Laboratório de Controle de Qualidade de Medicamentos e Cosméticos, Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Brazil.
Laboratório de Controle de Qualidade de Medicamentos e Cosméticos, Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Brazil.
J Pharm Biomed Anal. 2019 Feb 20;165:304-314. doi: 10.1016/j.jpba.2018.12.021. Epub 2018 Dec 13.
Malaria is a worldwide health issue, with 216 million cases reported in 2016. Due to the widespread resistance of Plasmodium falciparum to conventional drugs, the first line treatment recommended by World Health Organization for uncomplicated malaria is artemisinin-based combined therapy (ACT), which combines two drugs with different mechanisms of action. The association of artemether and lumefantrine is the most common ACT used in the clinical practice. However, there have been reports of clinical artemisinin and derivatives partial resistance, which is defined as delayed parasite clearance. In this context, the monitoring of drug concentration in biological matrices is essential to evaluate treatment response, the need of dose adjustment and the occurrence of dose dependent adverse effects. Furthermore, it is also important for pharmacokinetic studies and in the development of generic and similar drugs. Determination of antimalarial drugs in biological matrices requires a sample pre-treatment, which involves drug extraction from the matrix and analyte concentration. The most used techniques are protein precipitation (PP), liquid-liquid extraction (LLE) and solid phase extraction (SPE). Subsequently, a liquid chromatography step is usually applied to separate interferences that could be extracted along with the analyte. Finally, the analytes are detected employing techniques that must be selective and sensitive, since the analyte might be present in trace levels. The most used approach for detection is tandem mass spectrometry (MS-MS), but ultraviolet (UV) is also employed in several studies. In this article, a review of the scientific peer-review literature dealing with validated quantitative analysis of artemether and/or lumefantrine in biological matrices, from 2000 to 2018, is presented.
疟疾是一个全球性的健康问题，2016 年报告的病例有 2.16 亿例。由于恶性疟原虫对传统药物广泛耐药，世界卫生组织推荐的治疗无并发症疟疾的一线药物是青蒿素为基础的联合疗法（ACT），它结合了两种具有不同作用机制的药物。青蒿琥酯和本芴醇的联合是临床实践中最常用的 ACT。然而，已经有报道称青蒿素和衍生物出现部分耐药性，这被定义为寄生虫清除延迟。在这种情况下，监测生物基质中的药物浓度对于评估治疗反应、调整剂量的需要以及发生剂量依赖性不良反应至关重要。此外，对于药代动力学研究和开发仿制药和类似药物也很重要。在生物基质中测定抗疟药物需要对样品进行预处理，这涉及从基质中提取药物和分析物的浓缩。最常用的技术是蛋白质沉淀（PP）、液-液萃取（LLE）和固相萃取（SPE）。随后，通常应用液相色谱步骤来分离可能与分析物一起提取的干扰物。最后，采用选择性和灵敏性高的技术来检测分析物，因为分析物可能存在于痕量水平。最常用的检测方法是串联质谱法（MS-MS），但在几项研究中也使用了紫外（UV）。本文综述了 2000 年至 2018 年期间在科学同行评议文献中关于青蒿素和/或本芴醇在生物基质中定量分析的验证研究。
