کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
7626524 1494580 2018 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Semi-quantitative measurement of the antimalarial lumefantrine from untreated dried blood spots using LC-MS/MS
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Semi-quantitative measurement of the antimalarial lumefantrine from untreated dried blood spots using LC-MS/MS
چکیده انگلیسی
Study of the clinical effects of combination therapy for malaria is aided by the ability to measure concentrations of individual partner drugs. Existing methods for measurement of the antimalarial drug lumefantrine (LF) in dried blood spots (DBS) on filter paper rely on chemical pretreatment of the paper to facilitate drug elution. However, in the absence of pretreatment, DBS may still offer some utility for semi-quantitative measurements and pharmacokinetic-pharmacodynamic (PK-PD) analyses. We present a method for semi-quantitation of LF in DBS on untreated filter paper using liquid chromatography tandem mass spectrometry. Optimal recovery was achieved by extraction with acetone-water-formic acid (90:5:5). The range of quantitation was 100-20,000 ng/ml. Mean intra- and inter-day accuracy values were 86.6% (coefficient of variation [CV]: 10.1%) and 91.8% (CV: 16.1%), therefore we propose the assay as semi-quantitative. Clinical application was demonstrated in exploratory PK-PD analyses of a drug efficacy trial of artemether-lumefantrine in children with uncomplicated falciparum malaria using post-treatment day 7 samples, parasite clearance times estimated from serial blood smears, and recurrence of malaria out to 35 days. The median day 7 concentration among children (n = 71) was 111 ng/ml (interquartile range: 100-194 ng/ml). We used a truncated calibration curve of 100-5000 ng/ml for calculations due to low observed concentrations. Calculations using the full calibration curve yielded similar values (+1% avg. deviation). Controlling for participant age, sex, and parasite burden, each log increase in LF day 7 concentration corresponded to a decrease of 7.1 h in mean parasite clearance time (95% confidence interval: 0.1-14.3 h, P = 0.05). A nested case-control study of participants (n = 18) with and without recurrent malaria showed mean post-treatment day 7 concentrations of 181 ng/ml and 235 ng/ml, respectively, but the difference was not significant (P = 0.64). A method for semi-quantitation of LF from post-treatment day 7 collections of DBS on untreated filter paper demonstrated clinical application in exploratory PK-PD analyses of parasite clearance and reinfection. Use of DBS will endure in certain study settings by virtue of their ease of collection and resilience. Their utility should continue to be explored as our instruments gain in sensitivity and as clinical pharmacology inquiries are pursued to the field.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 155, 5 June 2018, Pages 241-246
نویسندگان
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