Blessborn Daniel, Romsing Susanne, Bergqvist Yngve, Lindegardh Niklas
Dalarna University College, Borlange, Sweden.
Bioanalysis. 2010 Nov;2(11):1839-47. doi: 10.4155/bio.10.147.
More parasites are becoming resistant to antimalarial drugs, and in many areas a change in first-line drug treatment is necessary. The aim of the developed assay is to help determine drug use in these areas and also to be a complement to interviewing patients, which will increase reliability of surveys.
This assay detects quinine, mefloquine, sulfadoxine, pyrimethamine, lumefantrine, chloroquine and its metabolite desethylchloroquine in a 100-µl dried blood spot. Most of the drugs also have long half-lives that make them detectable at least 7 days after administration. The drugs are extracted from the dried blood spot with sequential extraction (due to the big differences in physicochemical properties), solid-phase extraction is used as sample clean-up and separation is performed with gradient-LC with MS ion-trap detection.
Detection limits (S/N > 5:1) at 50 ng/ml or better were achieved for all drugs except lumefantrine (200 ng/ml), and thus can be used to determine patient compliance. A major advantage of using the ion-trap MS it that it will be possible to go back into the data and look for other drugs as needed.
越来越多的疟原虫对抗疟药物产生耐药性,在许多地区有必要改变一线药物治疗方案。所开发的检测方法旨在帮助确定这些地区的药物使用情况,同时作为对患者访谈的补充,从而提高调查的可靠性。
该检测方法可在100微升干血斑中检测奎宁、甲氟喹、磺胺多辛、乙胺嘧啶、本芴醇、氯喹及其代谢物去乙基氯喹。大多数药物还具有较长的半衰期,使得在给药后至少7天仍可检测到它们。通过顺序萃取(由于物理化学性质差异很大)从干血斑中提取药物,使用固相萃取进行样品净化,并采用梯度液相色谱-质谱离子阱检测进行分离。
除本芴醇(200纳克/毫升)外,所有药物的检测限(信噪比>5:1)均达到50纳克/毫升或更佳,因此可用于确定患者的依从性。使用离子阱质谱的一个主要优点是可以根据需要回溯数据并寻找其他药物。