Radioimmunoassay for a novel lignan-related hypocholesterolemic agent, S-8921, in human plasma after high-performance liquid chromatography purification and in human urine after immunoaffinity extraction.
The novel compound methyl-1-(3,4-dimethoxyphenyl)-3-(3-ethylvaleryl)-4-hydroxy-6,7,8- trimethoxy-2-naphthoate (S-8921) has hypocholesterolemic activity in animals and is expected to exhibit a similar activity in human. Reversed-phase high-performance liquid chromatography (HPLC) separation followed by radioimmunoassay (RIA) for human plasma samples (HPLC-RIA) and immunoaffinity extraction (IAE) followed by RIA for human urine samples (IAE-RIA) were developed for investigation of S-8921 behavior in clinical studies. For the RIA, antisera from rabbit and a radioiodine-labelled S-8921 were prepared by immunizing a conjugate of S-8921 with bovine serum albumin and by the Bolton and Hunter method, respectively. HPLC-RIA using a semi-micro column was very sensitive, that is a 0.05 ng/ml limit of quantitation in human plasma, and specific for unchanged form of S-8921. IAE-RIA using a centrifugal filtration tube completely eliminated the matrix effect of human urine, and was very feasible. The limit of quantitation was 0.10 ng/ml. RIA detection following HPLC or IAE proved to be very useful for the pharmaceutical analysis of extremely low drug concentrations in body fluids.
Kominami
G
G
Shionogi Research Laboratories, Shionogi and Co., Ltd., Osaka, Japan.
Ueda
A
A
Sakai
K
K
Misaki
A
A
D000924:Anticholesteremic Agents; D002498:Centrifugation; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007158:Immunologic Techniques; D007700:Kinetics; D009284:Naphthols / Q000097:blood* / Q000652:urine*; D011863:Radioimmunoassay
D000924:Anticholesteremic Agents; D009284:Naphthols; C106517:S 8921