Huang Liusheng, Li Xiaohua, Marzan Florence, Lizak Patricia S, Aweeka Francesca T
Drug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA 94110, USA.
Bioanalysis. 2012 Jan;4(2):157-66. doi: 10.4155/bio.11.303.
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.
为支持儿科研究，需要一种能够用少量样本测定卤泛群（LF）的方法。在采用液相色谱-串联质谱法（LC-MS/MS）对人血浆中的LF进行定量分析时，基质效应（ME）是一个棘手的问题。
在此，我们报道一种以氘代LF作为内标（IS）的LC-MS/MS方法。血浆样本（25μl）在用乙酸乙酯萃取前用5%甲酸酸化。回收率超过80%。LF和IS的绝对基质效应均在100±8%范围内，但通过IS信号的大幅变化观察到累积基质效应。使用共洗脱的LF-D(9)作为IS克服了累积基质效应和电离饱和。校准曲线的线性范围为50-20,000 ng/ml。
使用氘代内标克服了基质效应和电离饱和。该方法使用少量样本，适用于采用毛细管采血法的儿科研究。
