LC Method for the Determination of NPC1161, Primaquine and their Metabolites in Various Biological Systems |
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Authors: | B. Avula L. M. Tripathi S. I. Khan B. L. Tekwani D. Nanayakkara W. Gul M. A. ElSohly I. A. Khan |
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Affiliation: | (1) National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, Mississippi, MS, USA;(2) Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, Mississippi, MS 38677, USA;(3) ElSohly Laboratories, Incorporated, 5 Industrial Park Drive, Oxford, Mississippi, 38655, USA |
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Abstract: | NPC1161 is an 8-aminoquinoline anti-malarial analog, which has a favorable toxicity profile relative to primaquine and other 8-aminoquinolines. High-performance liquid chromatographic method was developed for the determination of NPC1161, primaquine and their metabolites in biological samples in order to facilitate metabolic and pharmacokinetic studies. The method includes extraction of the unchanged drugs and their metabolites from the biological samples. Separation was achieved by reversed-phase chromatography on a C18 column with water–acetonitrile both containing 0.025% trifluoroacetic acid as the mobile phase. Recoveries of NPC1161 and its metabolites were greater than 60% in various biological samples tested. No interference with the components of the biological material was observed. The detector response was linear with concentrations of NPC1161 and its metabolites (desalkyl NPC1161 and carboxy NPC1161) in the ranges from 0.5 to 80.0, 0.4–60.0 and 0.4–70.0 μg mL−1, respectively. A mass spectrometry coupled with electrospray ionization (ESI) interface method is described for the identification of NPC1161 and its metabolites in biological samples. This method involved the use of the [M + H]+ions of NPC1161, C3 analog (internal std. for the assay), desalkyl NPC1161 and carboxy NPC1161 at m/z 434, 406, 349 and 449 in the positive ion mode with extractive ion monitoring (EIM). This method will have an important application in pharmacokinetic studies of NPC1161 and in understanding the mechanism of metabolism of this novel 8-aminoquinoline analog in more detail. |
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Keywords: | Column liquid chromatography Anti-malarial drugs Metabolites in biological samples Primaquine |
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