• Differential mobility separation of leukotrienes and protectins.

      Jónasdóttir, Hulda S; Papan, Cyrus; Fabritz, Sebastian; Balas, Laurence; Durand, Thierry; Hardardottir, Ingibjorg; Freysdottir, Jona; Giera, Martin; [ 1 ] Leiden Univ, Med Ctr, Ctr Prote & Metabol, NL-2300 RC Leiden, Netherlands [ 2 ] Leiden Univ, Med Ctr, Dept Rheumatol, NL-2300 RC Leiden, Netherlands [ 3 ] SCIEX Germany GmbH, D-64293 Darmstadt, Germany [ 4 ] Univ Montpellier, IBMM, CNRS, UMR 5247, F-34090 Montpellier, France [ 5 ] Univ Iceland, Sch Hlth Sci, Biomed Ctr, Fac Med, IS-101 Reykjavik, Iceland [ 6 ] Landspitali Natl Univ Iceland, Dept Immunol, IS-101 Reykjavik, Iceland [ 7 ] Landspitali Natl Univ Iceland, Ctr Rheumatol Res, IS-101 Reykjavik, Iceland (Amer Chemical Soc, 2015-05-19)
      Differential mobility spectrometry (DMS) is capable of separating stereoisomeric molecular ions based on their mobility in an oscillating electrical field with an asymmetric waveform. Thus, it is an "orthogonal" technique to chromatography and (tandem) mass spectrometry. Bioactive lipids, particularly of the eicosanoid and docosanoid class feature numerous stereoisomers, which exhibit a highly specific structure-activity relationship. Moreover, the geometry of these compounds also reflects their biochemical origin. Therefore, the unambiguous characterization of related isomers of the eicosanoid and docosanoid classes is of fundamental importance to the understanding of their origin and function in many biological processes. Here we show, that SelexION DMS technology coupled to μLC-MS/MS is capable of differentiating at least five closely related leukotrienes partially coeluting and (almost) unresolvable using LC-MS/MS only. We applied the developed method to the separation of LTB4 and its coeluting isomer 5S,12S-diHETE in murine peritoneal exudate cells, showing that LTB4 is present only after zymosan A injection while its isomer 5S,12S-diHETE is produced after saline (PBS) administration. Additionally, we show that the SelexION technology can also be applied to the separation of PD1 and PDX (10S,17S-diHDHA), two isomeric protectins.