Identification and elimination of ion suppression in the quantitative analysis of sirolimus in human blood by LC/ESI-MS/MS

Nariyasu Mano, Marina Nozawa, Mayumi Sato, Masaru Mori, Hiroaki Yamaguchi, Katsuhiro Kanda, Makoto Nogami, Junichi Goto, Miki Shimada

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Ion suppression can negatively affect the performance characteristics of LC/ESI-MS/MS based methods, and we wished to identify sources of ion suppression in an assay for quantitating sirolimus in human whole blood. We first compared the peak areas of sirolimus and ascomycin added to human blood samples treated with and without extraction using octadecyl silyl (ODS)-silica gel after protein precipitation, and we found that water-soluble compounds cause the ion suppression for both drugs. Post-column infusion studies indicated that compounds retained in the sample after ODS extraction and protein precipitation caused ion suppression. MS analysis of these compounds suggested they were hydroxyl group-possessing phosphocholines, and this was confirmed using purified lysophosphatidylcholine variants. Therefore, we included a HybridSPE treatment step after the ODS extraction into the preanalytical workflow to remove phosphocholines, and this successfully eliminated the observed ion suppression for determining sirolimus concentration in human whole blood by LC/ESI-MS/MS. Sirolimus is a highly lipophilic molecule, and this study demonstrates the impact that preanalytical extraction and purification steps can have on a laboratory's ability to accurately detect and quantitate this and other lipophilic drugs.

Original languageEnglish
Pages (from-to)968-974
Number of pages7
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Issue number13-14
Publication statusPublished - 2011 Apr 15


  • Electrospray ionization
  • Ion suppression
  • Mass spectrometry
  • Phospholipids
  • Sirolimus

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology


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