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

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 mu l) 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.