PMID- 31472699 OWN - NLM STAT- MEDLINE DCOM- 20191216 LR - 20191217 IS - 1873-4324 (Electronic) IS - 0003-2670 (Linking) VI - 1082 DP - 2019 Nov 15 TI - Simultaneous quantitative analysis of multiple sphingoid bases by stable isotope labeling assisted liquid chromatography-mass spectrometry. PG - 106-115 LID - S0003-2670(19)30822-0 [pii] LID - 10.1016/j.aca.2019.07.016 [doi] AB - Sphingoid bases (SBs) are one of important components of cell membranes, playing important roles in cellular biology. Meanwhile, SBs are associated with various metabolic diseases such as Type 2 Diabetes mellitus (T2DM). Therefore, simultaneous quantitation of multiple SBs in biological samples could provide crucial information for uncovering underlying mechanisms of SBs related functions and diseases. However, existing methods are difficult to achieve simultaneous quantitation for multiple SBs due to the lack of isotope internal standards (ISs) of corresponding SBs. In the current study, we developed a highly sensitive method for the simultaneous detection of 26 SBs in biological samples by stable isotope labeling coupled with ultra-high performance liquid chromatography tandem mass spectrometry (SIL-UHPLC-MS/MS) analysis. In this respect, a pair of isotope labeling reagents, 3-(N, N-dimethylamino)propyl isothiocyanate (DMPI) and d(4)-3-(N, N-dimethylamino)propyl isothiocyanate (d(4)-DMPI), were synthesized and utilized to label SBs in biological samples and SB standards, respectively. The d(4)-DMPI labeled SB standards were used as ISs to calibrate quantitation deviation in MS analysis from the biological matrix. Using the developed method, we successfully quantitated 19 SBs in cells, 20 SBs in mice feces and 18 SBs in human serum samples. Three C17-SBs used as ISs in many reported works were even found in all prepared samples. In summary, the developed SIL-UHPLC-MS/MS analysis was demonstrated to be a promising method for the simultaneous determination of multiple SBs, which could facilitate the investigation of cellular function of SBs and pathogenesis of related diseases. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. 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, PR China. 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, PR China. FAU - Xiao, Hua-Ming AU - Xiao HM AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, PR China. FAU - Wu, Dong-Mei AU - Wu DM AD - Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China. FAU - Feng, Yu-Qi AU - Feng YQ AD - Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, PR China. Electronic address: yqfeng@whu.edu.cn. LA - eng PT - Journal Article DEP - 20190709 PL - Netherlands TA - Anal Chim Acta JT - Analytica chimica acta JID - 0370534 RN - 0 (Biomarkers) RN - 0 (Isothiocyanates) RN - 0 (Sphingolipids) RN - AR09D82C7G (Deuterium) SB - IM MH - Alzheimer Disease/diagnosis MH - Animals MH - Biomarkers/blood/chemistry MH - Cell Line, Tumor MH - Chromatography, High Pressure Liquid/*methods MH - Deuterium MH - Diabetes Mellitus, Type 2/diagnosis MH - Feces/chemistry MH - Humans MH - Isothiocyanates/chemistry MH - Isotope Labeling/methods MH - Limit of Detection MH - Mice MH - Sphingolipids/*blood/chemistry MH - Tandem Mass Spectrometry/*methods OTO - NOTNLM OT - Alzheimer's disease OT - Cells OT - Liquid chromatography-tandem mass spectrometry OT - Sphingoid bases OT - Stable isotope labeling OT - T2DM EDAT- 2019/09/02 06:00 MHDA- 2019/12/18 06:00 CRDT- 2019/09/02 06:00 PHST- 2019/05/10 00:00 [received] PHST- 2019/07/05 00:00 [revised] PHST- 2019/07/07 00:00 [accepted] PHST- 2019/09/02 06:00 [entrez] PHST- 2019/09/02 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] AID - S0003-2670(19)30822-0 [pii] AID - 10.1016/j.aca.2019.07.016 [doi] PST - ppublish SO - Anal Chim Acta. 2019 Nov 15;1082:106-115. doi: 10.1016/j.aca.2019.07.016. Epub 2019 Jul 9.