Müller D, Blaschke G
Institute of Pharmaceutical Chemistry, University of Münster, Germany.
J Chromatogr Sci. 2000 Oct;38(10):435-40. doi: 10.1093/chromsci/38.10.435.
A sensitive assay for the determination of chloroquine (Clq) and its pharmacologically active metabolite deethyl chloroquine in plasma by capillary electrophoresis (CE) is developed. Plasma levels of drug and metabolite are measured using HeCd laser-induced fluorescence (LIF) detection over a range of three orders of magnitude from 2 to 1000 ng/mL after liquid-liquid extraction. A limit of detection of 0.5 ng/mL is achieved. Validation of the method yields intra- and interday precision data within the limits of 10% (20% at limit of quantitation) and intra- and interday accuracy data greater than 6% throughout the whole working range. The method is applied for the drug monitoring of patients treated with Clq. Based upon this assay, two enantioselective CE-LIF methods for Clq and its main metabolite are developed. Mixtures of substituted gamma-cyclodextrins are used as chiral selectors. A baseline separation of the enantiomers of both analytes in one run is achieved in less than 11 min (method A) and less than 9 min (method B), respectively. Hydroxychloroquine is used as the internal standard for both methods.
开发了一种通过毛细管电泳（CE）测定血浆中氯喹（Clq）及其药理活性代谢物去乙基氯喹的灵敏分析方法。在液-液萃取后，使用氦镉激光诱导荧光（LIF）检测在2至1000 ng/mL的三个数量级范围内测量药物和代谢物的血浆水平。实现了0.5 ng/mL的检测限。该方法的验证产生了日内和日间精密度数据，在整个工作范围内，日内和日间精密度数据在10%（定量限为20%）以内，日内和日间准确度数据大于6%。该方法应用于接受氯喹治疗患者的药物监测。基于此分析方法，开发了两种用于氯喹及其主要代谢物的对映体选择性CE-LIF方法。使用取代的γ-环糊精混合物作为手性选择剂。两种分析物的对映体在一次运行中分别在不到11分钟（方法A）和不到9分钟（方法B）内实现基线分离。两种方法均使用羟氯喹作为内标。
