Determination of Lumefantrine in Small-Volume Human Plasma By Lc–MS/MS: Using A Deuterated Lumefantrine to Overcome Matrix Effect And Ionization Saturation

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 as the IS. The linear signal. The cumulative ME and ionization saturation were overcome with the co-eluting LF-D9 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.

Antiretroviral Agents and Prevention of Malaria in HIV-Infected Ugandan Children

“…10 Lumefantrine levels were measured in 25-µl samples as described previously. 11 The interassay and intraassay precision (percentage coefficient of variation) was 5.3 to 6.1% and 2.2 to 10%, respectively. The interassay and intra-assay accuracy was 103.5 to 107.1% and 99.5 to 109.7%, respectively.…”

Development and validation of a LC–MS/MS method for the quantitation of lumefantrine in mouse whole blood and plasma

“…The developed method uses 20 l of mouse WB or plasma which is the smallest sample volume as compared to other published methods [10][11][12][13][14][15]. The protein precipitation extraction method was robust, efficient and provided high recovery rates for LF in both WB and plasma.…”

“…), ensures that the method is robust and reproducible for analysing samples of unknown concentrations. There are five published LC-MS/MS methods for the quantification of LF in human plasma and one for the quantification of LF in rat plasma [10][11][12][13][14][15]. There seems to be no LC-MS/MS methods for the quantification of LF in mouse WB or plasma.…”

“…The use of a stable isotope labeled IS may prove invaluable to overcome ion suppression and ensure the reproducibility of this quantitative method. The use of a stable isotope labeled LF as the IS was reported, previously, to eliminate the influence of matrix effects and ionization saturation when quantitating LF in human plasma [15].…”

Determination of The Antimalarial Drug Piperaquine in Small Volume Pediatric Plasma Samples by LC–MS/MS

“…It will likely become more popular if coupled with a sensitive analytical method requiring less than 50 µl sample volume or dried blood spot. We previously developed a method to measure lumefantrine in small volume capillary plasma and applied it to field studies [22,23]. The method reported here was applied to venous plasma samples collected previously to simply confirm feasibility in plasma.…”