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

Drug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA 94110, USA.
Bioanalysis (Impact Factor: 3.25). 01/2012; 4(2):157-66. DOI: 10.4155/bio.11.303
Source: PubMed

ABSTRACT 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.
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.
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.

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