Simultaneous fast HPLC-MS/MS analysis of drug candidates and hydroxyl metabolites in plasma

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Abstract

A rapid bioanalytical method was evaluated for the simultaneous determination of drug discovery compounds and their potential metabolites in plasma samples within 1 min run time by fast high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS). The fast HPLC-MS/MS system is achieved by using mini-column HPLC coupled to tandem mass spectrometer which is advantageous over regular HPLC-MS/MS systems, such as a shorter chromatographic region of ionization suppression, less solvent consumption and higher throughput. Matrix ionization suppression effect of the test compounds in plasma samples when using fast HPLC-MS/MS method was examined by a post-column infusion technique. In the described example, the proposed approach has been successfully employed to determine the plasma concentration of the test compound and its hydroxyl metabolite (M+16) in monkey in the low ng/ml region. The monkey pharmacokinetic results obtained by the proposed fast HPLC-MS/MS method were in good agreement within 20% error with those obtained by the regular HPLC-MS/MS method based on the same sample preparation procedure. © 2003 Elsevier B.V. All rights reserved.

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Hsieh, Y., Brisson, J. M., Wang, G., Ng, K., & Korfmacher, W. A. (2003). Simultaneous fast HPLC-MS/MS analysis of drug candidates and hydroxyl metabolites in plasma. Journal of Pharmaceutical and Biomedical Analysis, 33(2), 251–261. https://doi.org/10.1016/S0731-7085(03)00351-0

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