processes in the human body. Their levels in the gastrointestinal tract are closely related to various gastrointestinal diseases. In particular, farnesoid X receptor activated by free BAs is associated with overexpression of histidine decarboxylase in tumorigenesis. Therefore, comprehensive profiling of histamine (HIST), histidine (His), and BAs in biological samples can provide insight into the pathological mechanisms of gastrointestinal diseases. However, development of an analytical platform to profile HIST, His, and BAs in biological samples has several challenges such as highly different polarities between acidic and basic targets, low physiological concentrations of analytes, and high matrix interference of biological samples. In this study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method combined with serial derivatization was developed to simultaneously determine HIST, His, and 5 BAs (cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and lithocholic acid) in human gastric fluid. In serial derivatization, benzoyl chloride (BzCl) and N,N-dimethylethylenediamine (DMED) were used to selectively derivatize amino and carboxyl groups of analytes, respectively. After serial derivatization, all target derivatives were determined using a reverse-phase C18 LC column and positive multiple reaction monitoring (MRM) mode, with reasonable chromatographic separation and sensitive MS detection. To accurately quantify target metabolites, 7 stable isotope-labeled internal standards were used. The MS/MS spectra of DMED and Bz derivatives exhibited specific fragments via loss of a neutral molecule (dimethylamine; 45 Da) and inductive cleavage (benzoyl; m/z 105) from protonated molecules, enabling selection of appropriate MRM transition ions for selective and sensitive detection. The developed method was validated with respect to limits of detection and quantification, linearity, precision, accuracy, stability, and matrix effect. The established method was successfully applied to human gastric fluid samples. This method provides reliable quantification of HIST, His, and BAs in human gastric fluid and will be helpful to understand pathophysiological mechanisms of gastric diseases.http://link.springer.com/article/10.1186/s40543-020-00218-6Bile acidsHistidineHistamineUHPLC-MS/MS-MRMProfiling analysisSerial derivatization |
| spellingShingle | Wonwoong Lee Jinhee Um Keon-hee Ko Yong Chan Lee Bong Chul Chung Jongki Hong UHPLC-MS/MS profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseases Journal of Analytical Science and Technology Bile acids Histidine Histamine UHPLC-MS/MS-MRM Profiling analysis Serial derivatization |
| title | UHPLC-MS/MS profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseases |
| title_full | UHPLC-MS/MS profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseases |
| title_fullStr | UHPLC-MS/MS profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseases |
| title_full_unstemmed | UHPLC-MS/MS profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseases |
| title_short | UHPLC-MS/MS profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseases |
| title_sort | uhplc ms ms profiling of histidine and bile acid metabolism in human gastric fluid for diagnosis of gastric diseases |
| topic | Bile acids Histidine Histamine UHPLC-MS/MS-MRM Profiling analysis Serial derivatization |
| url | http://link.springer.com/article/10.1186/s40543-020-00218-6 |
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