Gemfibrozil and its oxidative metabolites: quantification of aglycones, acyl glucuronides, and covalent adducts in samples from preclinical and clinical kinetic studies

Hermening A., Grafe A., Baktir G., Mutschler E., Spahn-Langguth H.

JOURNAL OF CHROMATOGRAPHY B, cilt.741, sa.2, ss.129-144, 2000 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 741 Sayı: 2
  • Basım Tarihi: 2000
  • Doi Numarası: 10.1016/s0378-4347(00)00041-4
  • Dergi Adı: JOURNAL OF CHROMATOGRAPHY B
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.129-144
  • İstanbul Üniversitesi Adresli: Hayır

Özet

A gradient reversed-phase HPLC analysis for the direct measurement of gemfibrozil (GEM) and four oxidative metabolites in plasma and urine of humans and in tissue homogenates of rats was developed. The corresponding acyl glucuronides and the covalently bound protein adducts (in protein precipitates) were determined after liberation from the respective conjugates via alkaline hydrolysis. The limits of detection for the covalent adducts in human plasma are: 10 ng ml(-1) (GEM), 20 ng ml(-1) (M1), 0.5 ng ml(-1) (M2, M4), and 5 ng ml(-1) (M3). The method was validated with respect to selectivity, recovery, linearity, precision, and accuracy. It has been applied to the analysis of preclinical and clinical studies. Pharmacokinetic profiles of gemfibrozil, its metabolites, and covalent adducts in human plasma and rat tissue homogenates are given. (C) 2000 Elsevier Science B.V. All rights reserved.