EXTRACTION OF OCTAMETHYLCYCLOTETRASILOXANE AND ITS METABOLITES FROM BIOLOGICAL MATRICES

Octamethylcyclotetrasiloxane (D-4) is an industrial chemical of signif icant commercial importance. It is a key ingredient in a variety of pr oduct formulations and a critical intermediate in the production of si licone polymers. As part of the pharmacokinetic investigation of its d isposition and metabolism, an efficient extraction methodology has bee n developed to recover both the parent D-4 and its metabolites from va rious biological matrices, including blood, plasma, urine, feces, live r, lung, and fat. Of the common organic solvents evaluated (hexane, me thylene chloride, diethylether, chloroform, methylisobutylketone, etc. ), tetrahydrofuran (THF) was demonstrated to be an excellent choice fo r extracting both D-4 and its metabolites. Test samples were either sp iked with C-14-D-4 or obtained from animals administered C-14-D-4 via various exposure routes (inhalation, iv, etc.) and then subjected to T HF extraction. Recoveries of D-4 and its unbound metabolites from plas ma were essentially quantitative in three extractions. Even in a singl e extraction, the recoveries were >90%. Similar results were obtained for other matrices as web. Extraction efficiencies were measured as fo llows: lung, 98.2 +/- 0.3%; liver, 95.4 +/- 0.4%; fat, 99.4 +/- 0.8%; urine, 98.1 +/- 0.2%; feces, 94.1 +/- 0.6%. HPLC profiles obtained bef ore and after extraction were essentially identical, further confirmin g the suitability of THF as an extractant. (C) 1998 Academic Press.