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Identification of Phase I and Phase II metabolites of Guanfu base a Hydrochloride in human urine

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Summary

Guanfu base A is a novel arrhythmic drug candidate isolated from the tuber of a traditional Chinese herb. Phase I and Phase II metabolites of Guanfu base A (GFA) Hydrochloride were studied in human urine by means of liquid chromatography mass spectrometry (LC/MSD) and tandem mass spectrometry (MS/MS). For phase I metabolites, Guanfu base I (GFI) was separated by HPLC and identified by comparison with authentic reference for their retention times, molecular ion peaks, fragment ions, and UV spectra. GFA oxide was also indicate to exist in human urine. For phase II metabolites, after human urine was treated either with glucuronidase or sulfatase, GFA occured in the chromatograms. It was suggested that there were GFA glucuronide and GFA sulfate in human urine. Further more, positive molecular ions, m/z 606 and m/z 510, of the two conjugates were detected in human urine by LC/MSD. In addition, characteristic ion of m/z 606 was identified as the precursor ion of m/z 177 [Glucuronic acid+H]+ by using MS/MS. Characteristic ion of m/z 430 [GFA+H]+ was also identified as a product ion of m/z 606 [GFA glucuronide+H]+. It was concluded that there were GFI, GFA oxide, GFA glucuronide and GFA sulfate in human urine.

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Abbreviations

GFA:

guanfu base A

GFI:

guanfu base I

AA:

guanfu alcohol amine

LC/MSD:

liquid chromatography-mass spectrometry

ESI:

electrospray ionization

CID:

collision-induced dissociation

TIC:

total ion chromatogram

MS/MS:

tandem mass spectrometry

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Authors and Affiliations

  1. Department of Clinical Pharmacology, the First Affiliated Hospital of NanJing Medical University, NanJing, People’s Republic of China

    A J. Y.

  2. Department of Phytochemistry, China Pharmaceutical University, NanJing, People’s Republic of China

    Liu J. H.

  3. Center of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, 24 Tong Jia Xiang, 210009, NanJing, P.R. China

    Wang G. J. PhD, Sun J. G., Gu Y. C. & Wu M. S.

Authors
  1. A J. Y.
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  2. Wang G. J. PhD
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  3. Sun J. G.
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  4. Gu Y. C.
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  5. Wu M. S.
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  6. Liu J. H.
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A J. Y., Wang, G.J., Sun, J.G. et al. Identification of Phase I and Phase II metabolites of Guanfu base a Hydrochloride in human urine. European Journal of Drug Metabolism and Pharmacokinetics 28, 265–272 (2003). https://doi.org/10.1007/BF03220178

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  • DOI: https://doi.org/10.1007/BF03220178

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