Vol. 31, Issue 2, 206-214, February 2003

Metabolites of Hexamethyldisiloxane and Decamethylcyclopentasiloxane in Fischer 344 Rat UrineA Comparison of a Linear and a Cyclic Siloxane

Sudarsanan Varaprath, Joan M. McMahon, and Kathleen P. Plotzke

Dow Corning Corporation, Midland, Michigan

Hexamethyldisiloxane (MM or HMDS) and decamethylcylclopentasiloxane (D₅) are examples of a linear and a cyclic siloxane, respectively. These volatile low molecular weight siloxanes are of significant commercial importance. To aid in the pharmacokinetic investigations, major metabolites of MM and D₅ were identified in urine collected from Fischer (F-344) rats administered [¹⁴C]MM and [¹⁴C]D₅ orally and via intravenous injection. The metabolite profiles were obtained using a high-pressure liquid chromatography (HPLC) system equipped with a radioisotope detector. The metabolite elution was carried out on a C₁₈ column using an acetonitrile/water mobile phase. The structural assignments were based on GC-MS analysis of the tetrahydrofuran extract of urine containing the metabolites. Some of the metabolites in the extracts were first protected with trimethylsilyl groups prior to GC-MS analysis using bis(trimethylsiloxy)trifluoroacetamide or highly purified hexamethyldisiloxane. The structures were also confirmed by comparisons with synthetic ¹⁴C-labeled metabolite standards. The following are among the major metabolites identified in the case of MM: Me₂Si(OH)₂, HOMe₂SiCH₂OH, HOCH₂Me₂SiOSiMe₂CH₂OH, HOMe₂SiOSiMe₂CH₂-OH, HOCH₂Me₂SiOSiMe₃, and Me₃SiOH. The metabolites of D₅ are as follows: Me₂Si(OH)₂, MeSi(OH)₃, MeSi(OH)₂OSi(OH)₃, MeSi(OH)₂OSi(OH)₂Me, MeSi(OH)₂OSi(OH)Me₂, Me₂Si(OH)OSi(OH)Me₂, Me₂Si(OH)OSiMe₂OSi(OH)Me₂, nonamethylcyclopentasiloxanol, and hydroxymethylnonamethylcyclopentasiloxane. No parent MM or D₅ was present in urine The presence of certain metabolites such as HOMe₂SiCH₂OH and Me₂Si(OH)₂ in MM and D₅, respectively, clearly established the occurrence of demethylation at the silicon-methyl bonds. Metabolites of the linear siloxane are structurally different from that obtained for cyclic siloxane except for the commonly present Me₂Si(OH)₂. Mechanistic pathways for the formation of the metabolites were proposed.