Zuluaga-Idárraga Lina, Yepes-Jiménez Natalia, López-Córdoba Carlos, Blair-Trujillo Silvia
Grupo Malaria, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Medellín, Colombia.
J Pharm Biomed Anal. 2014 Jul;95:200-6. doi: 10.1016/j.jpba.2014.03.006. Epub 2014 Mar 12.
One of the most important aspects regarding the therapeutic efficacy of antimalarials is its quantification in biologic fluids. The detection and measurement of antimalarial drug levels is important for demonstrating (1) adequate absorption of the drug being given, (2) compliance in taking the full regimen required for treatment and (3) the level of drug in the blood at any time during the test period that parasites reappear. There is a lack of validated methods that simultaneously quantify different antimalarials administered at the same time, such as the use of chloroquine (CQ) and primaquine (PQ) in infections caused by Plasmodium vivax. In this study, a bioanalytical method was validated for the simultaneous quantification of primaquine (PQ), chloroquine (CQ) and desethylchloroquine (DSCQ) in human plasma using liquid-liquid extraction and high performance liquid chromatography with a diode array detector (HPLC-DAD). The PQ was evaluated over a concentration range of 100-3000 nM and the CQ and DSCQ was evaluated over a concentration range of 20-2000 nM. The selectivity of the method was verified by checking for interference by commonly used antimalarials and plasma samples. The accuracy and precision of the method was assessed for drugs spiked into human plasma and recoveries of 83.7%, 92.3%, and 76.5% were obtained for CQ, DSCQ, and PQ, respectively. The applicability of this method was also demonstrated with blood samples from patients with vivax malaria that received combination CQ plus PQ treatment. The simultaneous detection and accurate measurement of CQ, DSCQ, and PQ levels in human plasma provides an important and economical method for validating and monitoring sensitivity/resistance of P. vivax to more common treatment regimen.
抗疟药治疗效果的最重要方面之一是在生物体液中的定量分析。抗疟药物水平的检测和测量对于证明以下几点很重要：（1）所给药物的充分吸收；（2）遵循治疗所需的完整疗程；（3）在测试期间寄生虫再次出现的任何时间点血液中的药物水平。目前缺乏能够同时定量分析同时使用的不同抗疟药的经过验证的方法，例如在间日疟原虫感染中使用氯喹（CQ）和伯氨喹（PQ）的情况。在本研究中，建立了一种生物分析方法，用于通过液-液萃取和配备二极管阵列检测器的高效液相色谱法（HPLC-DAD）同时定量分析人血浆中的伯氨喹（PQ）、氯喹（CQ）和去乙基氯喹（DSCQ）。PQ的评估浓度范围为100 - 3000 nM，CQ和DSCQ的评估浓度范围为20 - 2000 nM。通过检查常用抗疟药和血浆样本的干扰来验证该方法的选择性。对添加到人血浆中的药物评估了该方法的准确性和精密度，CQ、DSCQ和PQ的回收率分别为83.7%、92.3%和76.5%。还通过接受CQ加PQ联合治疗的间日疟患者的血样证明了该方法的适用性。同时检测和准确测量人血浆中CQ、DSCQ和PQ的水平为验证和监测间日疟原虫对更常见治疗方案的敏感性/耐药性提供了一种重要且经济的方法。
