Measurement of plasma probucol levels by high-performance liquid chromatography.
An improved assay for measuring plasma levels of probucol using reversed-phase high-performance liquid chromatography has been developed and used to measure probucol in cholesterol-fed rabbits. The sample was extracted with iso-octane, reconstituted in acetonitrile and was analysed using a Hypersil ODS column with a mobile phase consisting of acetonitrile-water (96:4, v/v). Detection was carried out using ultraviolet absorption at 241 nm. The lower detection limit for plasma probucol was 0.5 micrograms/ml. Inter-assay and intra-assay coefficients of variation were 1.8-4.8% and 1.6-3.3%, respectively. The method was applied to measurements of probucol in plasma from rabbits receiving a diet containing 1% probucol and 2% cholesterol for five weeks. Probucol levels at five weeks were significantly higher in the animals receiving concomitant cholesterol, and were close to the steady-state values predicted from the one week measurements. Also, the plasma probucol levels were positively correlated with total plasma cholesterol (r = 0.87, p < 0.001). The results indicate that bioavailability of probucol is dependent on the lipid content of the diet.
Nourooz-Zadeh
J
J
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, Charterhouse Square, London, UK.
Gopaul
N K
NK
Forster
L A
LA
Ferns
G A
GA
Anggård
E E
EE
D000818:Animals; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D011341:Probucol / Q000097:blood* / Q000493:pharmacokinetics; D011817:Rabbits; D012680:Sensitivity and Specificity
D002784:Cholesterol; D011341:Probucol