Biosynthesis, characterisation and direct high-performance liquid chromatographic analysis of gemfibrozil 1-O-beta-acylglucuronide.
Gemfibrozil 1-O-beta-acylglucuronide was purified from the urine of a volunteer administered gemfibrozil, and an isocratic reversed-phase HPLC method was developed for its direct measurement. Quantitation of gemfibrozil and gemfibrozil 1-O-beta-acylglucuronide was carried out from plasma, following extraction from acidified specimens into ethyl acetate, on a 5-microns CN reversed-phase column with a mobile phase (pH 3.5) containing acetonitrile, tetrabutylammonium sulphate and distilled water, using fluorescence detection at 284 nm excitation and 316 nm emission. Calibration curves were linear for both compounds over a concentration range of 0.1 to 40 mg/l, with intra-assay coefficients of variation < 5% at concentrations of 20.0, 2.0 and 0.2 mg/l, and inter-assay coefficients of variation < 10%. No degradation of gemfibrozil 1-O-beta-acylglucuronide was detected as a result of the analytical procedure. However, a preliminary application of the method indicates that gemfibrozil acylglucuronide is chemically unstable undergoing intra-molecular rearrangement and hydrolysis under physiological conditions.
Sallustio
B C
BC
Department of Clinical Pharmacology, Queen Elizabeth Hospital, Woodville, Australia.
Fairchild
B A
BA
D002851:Chromatography, High Pressure Liquid / Q000706:statistics & numerical data; D002855:Chromatography, Thin Layer; D004355:Drug Stability; D015248:Gemfibrozil / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005965:Glucuronates / Q000097:blood / Q000652:urine*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011786:Quality Control
D005965:Glucuronates; C094370:gemfibrozil 1-O-acylglucuronide; D015248:Gemfibrozil