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GC-MS Analysis of the 8-Aminoquinoline Antimalarial [NPC1161] and its Carboxy Metabolite in Plasma and Red Blood Cells of Primates

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Abstract

This study describes a novel and simple GC-MS procedure developed for the determination of the concentration of the 8-aminoquinoline antimalarial agent NPC1161 and its carboxy metabolite in plasma and red blood cells. Preliminary pharmacokinetic data were generated for the two enantiomers of NPC1161 in monkeys. NPC1161, the internal standard, and desalkyl metabolite were converted to their mono-heptafluorobutyrates, while the carboxy metabolite underwent an intramolecular cyclization to give a lactam product. The calibration curves were linear ranging from 10 to 2,000 ng mL−1. The developed GC-MS method is sensitive and reproducible for measuring blood level of this antimalarial drug.

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Acknowledgment

This work was supported in part by the NIH, SBIR Grants No.1R41 AI42406–01A1 and 2R42 AI42406–02.

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Authors and Affiliations

  1. ElSohly Laboratories, Incorporated, 5 Industrial Park Drive, Oxford, MS, 38655, USA

    M. A. ElSohly & W. Gul

  2. National Center for Natural Products Research (NCNPR), School of Pharmacy, University of Mississippi, University, MS, 38677, USA

    M. A. ElSohly, W. Gul, N. P. D. Nanayakkara, A. M. Clark, S. Khan & L. A. Walker

  3. Philip Morris USA, 615 Maury Street, Richmond, VA, 23224, USA

    S. Feng

  4. Tulane Regional Primate Research Center, Tulane University Health Sciences Center, Covington, LA, 70433, USA

    F. B. Cogswell

  5. Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS, 38677, USA

    L. A. Walker

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  1. M. A. ElSohly
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  2. W. Gul
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  3. S. Feng
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  4. N. P. D. Nanayakkara
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  5. A. M. Clark
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  6. S. Khan
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  7. F. B. Cogswell
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  8. L. A. Walker
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Correspondence to M. A. ElSohly.

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ElSohly, M.A., Gul, W., Feng, S. et al. GC-MS Analysis of the 8-Aminoquinoline Antimalarial [NPC1161] and its Carboxy Metabolite in Plasma and Red Blood Cells of Primates. Chroma 64, 199–205 (2006). https://doi.org/10.1365/s10337-006-0015-7

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  • DOI: https://doi.org/10.1365/s10337-006-0015-7

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