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Pharmaceutisch Weekblad

, Volume 14, Issue 3, pp 83–87 | Cite as

Direct measurement of probenecid and its glucuronide conjugate by means of high pressure liquid chromatography in plasma and urine of humans

  • T. B. Vree
  • E. W. J. Beneken Kolmer
Articles

Abstract

Probenecid with its phase-I metabolites, and phase-II glucuronide conjugate can be analysed by a gradient high pressure liquid chromatographic method. Probenecid glucuronide in plasma with pH 7.4 is not stable and declines to 10% of the original value within 6 h (t1/2≈1 h). Probenecid glucuronide is stable in urine with pH 5.0, moderately unstable at pH 6.0 (t1/2≈10 h), and unstable at pH 8.0 (t1/2≈0.5 h). Probenecid glucuronide is stable in water and 0.01 mol/l phosphoric acid in the autosampler of the high pressure liquid chromatograph. The decrease in concentration in water is 5.5% during 9 h and 0% in diluted acid. Probenecid glucuronide and the phase-I metabolites were not detectable in plasma. The main compound in fresh urine is the phase-II conjugate probenecid glucuronide (62% of a 500 mg dose); the phase-I metabolites are present and only a trace of probenecid is present. The percentage of the dose of the phase-I metabolites varies between 5 and 10, while hardly any probenecid is excreted unchanged (0.33%).

Keywords

Chromatography, high pressure liquid Metabolites Pharmacokinetics Probenecid 

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1992

Authors and Affiliations

  • T. B. Vree
    • 1
  • E. W. J. Beneken Kolmer
    • 2
  1. 1.Department of Clinical Pharmacy and Institute of AnaesthesiologyUniversity Hospital Nijmegen Sint RadboudHB Nijmegenthe Netherlands
  2. 2.Department of Clinical PharmacyUniversity Hospital Nijmegen Sint Radboudthe Netherlands

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