PMID- 32475388 OWN - NLM STAT- MEDLINE DCOM- 20210111 LR - 20210111 IS - 1873-4324 (Electronic) IS - 0003-2670 (Linking) VI - 1120 DP - 2020 Jul 11 TI - Quantitative profiling of eicosanoids derived from n-6 and n-3 polyunsaturated fatty acids by twin derivatization strategy combined with LC-MS/MS in patients with type 2 diabetes mellitus. PG - 24-35 LID - S0003-2670(20)30491-8 [pii] LID - 10.1016/j.aca.2020.04.064 [doi] AB - Eicosanoids derived from n-6 and n-3 polyunsaturated fatty acids (PUFAs), serving as important signaling molecules, are implicated in many physiological and pathological processes, including Type 2 diabetes mellitus (T2DM). However, the quantification of endogenous eicosanoids is challenged by high structural similarity, low abundance in biological sample and poor electrospray ionization efficiency. In the current study, a sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quantify 65 eicosanoids derived from n-6 and n-3 PUFAs in plasma samples using twin derivatization strategy with a pair of reagents, 5-(dimethylamino) naphthalene-1-sulfonyl piperazine (Dns-PP) and (diethylamino) naphthalene-1-sulfonyl piperazine (Dens-PP). Dns-PP-derivatized plasma sample was mixed with the equal volume of Dens-PP-derivatized eicosanoid internal standards for LC-MS/MS analysis in multiple reaction monitoring (MRM) mode. After Dns-PP derivatization, the ionization efficiency and separation performance were substantially improved, resulting in the enhanced sensitivity by 446- to 1009-folds compared to intact eicosanoids. The quantitative accuracy determined by twin derivatization method was found to be comparable with stable isotope labeled internal standards (SIL-IS) method. The newly proposed method was successfully employed to quantify the target eicosanoids in plasma samples from healthy controls and the patients with T2DM. N-6 PUFA-derived eicosanoids, PGF2alpha, PGD2, PGE2, PGA2, PGB2, 20-HETE and LTC4, significantly increased in plasma sample of T2DM patients. Oppositely, n-3 PUFA-derived eicosanoids, RvE1, 12(S)-HEPE and RvD1, remarkably decreased. Spearman's correlation analysis indicated the strong correlations between these highlighted eicosanoids and clinical parameters of T2DM. Collectively, the sensitive and reliable eicosanoid quantification method may facilitate to elucidate the characteristics of eicosanoid metabolism and understand the role of eicosanoids in the pathogenesis of T2DM and other diseases. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Xia, Fangbo AU - Xia F AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China. FAU - He, Chengwei AU - He C AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China. FAU - Ren, Meng AU - Ren M AD - Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yanjiang West Road, Guangzhou, Guangdong, China. Electronic address: renmeng80@139.com. FAU - Xu, Feng-Guo AU - Xu FG AD - Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing, Jiangsu, China. Electronic address: fengguoxu@gmail.com. FAU - Wan, Jian-Bo AU - Wan JB AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao SAR, China. Electronic address: jbwan@um.edu.mo. LA - eng PT - Journal Article DEP - 20200428 PL - Netherlands TA - Anal Chim Acta JT - Analytica chimica acta JID - 0370534 RN - 0 (Eicosanoids) RN - 0 (Fatty Acids, Omega-3) RN - 0 (Fatty Acids, Omega-6) SB - IM MH - Chromatography, Liquid MH - Diabetes Mellitus, Type 2/*blood/diagnosis MH - Eicosanoids/*blood/chemistry MH - Fatty Acids, Omega-3/*chemistry MH - Fatty Acids, Omega-6/*chemistry MH - Humans MH - Molecular Structure MH - Tandem Mass Spectrometry OTO - NOTNLM OT - Chemical isotope labeling OT - Eicosanoids OT - LC-MS/MS OT - Quantification OT - Twin derivatization OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/06/02 06:00 MHDA- 2021/01/12 06:00 CRDT- 2020/06/02 06:00 PHST- 2020/03/15 00:00 [received] PHST- 2020/04/07 00:00 [revised] PHST- 2020/04/27 00:00 [accepted] PHST- 2020/06/02 06:00 [entrez] PHST- 2020/06/02 06:00 [pubmed] PHST- 2021/01/12 06:00 [medline] AID - S0003-2670(20)30491-8 [pii] AID - 10.1016/j.aca.2020.04.064 [doi] PST - ppublish SO - Anal Chim Acta. 2020 Jul 11;1120:24-35. doi: 10.1016/j.aca.2020.04.064. Epub 2020 Apr 28.