Establishment of a Charge Reversal Derivatization Strategy to Improve the Ionization Efficiency of Limaprost and Investigation of the Fragmentation Patterns of Limaprost Derivatives Via Exclusive Neutral Loss and Survival Yield Method

  • Dong Sun
  • Xiangjun Meng
  • Tianming Ren
  • John Paul Fawcett
  • Hualu Wang
  • Jingkai Gu
Research Article


Sensitivity is generally an issue in bioassays of prostaglandins and their synthetic analogs due to their extremely low concentration in vivo. To improve the ionization efficiency of limaprost, an oral prostaglandin E1 (PGE1) synthetic analog, we investigated a charge reversal derivatization strategy in electrospray ionization mass spectrometry (ESI-MS). We established that the cholamine derivative exhibits much greater signal intensity in the positive-ion mode compared with limaprost in the negative ion mode. Collision-induced dissociation (CID) involved exclusive neutral mass loss and positive charge migration to form stable cationic product ions with the positive charge on the limaprost residue rather than on the modifying group. This has the effect of maintaining the efficiency and specificity of multiple reaction monitoring (MRM) and avoiding cross talk. CID fragmentation patterns of other limaprost derivatives allowed us to relate the dissociation tendency of different neutral leaving groups to an internal energy distribution scale based on the survival yield method. Knowledge of the energy involved in the production of stabilized positive ions will potentially assist the selection of suitable derivatization reagents for the analysis of a wide variety of lipid acids.

Graphical Abstract


Charge reversal Derivatization of limaprost Positive charge migration Exclusive neutral loss Survival yield method 


Funding Information

The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (Grant Nos. 81430087 and 81673396) and the Science and Technology Major Specialized Projects for “significant new drugs creation” of the 13th 5-year plan (2017ZX09101001).


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Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  1. 1.Research Center for Drug MetabolismJilin UniversityChangchunPeople’s Republic of China
  2. 2.School of Life SciencesJilin UniversityChangchunPeople’s Republic of China
  3. 3.School of PharmacyUniversity of OtagoDunedinNew Zealand
  4. 4.Beijing Xiuzheng Innovation Medicine Research Institute Co. Ltd.BeijingPeople’s Republic of China

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