Marino M T, Peggins J O, Brewer T G
Department of Pharmacology, Walter Reed Army Institute of Research, Washington, DC 20307.
J Chromatogr. 1993 Jul 2;616(2):338-43. doi: 10.1016/0378-4347(93)80405-s.
WR 242511 (or I) is a new compound of the 8-aminoquinoline class designed to replace primaquine for the treatment of malaria. In order to perform preclinical and clinical testing, an assay was needed to determine drug levels in plasma samples. A simple and reliable reversed-phase high-performance liquid chromatographic (HPLC) method for the measurement of I in plasma using oxidative electrochemical detection is described. A 250-microliters plasma sample containing WR 256408 (or II) as internal standard was extracted with tert.-butyl methyl ether-2-propanol. A 25-microliters aliquot of the extractant was used for HPLC analysis. The mobile phase was 50:50 acetonitrile-sodium acetate (50 mM, pH 6) with 1 mM EDTA. Compounds I and II were separated within 10 min. The limit of detection for I was 10 ng/ml (plasma) with a recovery around 72%. The method was validated in a dog experiment where levels were followed for 48 h. The method is sensitive and robust and can be used for routine drug analysis during pharmacokinetic studies.
WR 242511（或I）是一种新型8-氨基喹啉类化合物，旨在替代伯氨喹用于疟疾治疗。为了进行临床前和临床试验，需要一种测定血浆样本中药物水平的方法。本文描述了一种使用氧化电化学检测法测定血浆中I的简单可靠的反相高效液相色谱（HPLC）方法。以含有WR 256408（或II）作为内标的250微升血浆样本用叔丁基甲醚-2-丙醇进行萃取。取25微升萃取剂等分试样用于HPLC分析。流动相为含1 mM乙二胺四乙酸的50:50乙腈-醋酸钠（50 mM，pH 6）。化合物I和II在10分钟内分离。I的检测限为10 ng/ml（血浆），回收率约为72%。该方法在一项犬实验中得到验证，在该实验中对血药浓度进行了48小时的监测。该方法灵敏且稳健，可用于药代动力学研究期间的常规药物分析。
