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Research ArticleArticle

Metabolites of Hexamethyldisiloxane and Decamethylcyclopentasiloxane in Fischer 344 Rat Urine—A Comparison of a Linear and a Cyclic Siloxane

Sudarsanan Varaprath, Joan M. McMahon and Kathleen P. Plotzke
Drug Metabolism and Disposition February 2003, 31 (2) 206-214; DOI: https://doi.org/10.1124/dmd.31.2.206
Sudarsanan Varaprath
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Joan M. McMahon
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Kathleen P. Plotzke
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Abstract

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.

Footnotes

  • ↵2 HPLC and GC-MS of standards were not included in this manuscript. They will be available upon request.

  • ↵3 HPLC and GC-MS of standards were not included in this manuscript. They will be available upon request. Also, only the GC-MS data of those metabolites not available in the literature are given here.

  • Abbreviations used are::
    MM
    (HMDS) hexamethyldisiloxane
    D5
    decamethylcyclopentasiloxane
    D4
    octamethylcyclotetrasiloxane
    HPLC
    high performance liquid chromatography
    GC
    gas chromatography
    MS
    mass spectrometry
    THF
    tetrahydrofuran
    BSTFA
    bis(trimethylsilyl)trifluoroacetamide
    BF3-THF
    borontrifluoride-THF
    SPE
    saline/phosphate/EDTA
    and the following abbreviations are based on General Electric's siloxane notation [Hurd (1946)]
    M, Me3SiO1/2
    D
    −Me2SiO2/2
    and D′
    MeRSiO2/2, where R is any group as indicated
    • Received April 11, 2002.
    • Accepted November 4, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 31 (2)
Drug Metabolism and Disposition
Vol. 31, Issue 2
1 Feb 2003
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Research ArticleArticle

Metabolites of Hexamethyldisiloxane and Decamethylcyclopentasiloxane in Fischer 344 Rat Urine—A Comparison of a Linear and a Cyclic Siloxane

Sudarsanan Varaprath, Joan M. McMahon and Kathleen P. Plotzke
Drug Metabolism and Disposition February 1, 2003, 31 (2) 206-214; DOI: https://doi.org/10.1124/dmd.31.2.206

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Research ArticleArticle

Metabolites of Hexamethyldisiloxane and Decamethylcyclopentasiloxane in Fischer 344 Rat Urine—A Comparison of a Linear and a Cyclic Siloxane

Sudarsanan Varaprath, Joan M. McMahon and Kathleen P. Plotzke
Drug Metabolism and Disposition February 1, 2003, 31 (2) 206-214; DOI: https://doi.org/10.1124/dmd.31.2.206
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