PMID- 31397147 OWN - NLM STAT- MEDLINE DCOM- 20200928 LR - 20200928 IS - 1520-6882 (Electronic) IS - 0003-2700 (Linking) VI - 91 IP - 17 DP - 2019 Sep 3 TI - 4-Plex Chemical Labeling Strategy Based on Cinchona Alkaloid-Derived Primary Amines for the Analysis of Chiral Carboxylic Acids by Liquid Chromatography-Mass Spectrometry. PG - 11440-11446 LID - 10.1021/acs.analchem.9b02909 [doi] AB - Chiral carboxylic acids play important roles in energy metabolism and signal transduction in the human body. These enantiomers usually possess different bioactivities and are also associated with the development of some diseases. Therefore, simultaneous determination of multiple chiral carboxylic acids is vital for study of the pathogenesis of related diseases. However, it is still challenging to simultaneously detect the enantiomers of multiple chiral carboxylic acids in biological samples. Here, we developed a novel 4-plex chemical labeling strategy based on 4 analogues of cinchona alkaloid-derived primary amines (CAPAs) for simultaneous determination of 16 enantiomers of 8 chiral carboxylic acids by liquid chromatography-mass spectrometry (LC-MS). To achieve high-throughput analysis, one CAPA analogue was used to label chiral carboxylic acid standards and served as internal standards (ISs), while the other 3 CAPA analogues were used to label endogenous chiral carboxylic acids in 3 different biological samples. After CAPAs labeling, the 16 chiral carboxylic acid enantiomers could be detected by LC-MS, and their detection sensitivity was greatly enhanced by up to 3 orders of magnitude compared to intact analytes. Further, the developed method for the determination of 16 chiral carboxylic acid enantiomers was validated in human serums and mammalian cells. Finally, the proposed method was applied to the determination of chiral carboxylic acids in the serum samples from type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) patients. We found that 5 chiral carboxylic acid enantiomers in T2DM serum samples and 4 chiral carboxylic acid enantiomers in CRC serum samples exhibited significant change compared to the healthy control (HC). FAU - Zheng, Jie AU - Zheng J AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry , Wuhan University , Wuhan 430072 , People's Republic of China. FAU - Zheng, Shu-Jian AU - Zheng SJ AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry , Wuhan University , Wuhan 430072 , People's Republic of China. FAU - Qi, Chu-Bo AU - Qi CB AD - Department of Pathology , Hubei Cancer Hospital , Wuhan 430079 , People's Republic of China. FAU - Wu, Dong-Mei AU - Wu DM AD - Department of Oncology , Zhongnan Hospital of Wuhan University , Wuhan 430071 , People's Republic of China. FAU - Feng, Yu-Qi AU - Feng YQ AUID- ORCID: 0000-0003-1107-5385 AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry , Wuhan University , Wuhan 430072 , People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190820 PL - United States TA - Anal Chem JT - Analytical chemistry JID - 0370536 RN - 0 (Amines) RN - 0 (Carboxylic Acids) RN - 0 (Cinchona Alkaloids) SB - IM MH - Amines/*chemistry MH - Carboxylic Acids/*analysis/blood/chemistry MH - Case-Control Studies MH - Cells, Cultured MH - Chromatography, Liquid MH - Cinchona Alkaloids/*chemistry MH - Colorectal Neoplasms/blood MH - Diabetes Mellitus, Type 2/blood MH - Humans MH - Mass Spectrometry MH - Staining and Labeling/*methods MH - Stereoisomerism EDAT- 2019/08/10 06:00 MHDA- 2020/09/29 06:00 CRDT- 2019/08/10 06:00 PHST- 2019/08/10 06:00 [pubmed] PHST- 2020/09/29 06:00 [medline] PHST- 2019/08/10 06:00 [entrez] AID - 10.1021/acs.analchem.9b02909 [doi] PST - ppublish SO - Anal Chem. 2019 Sep 3;91(17):11440-11446. doi: 10.1021/acs.analchem.9b02909. Epub 2019 Aug 20.