Reactive desorption electrospray ionization linear ion trap mass spectrometry of latest-generation counterfeit antimalarials via noncovalent complex formation
Reactive desorption electrospray ionization linear ion trap mass spectrometry of latest-generation counterfeit antimalarials via noncovalent complex formation
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DOI：
10.1021/ac062205h
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发表时间：
2007-03-01
影响因子：
7.4
通讯作者：
Fernandez, Facundo M.
中科院分区：
文献类型：
--
作者：
Nyadong, Leonard;Green, Michael D.;Fernandez, Facundo M.
解吸电喷雾电离质谱（DESI MS）作为一种强有力的表面表征工具，在户外被广泛接受。除了其成熟的高通量能力外，DESI的一个独特功能是可以利用带电喷雾微滴和表面分子之间的化学反应来增强电离。在这里，我们提出了一个快速筛选青蒿琥酯抗疟药物的反应性DESI的基础上。青蒿琥酯是治疗恶性疟原虫疟疾的一种重要疗法，但青蒿琥酯片剂在东南亚和最近在非洲被大规模假冒。因此，迫切需要更快、更灵敏的筛查测试。拟定的DESI测定是基于溶解在DESI喷雾溶液中的线性烷基胺与暴露在片剂表面的青蒿琥酯分子之间形成稳定的非共价复合物。我们发现，根据胺的类型和浓度，与无试剂DESI相比，可以获得高达170倍的灵敏度增益。己胺（Hex）、十二胺（DDA）和十八胺（ODA）产生具有气相稳定性的质子结合非共价复合物，其稳定性以[M + Hex + H]（+）< [M + DDA + H]（+）< [M + ODA + H]（+）的顺序增加。串联质谱实验表明，复合物的形成发生在青蒿琥酯内酯环内的胺氮和醚样部分之间的氢键。在反应性DESI检测充分表征后，将其应用于最近在东南亚商店和药店购买的一组可疑青蒿琥酯片剂。我们不仅发现这些样品是假冒的，而且还检测出了几种错误的活性成分。特别令人关切的是，在其中一个样品的表面检测到青蒿琥酯的痕迹，我们用标准色谱技术进行了定量。
Desorption electrospray ionization mass spectrometry (DESI MS) is rapidly becoming accepted as a powerful surface characterization tool for a wide variety of samples in the open air. Besides its well-established high-throughput capabilities, a unique feature of DESI is that chemical reactions between the charged spray microdroplets and surface molecules can be exploited to enhance ionization. Here, we present a rapid screening assay for artesunate antimalarials based on reactive DESI. Artesunate is a vital therapy for Plasmodium falciparum malaria, but artesunate tablets have been counterfeited on a very large scale in SE Asia, and more recently in Africa. For this reason, faster and more sensitive screening tests are urgently needed. The proposed DESI assay is based on the formation of stable noncovalent complexes between linear alkylamines dissolved in the DESI spray solution and artesunate molecules exposed on the tablet surface. We found that, depending on amine type and concentration, a sensitivity gain of up to 170x can be obtained, in comparison to reagent-less DESI. Hexylamine (Hex), dodecylamine (DDA), and octadecylamine (ODA) produced proton-bound noncovalent complexes with gas-phase stabilities, increasing in the order [M + Hex + H](+) < [M + DDA + H](+) < [M + ODA + H](+). Tandem MS experiments revealed that complex formation occurred by hydrogen bonding between the amine nitrogen and the ether-like moieties within the artesunate lactone ring. After the reactive DESI assay was fully characterized, it was applied to a set of recently collected suspicious artesunate tablets purchased in shops and pharmacies in SE Asia. Not only did we find that these samples were counterfeits, but we also detected the presence of several wrong active ingredients. Of particular concern was the positive detection of artesunate traces in the surface of one of the samples, which we quantified with standard chromatographic techniques.