Metabolites of hexamethyldisiloxane and decamethylcyclopentasiloxane in Fischer 344 rat urine--a comparison of a linear and a cyclic siloxane.
Hexamethyldisiloxane (MM or HMDS) and decamethylcylclopentasiloxane (D(5)) 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 D(5) were identified in urine collected from Fischer (F-344) rats administered [(14)C]MM and [(14)C]D(5) 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 C(18) 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 (14)C-labeled metabolite standards. The following are among the major metabolites identified in the case of MM: Me(2)Si(OH)(2), HOMe(2)SiCH(2)OH, HOCH(2)Me(2)SiOSiMe(2)CH(2)OH, HOMe(2)SiOSiMe(2)CH(2)-OH, HOCH(2)Me(2)SiOSiMe(3), and Me(3)SiOH. The metabolites of D(5) are as follows: Me(2)Si(OH)(2), MeSi(OH)(3), MeSi(OH)(2)OSi(OH)(3), MeSi(OH)(2)OSi(OH)(2)Me, MeSi(OH)(2)OSi(OH)Me(2), Me(2)Si(OH)OSi(OH)Me(2), Me(2)Si(OH)OSiMe(2)OSi(OH)Me(2), nonamethylcyclopentasiloxanol, and hydroxymethylnonamethylcyclopentasiloxane. No parent MM or D(5) was present in urine The presence of certain metabolites such as HOMe(2)SiCH(2)OH and Me(2)Si(OH)(2) in MM and D(5), 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 Me(2)Si(OH)(2). Mechanistic pathways for the formation of the metabolites were proposed.
Varaprath
Sudarsanan
S
Dow Corning Corporation, 220 W. Salzburg Road, Mail Code CO30101, Auburn, MI 48666-0994, USA. sudarsanan.varaprath@dowcorning.com
McMahon
Joan M
JM
Plotzke
Kathleen P
KP
D000818:Animals; D005260:Female; D015394:Molecular Structure; D051381:Rats; D011916:Rats, Inbred F344; D012833:Siloxanes / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D014556:Urine / Q000737:chemistry / Q000502:physiology
D012833:Siloxanes; C114768:decamethylcyclopentasiloxane; C015917:hexamethyldisiloxane