RADIOIMMUNOASSAY AND GAS-CHROMATOGRAPHY MASS-SPECTROMETRY FOR A NOVELANTIGLAUCOMA MEDICATION OF A PROSTAGLANDIN DERIVATIVE, S-1033, IN PLASMA

A radioimmunoassay (RIA) and a gas chromatographic/mass spectrometric (GC/MS) method for a new antiglaucoma medicament, the prostaglandin de rivative sodium (5Z,9 alpha,11 alpha,13E)-9,11-dihydroxyprosta-5,13-di enoate (S-1033), in human and rabbit plasma were investigated. For a c ompetitive RIA, antisera from rabbit and radioiodine-labeled S-1033 we re prepared by immunizing a conjugate of S-1033 with bovine serum albu min and by the Bolton and Hunter method, respectively, Pretreatment by C-18 solid-phase extraction (SPE) for rabbit plasma sample and furthe r purification by high-performance liquid chromatography (HPLC) for hu man plasma samples followed by the RIA (SPE/RIA and HPLC/RIA, respecti vely) were developed. The assay recoveries of SPE/RIA and HPLC/RIA wer e both excellent and the limits of quantitation were 320 and 10 pg ml( -1), respectively. GC/MS for plasma samples after solid-phase extracti on and thin-layer chromatographic purification was also developed usin g deuterium-labeled S-1033 as internal standard. The limit of quantita tion was 100 pg ml(-1) in human or rabbit plasma. Rabbit plasma sample s after administration of this drug were measured by SPE/RIA and GC/MS and the assay results from both methods agreed well. The SPE/RIA, HPL C/RIA and GC/MS assay methods were suitable for measuring samples from preclinical studies, clincial studies and cross-validation, respectiv ely.