Determination of lumefantrine in small-volume human plasma by LC-MS/MS: using a deuterated lumefantrine to overcome matrix effect and ionization saturation

Bioanalysis. 2012 Jan;4(2):157-66. doi: 10.4155/bio.11.303.

Abstract

Background: To support pediatric study, a method to determine lumefantrine (LF) with small sample volume is needed. Matrix effect (ME) is a daunting issue in LF quantification in human plasma with LC-MS/MS.

Results: Here we report an LC-MS/MS method with a deuterated LF as the internal standard (IS). Plasma sample (25 µl) was acidified with 5% formic acid prior to extraction with ethyl acetate. The recovery was over 80%. The absolute ME was within the range of 100 ± 8% for both LF and the IS, but cumulative ME was observed via large variation of IS signal. The cumulative ME and ionization saturation were overcome with the co-eluting LF-D(9) as the IS. The linear range of calibration curve was 50-20,000 ng/ml.

Conclusion: ME and ionization saturation was overcome with a deuterated IS. The method utilized a small sample volume, suitable for pediatric study with capillary tube blood collection method.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / blood*
  • Calibration
  • Chromatography, Liquid / methods*
  • Ethanolamines / blood*
  • Fluorenes / blood*
  • Humans
  • Lumefantrine
  • Reference Standards
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Tandem Mass Spectrometry / methods*

Substances

  • Antimalarials
  • Ethanolamines
  • Fluorenes
  • Lumefantrine